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A Study Comparing Ceftazidime-Avibactam Versus Meropenem in Hospitalized Adults With Nosocomial Pneumonia

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ClinicalTrials.gov Identifier: NCT01808092
Recruitment Status : Completed
First Posted : March 11, 2013
Results First Posted : February 3, 2017
Last Update Posted : September 6, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Nosocomial Pneumonia (NP)
Ventilator-associated Pneumonia (VAP)
Interventions Drug: ceftazidim-avibactam (CAZ-AVI, experimental product)
Drug: meropenem (active comparator)
Enrollment 969
Recruitment Details Overall, 879 patients were randomized in this study, from 4 geographic regions. The first patient was enrolled on 13 April 2013 and the last patient last visit was on 07 January 2016. Summary tables exclude 62 patients with moderate/severe renal impairment recruited prior to a protocol amendment to the dose regimen for such patients (MSRIBorig).
Pre-assignment Details The first patient was enrolled on 13 April 2013 and the last patient last vist was on 07 January 2016. Overall, 969 patients were enrolled in this study, 90 of them screen failures.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description 2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Period Title: Overall Study
Started 409 408
Completed 355 363
Not Completed 54 45
Reason Not Completed
Death             39             29
Lost to Follow-up             3             7
Withdrawal by Subject             9             4
Other Eligibility criteria             3             5
Arm/Group Title CAZ-AVI Meropenem Total
Hide Arm/Group Description 2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo Total of all reporting groups
Overall Number of Baseline Participants 405 403 808
Hide Baseline Analysis Population Description
Baseline characteristics analysis is based on safety analysis set: randomized patients who received any amount of study therapy. 9 patients were randomized but not treated.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 405 participants 403 participants 808 participants
61.8  (16.76) 61.7  (17.57) 61.7  (17.16)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 405 participants 403 participants 808 participants
18-45 74 74 148
46-64 124 122 246
65-74 97 95 192
75-90 110 112 222
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 405 participants 403 participants 808 participants
Female
101
  24.9%
105
  26.1%
206
  25.5%
Male
304
  75.1%
298
  73.9%
602
  74.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 405 participants 403 participants 808 participants
Asian 226 217 443
Black/African American 3 2 5
Native Hawaiian/Pacific Islander 0 0 0
Other 5 7 12
White 171 177 348
1.Primary Outcome
Title The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Clinically Modified Intent-to-treat Analysis Set (Co-primary Analyses)
Hide Description The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The clinical modified intent-to-treat (cMITT) included all patients who met the minimum disease criteria and received any amount of study treatment, and had either no baseline pathogens or at least one study-qualifying Gram-negative baseline pathogen.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 356 370
Measure Type: Number
Unit of Measure: participants
Clinical cure 245 270
Clinical failure 79 70
Indeterminate 32 30
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Meropenem
Comments Statistical analysis for the proportion of patients with clinical cure at TOC in cMITT analysis set
Type of Statistical Test Non-Inferiority or Equivalence
Comments The statistical test of NI for the primary efficacy analysis will be performed at the 2.5% 1 sided significance level. This test will be based on the lower limit of a 2-sided 95% confidence interval (CI). Consistent with the protocol, NI will be concluded if the lower limit of the 95% CI is greater than -12.5%.
Statistical Test of Hypothesis P-Value 0.007
Comments P-value for 1-sided test at test of cure (TOC) with a -12.5% non-inferiority margin, i.e. H0: diff <= -12.5%.
Method % Risk Difference (RD)
Comments RD is CAZ-AVI clinical cure rate minus Meropenem clinical cure rate. The CI was calculated by Miettinen and Nurminen method without adjustment.
Method of Estimation Estimation Parameter percentage: units for RD are %
Estimated Value -4.2
Confidence Interval (2-Sided) 95%
-10.76 to 2.46
Estimation Comments [Not Specified]
2.Primary Outcome
Title The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Clinically Evaluable at TOC Analysis Set (Co-primary Analyses)
Hide Description The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The clinically evaluable (CE) analysis set included all patients in the clinical modified intent-to-treat (cMITT) analysis set who met the stringent criteria for clinical evaluation described in the protocol regarding dosing, prior and concomitant medication, evaluation, etc.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 257 270
Measure Type: Number
Unit of Measure: participants
Clinical cure 199 211
Clinical failure 58 59
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CAZ-AVI, Meropenem
Comments Statistical analysis for the proportion of patients with clinical cure at TOC in CE at TOC analysis set
Type of Statistical Test Non-Inferiority or Equivalence
Comments The statistical test of NI for the primary efficacy analysis will be performed at the 2.5% 1 sided significance level. This test will be based on the lower limit of a 2-sided 95% confidence interval (CI). Consistent with the protocol, NI will be concluded if the lower limit of the 95% CI is greater than -12.5%.
Statistical Test of Hypothesis P-Value <0.001
Comments P-value for 1-sided test at test of cure (TOC) with a -12.5% non-inferiority margin, i.e. H0: diff <= -12.5%.
Method % Risk Difference (RD)
Comments RD is CAZ-AVI clinical cure rate minus Meropenem clinical cure rate. The CI was calculated by Miettinen and Nurminen method without adjustment.
Method of Estimation Estimation Parameter percentage: units for RD are %
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-7.86 to 6.39
Estimation Comments [Not Specified]
3.Secondary Outcome
Title The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Microbiologically Modified Intent-to-treat Analysis Set
Hide Description The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 171 184
Measure Type: Number
Unit of Measure: participants
Clinical cure 120 138
Clinical failure 37 34
Indeterminate 14 12
4.Secondary Outcome
Title The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Extended Microbiologically Evaluable Analysis Set
Hide Description The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The extended-ME (EME) analysis set defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture regardless of susceptibility to study agents.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 125 131
Measure Type: Number
Unit of Measure: participants
Clinical cure 96 103
Clinical failure 29 28
5.Secondary Outcome
Title The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Microbiologically Evaluable Analysis Set
Hide Description The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiologically evaluable (ME) analysis sets defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture that is susceptible to both study agents (CAZ-AVI and meropenem).
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 107 118
Measure Type: Number
Unit of Measure: participants
Clinical cure 85 94
Clinical failure 22 24
6.Secondary Outcome
Title The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set
Hide Description The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 171 184
Measure Type: Number
Unit of Measure: participants
Clinical cure 143 161
Clinical failure 23 18
Indeterminate 5 5
7.Secondary Outcome
Title The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Clinically Modified Intent-to-treat Analysis Set
Hide Description The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The clinical modified intent-to-treat (cMITT) included all patients who met the minimum disease criteria and received any amount of study treatment, and had either no baseline pathogens or at least one study-qualifying Gram-negative baseline pathogen.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 356 370
Measure Type: Number
Unit of Measure: participants
Clinical cure 292 309
Clinical failure 50 45
Indeterminate 14 16
8.Secondary Outcome
Title The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Clinically Evaluable Analysis Set
Hide Description The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The clinically evaluable (CE) analysis set included all patients in the clinical modified intent-to-treat (cMITT) analysis set who met the stringent criteria for clinical evaluation described in the protocol regarding dosing, prior and concomitant medication, evaluation, etc.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 291 306
Measure Type: Number
Unit of Measure: participants
Clinical cure 253 268
Clinical failure 38 38
9.Secondary Outcome
Title The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable Analysis Set
Hide Description The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The extended-ME (EME) analysis set defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture regardless of susceptibility to study agents.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 143 151
Measure Type: Number
Unit of Measure: participants
Clinical cure 125 135
Clinical failure 18 16
10.Secondary Outcome
Title The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Microbiologically Evaluable Analysis Set
Hide Description The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiologically evaluable (ME) analysis sets defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture that is susceptible to both study agents (CAZ-AVI and meropenem).
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 122 138
Measure Type: Number
Unit of Measure: participants
Clinical cure 110 126
Clinical failure 12 12
11.Secondary Outcome
Title The Number of Patients With a Favorable Per-patient Microbiologic Response at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 171 184
Measure Type: Number
Unit of Measure: participants
Favorable 128 148
Unfavorable 38 31
Indeterminate 5 5
12.Secondary Outcome
Title The Number of Patients With a Favorable Per-patient Microbiologic Response at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 171 184
Measure Type: Number
Unit of Measure: participants
Favorable 95 118
Unfavorable 64 54
Indeterminate 12 12
13.Secondary Outcome
Title The Number of Patients With a Favorable Per-patient Microbiologic Response at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable at End of Treatment Analysis Set
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The extended-ME (EME) analysis set defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture regardless of susceptibility to study agents.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 143 151
Measure Type: Number
Unit of Measure: participants
Favorable 112 123
Unfavorable 31 28
14.Secondary Outcome
Title The Number of Patients With a Favorable Per-patient Microbiologic Response at Test-of-cure (TOC) Visit in Extended Microbiologically Evaluable at Test-of-cure Analysis Set
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The extended-ME (EME) analysis set defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture regardless of susceptibility to study agents.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 125 131
Measure Type: Number
Unit of Measure: participants
Favorable 80 89
Unfavorable 45 42
15.Secondary Outcome
Title The Number of Patients With a Favorable Per-patient Microbiologic Response at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiologically evaluable (ME) analysis sets defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture that is susceptible to both study agents (CAZ-AVI and meropenem).
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 122 138
Measure Type: Number
Unit of Measure: participants
Favorable 96 112
Unfavorable 26 26
16.Secondary Outcome
Title The Number of Patients With a Favorable Per-patient Microbiologic Response at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiologically evaluable (ME) analysis sets defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture that is susceptible to both study agents (CAZ-AVI and meropenem).
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 107 118
Measure Type: Number
Unit of Measure: participants
Favorable 70 83
Unfavorable 37 35
17.Secondary Outcome
Title The Number of Favorable Per-pathogen Microbiologic Responses at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set at End of Treatment Visit
Hide Description The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen. (pathogens in ≥10 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 171 184
Measure Type: Number
Unit of Measure: participants with favorable responses
Enterobacter aerogenes (n=8, 8) 6 5
Enterobacter cloacae (n=26, 22) 25 20
Escherichia coli (n=17, 20) 15 18
Klebsiella pneumoniae (n=59, 71) 49 65
Proteus mirabilis (n=14, 12) 12 10
Serratia marcescens (n=15, 13) 12 11
Haemophilus influenzae (n=16, 25) 15 25
Pseudomonas aeruginosa (n=58, 47) 33 27
Staphylococcus aureus (n=24, 34) 21 32
18.Secondary Outcome
Title The Number of Favorable Per-pathogen Microbiologic Responses at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable at End of Treatment Analysis Set
Hide Description The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The extended-ME (EME) analysis set defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture regardless of susceptibility to study agents. (pathogens in ≥10 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 143 151
Measure Type: Number
Unit of Measure: participants with favorable responses
Enterobacter aerogenes (n=6, 7) 4 5
Enterobacter cloacae (n=22, 17) 22 17
Escherichia coli (n=14, 18) 13 17
Klebsiella pneumoniae (n=46, 57) 39 53
Proteus mirabilis (n=9, 8) 8 6
Serratia marcescens (n=13, 10) 12 8
Haemophilus influenzae (n=14, 16) 14 16
Pseudomonas aeruginosa (n=50, 41) 30 24
Staphylococcus aureus (n=18, 26) 16 25
19.Secondary Outcome
Title The Number of Favorable Per-pathogen Microbiologic Responses at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set
Hide Description The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiologically evaluable (ME) analysis sets defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture that is susceptible to both study agents (CAZ-AVI and meropenem). (pathogens in ≥10 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 122 138
Measure Type: Number
Unit of Measure: participants with favorable responses
Enterobacter aerogenes (n=6, 7) 4 5
Enterobacter cloacae (n=22, 17) 22 17
Escherichia coli (n=13, 18) 13 17
Klebsiella pneumoniae (n=45, 55) 38 51
Proteus mirabilis (n=9, 8) 8 6
Serratia marcescens (n=13, 10) 12 8
Haemophilus influenzae (n=12, 15) 12 15
Pseudomonas aeruginosa (n=38, 34) 22 19
Staphylococcus aureus (n=16, 23) 14 22
20.Secondary Outcome
Title The Number of Favorable Per-pathogen Microbiologic Responses at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set at Test-of-cure Visit
Hide Description The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen. (pathogens in ≥10 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 171 184
Measure Type: Number
Unit of Measure: participants with favorable responses
Enterobacter aerogenes (n=8, 8) 5 5
Enterobacter cloacae (n=26, 22) 21 13
Escherichia coli (n=17, 20) 13 16
Klebsiella pneumoniae (n=59, 71) 37 53
Proteus mirabilis (n=14, 12) 11 8
Serratia marcescens (n=15, 13) 10 8
Haemophilus influenzae (n=16, 25) 14 23
Pseudomonas aeruginosa (n=58, 47) 22 18
Staphylococcus aureus (n=24, 34) 11 25
21.Secondary Outcome
Title The Number of Favorable Per-pathogen Microbiologic Responses at Test-of-cure (TOC) Visit in Extended Microbiologically Evaluable at Test-of-cure Analysis Set
Hide Description The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The extended-ME (EME) analysis set defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture regardless of susceptibility to study agents. (pathogens in ≥10 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 125 131
Measure Type: Number
Unit of Measure: participants with favorable responses
Enterobacter aerogenes (n=6, 5) 5 3
Enterobacter cloacae (n=21, 11) 18 7
Escherichia coli (n=11, 18) 10 16
Klebsiella pneumoniae (n=37, 49) 29 39
Proteus mirabilis (n=11, 8) 9 6
Serratia marcescens (n=12, 8) 9 5
Haemophilus influenzae (n=11, 13) 11 12
Pseudomonas aeruginosa (n=42, 35) 18 14
Staphylococcus aureus (n=14, 22) 5 17
22.Secondary Outcome
Title The Number of Favorable Per-pathogen Microbiologic Responses at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set
Hide Description The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiologically evaluable (ME) analysis sets defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture that is susceptible to both study agents (CAZ-AVI and meropenem). (pathogens in ≥10 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 107 118
Measure Type: Number
Unit of Measure: participants with favorable responses
Enterobacter aerogenes (n=6, 5) 5 3
Enterobacter cloacae (n=21, 11) 18 7
Escherichia coli (n=10, 18) 10 16
Klebsiella pneumoniae (n=37, 47) 29 38
Proteus mirabilis (n=11, 8) 9 6
Serratia marcescens (n=12, 8) 9 5
Haemophilus influenzae (n=9, 12) 9 11
Pseudomonas aeruginosa (n=31, 28) 13 12
Staphylococcus aureus (n=13, 19) 4 15
23.Secondary Outcome
Title The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Clinically Modified Intent-to-treat Analysis Set at End of Treatment Visit
Hide Description The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen. (pathogens in ≥5 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 171 184
Measure Type: Number
Unit of Measure: participants
All (n=45, 54) 40 45
Enterobacteriaceae (n=34, 41) 32 33
Enterobacter aerogenes (n=4, 2) 3 2
Enterobacter cloacae (n=6, 6) 6 4
Escherichia coli (n=6, 5) 5 3
Klebsiella pneumoniae (n=20, 30) 20 26
Gram- pathogens not Enterobacteriaceae (n=11,16) 8 14
Pseudomonas aeruginosa (n=11, 15) 8 13
24.Secondary Outcome
Title The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Clinically Evaluable at End of Treatment Analysis Set
Hide Description The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The clinically evaluable (CE) analysis set included all patients in the clinical modified intent-to-treat (cMITT) analysis set who met the stringent criteria for clinical evaluation described in the protocol regarding dosing, prior and concomitant medication, evaluation, etc. (pathogens in ≥5 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 291 306
Measure Type: Number
Unit of Measure: participants
All (n=39, 49) 35 42
Enterobacteriaceae (n=29, 37) 27 31
Enterobacter aerogenes (n=4, 2) 3 2
Enterobacter cloacae (n=6, 5) 6 3
Escherichia coli (n=6, 4) 5 3
Klebsiella pneumoniae (n=16, 28) 16 25
Gram- pathogens not Enterobacteriaceae (n=10,14) 8 13
Pseudomonas aeruginosa (n=10, 13) 8 12
25.Secondary Outcome
Title The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set
Hide Description The number of patients meeting the cure criteria: the patient is alive and all signs and symptoms of pneumonia have resolved or improved such that all antibacterial therapies for Nosocomial Pneumonia are stopped. No antibacterial therapy other than those outlined by the protocol has been administered for Nosocomial Pneumonia prior to end of treatment.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiologically evaluable (ME) analysis sets defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture that is susceptible to both study agents (CAZ-AVI and meropenem). (pathogens in ≥5 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 122 138
Measure Type: Number
Unit of Measure: participants
All (n=32, 40) 31 36
Enterobacteriaceae (n=28, 35) 27 31
Enterobacter aerogenes (n=4, 2) 3 2
Enterobacter cloacae (n=6, 5) 6 3
Escherichia coli (n=5, 4) 5 3
Klebsiella pneumoniae (n=16, 26) 16 25
Gram- pathogens not Enterobacteriaceae (n=4,7) 4 7
Pseudomonas aeruginosa (n=4, 6) 4 6
26.Secondary Outcome
Title The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Clinically Modified Intent-to-treat Analysis Set at Test-of-cure Visit
Hide Description The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen. (pathogens in ≥5 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 171 184
Measure Type: Number
Unit of Measure: participants
All (n=45, 54) 35 40
Enterobacteriaceae (n=34, 41) 28 29
Enterobacter aerogenes (n=4, 2) 3 2
Enterobacter cloacae (n=6, 6) 6 4
Escherichia coli (n=6, 5) 4 3
Klebsiella pneumoniae (n=20, 30) 16 22
Gram- pathogens not Enterobacteriaceae (n=11,16) 7 13
Pseudomonas aeruginosa (n=11, 15) 7 13
27.Secondary Outcome
Title The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Clinically Evaluable at Test-of-cure Analysis Set
Hide Description The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The clinically evaluable (CE) analysis set included all patients in the clinical modified intent-to-treat (cMITT) analysis set who met the stringent criteria for clinical evaluation described in the protocol regarding dosing, prior and concomitant medication, evaluation, etc. (pathogens in ≥5 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 257 270
Measure Type: Number
Unit of Measure: participants
All (n=36, 41) 29 32
Enterobacteriaceae (n=27, 30) 23 22
Enterobacter cloacae (n=5, 5) 5 3
Escherichia coli (n=5, 4) 4 3
Klebsiella pneumoniae (n=14, 22) 12 17
Gram- pathogens not Enterobacteriaceae (n=9,13) 6 12
Pseudomonas aeruginosa (n=9, 13) 6 12
28.Secondary Outcome
Title The Number of Patients With Clinical Cure in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set
Hide Description The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiologically evaluable (ME) analysis sets defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture that is susceptible to both study agents (CAZ-AVI and meropenem). (pathogens in ≥5 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 107 118
Measure Type: Number
Unit of Measure: participants
All (n=29, 32) 25 26
Enterobacteriaceae (n=26, 28) 23 22
Enterobacter cloacae (n=5, 5) 5 3
Escherichia coli (n=4, 4) 4 3
Klebsiella pneumoniae (n=14, 20) 12 17
Gram- pathogens not Enterobacteriaceae (n=3,6) 2 6
Pseudomonas aeruginosa (n=3, 6) 2 6
29.Secondary Outcome
Title Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set at End of Treatment Visit
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen. Patients infected with ceftazidime-resistant Gram negative pathogens at EOT
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 46 54
Measure Type: Number
Unit of Measure: participants
Favorable 35 39
Unfavorable 10 13
Indeterminate 1 2
30.Secondary Outcome
Title Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable at End of Treatment Analysis Set
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The extended-ME (EME) analysis set defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture regardless of susceptibility to study agents. Patients infected with ceftazidime-resistant Gram negative pathogens at EOT
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 40 49
Measure Type: Number
Unit of Measure: participants
Favorable 31 36
Unfavorable 9 13
31.Secondary Outcome
Title Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiologically evaluable (ME) analysis sets defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture that is susceptible to both study agents (CAZ-AVI and meropenem). Patients infected with ceftazidime-resistant Gram negative pathogens at EOT
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 33 40
Measure Type: Number
Unit of Measure: participants
Favorable 26 29
Unfavorable 7 11
32.Secondary Outcome
Title Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set at Test-of-cure Visit
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen. Patients infected with ceftazidime-resistant Gram negative pathogens at TOC
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 46 54
Measure Type: Number
Unit of Measure: participants
Favorable 27 27
Unfavorable 16 23
Indeterminate 3 4
33.Secondary Outcome
Title Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Extended Microbiologically Evaluable at Test-of-cure Analysis Set
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The extended-ME (EME) analysis set defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture regardless of susceptibility to study agents. Patients infected with ceftazidime-resistant Gram negative pathogens at TOC
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 37 41
Measure Type: Number
Unit of Measure: participants
Favorable 23 21
Unfavorable 14 20
34.Secondary Outcome
Title Number of Patients With a Favorable Per-patient Microbiologic Response in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set
Hide Description Per-patient "favorable" response indicates that all of the patient's baseline pathogens are "eradicated" or "presumed eradicated". Eradication is defined as: source specimen demonstrates absence of the original baseline pathogen. Presumed eradication is defined as: source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiologically evaluable (ME) analysis sets defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture that is susceptible to both study agents (CAZ-AVI and meropenem). Patients infected with ceftazidime-resistant Gram negative pathogens at TOC
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 30 32
Measure Type: Number
Unit of Measure: participants
Favorable 21 18
Unfavorable 9 14
35.Secondary Outcome
Title The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set at End of Treatment Visit
Hide Description The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen. Patients infected with ceftazidime-resistant Gram negative pathogens at EOT (pathogens in ≥5 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 46 54
Measure Type: Number
Unit of Measure: participants with favorable responses
Enterobacter aerogenes (n=4, 2) 3 2
Enterobacter cloacae (n=6, 6) 6 6
Escherichia coli (n=6, 5) 5 4
Klebsiella pneumoniae (n=20, 30) 18 26
Pseudomonas aeruginosa (n=11, 15) 8 7
36.Secondary Outcome
Title The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Extended Microbiologically Evaluable at End of Treatment Analysis Set
Hide Description The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
The extended-ME (EME) analysis set defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture regardless of susceptibility to study agents. Patients infected with ceftazidime-resistant Gram negative pathogens at EOT (pathogens in ≥5 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 40 49
Measure Type: Number
Unit of Measure: participants with favorable responses
Enterobacter aerogenes (n=4, 2) 3 2
Enterobacter cloacae (n=6, 5) 6 5
Escherichia coli (n=6, 4) 5 4
Klebsiella pneumoniae (n=16, 28) 14 25
Pseudomonas aeruginosa (n=10, 13) 8 6
37.Secondary Outcome
Title The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at End of Treatment (EOT) Visit in Microbiologically Evaluable at End of Treatment Analysis Set
Hide Description The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically evaluable (ME) analysis sets defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture that is susceptible to both study agents (CAZ-AVI and meropenem). Patients infected with ceftazidime-resistant Gram negative pathogens at EOT (pathogens in ≥5 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 33 40
Measure Type: Number
Unit of Measure: participants with favorable responses
Enterobacter aerogenes (n=4, 2) 3 2
Enterobacter cloacae (n=6, 5) 6 5
Escherichia coli (n=5, 4) 5 4
Klebsiella pneumoniae (n=16, 26) 14 23
Pseudomonas aeruginosa (n=4, 6) 3 1
38.Secondary Outcome
Title The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set at Test-of-cure Visit
Hide Description The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen. Patients infected with ceftazidime-resistant Gram negative pathogens at TOC (pathogens in ≥5 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 46 54
Measure Type: Number
Unit of Measure: participants with favorable responses
Enterobacter aerogenes (n=4, 2) 3 2
Enterobacter cloacae (n=6, 6) 5 5
Escherichia coli (n=6, 5) 4 4
Klebsiella pneumoniae (n=20, 30) 15 18
Pseudomonas aeruginosa (n=11, 15) 4 4
39.Secondary Outcome
Title The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Extended Microbiologically Evaluable at Test-of-cure Analysis Set
Hide Description The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
The extended-ME (EME) analysis set defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture regardless of susceptibility to study agents. Patients infected with ceftazidime-resistant Gram negative pathogens at TOC (pathogens in ≥5 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 37 41
Measure Type: Number
Unit of Measure: participants with favorable responses
Enterobacter cloacae (n=5, 5) 4 4
Escherichia coli (n=5, 4) 4 4
Klebsiella pneumoniae (n=14, 22) 11 14
Pseudomonas aeruginosa (n=9, 13) 3 3
40.Secondary Outcome
Title The Number of Favorable Per-pathogen Microbiologic Responses in Patients With Pathogens Resistant to Ceftazidime at Test-of-cure (TOC) Visit in Microbiologically Evaluable at Test-of-cure Analysis Set
Hide Description The number of patients with a favorable per-pathogen microbiological response: favorable microbiological response includes: Eradication where, source specimen demonstrates absence of the original baseline pathogen. Presumed eradication where, source specimen was not available to culture and the patient was assessed as a clinical cure.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically evaluable (ME) analysis sets defined as all patients in clinically evaluable (CE) analysis set with at least 1 etiologic pathogen from an adequate baseline culture that is susceptible to both study agents (CAZ-AVI and meropenem). Patients infected with ceftazidime-resistant Gram negative pathogens at TOC (pathogens in ≥5 patients)
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 30 32
Measure Type: Number
Unit of Measure: participants with favorable responses
Enterobacter cloacae (n=5, 5) 4 4
Escherichia coli (n=4, 4) 4 4
Klebsiella pneumoniae (n=14, 20) 11 13
Pseudomonas aeruginosa (n=3, 6) 1 1
41.Secondary Outcome
Title The Number of Patients With Death Due to Any Cause (All-cause Mortality) at Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set at Test-of-cure Visit
Hide Description The number of patients with death due to any cause (all-cause mortality) in microbiologically modified intent-to-treat analysis set at test-of-cure visit.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
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Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 171 184
Measure Type: Number
Unit of Measure: participants
Number of patients who died (all cause mortality) 16 14
Deaths due to disease progression 6 5
Number of patients with any AE with outcome=death 10 9
Number of patients alive 153 170
Number of patients with unknown survival status 2 0
42.Secondary Outcome
Title The Number of Patients With Death Due to Any Cause (All-cause Mortality) at Test-of-cure (TOC) Visit in Clinically Modified Intent-to-treat Analysis Set at Test-of-cure Visit
Hide Description The number of patients with death due to any cause (all-cause mortality) in clinically modified intent-to-treat analysis set at test-of-cure visit.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
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Hide Analysis Population Description
The clinical modified intent-to-treat (cMITT) included all patients who met the minimum disease criteria and received any amount of study treatment, and had either no baseline pathogens or at least one study-qualifying Gram-negative baseline pathogen.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 356 370
Measure Type: Number
Unit of Measure: participants
Number of patients who died (all cause mortality) 29 25
Deaths due to disease progression 10 6
Number of patients with any AE with outcome=death 19 19
Number of patients alive 316 341
Number of patients with unknown survival status 11 4
43.Secondary Outcome
Title The Number of Patients With Death Due to Any Cause (All-cause Mortality) at Test-of-cure (TOC) Visit in the Clinically Evaluable at Test-of-cure Analysis Set
Hide Description The number of patients with death due to any cause (all-cause mortality) in the clinically evaluable at test-of-cure analysis set.
Time Frame At the test-of-cure (TOC) visit (Day 21 to 25)
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Hide Analysis Population Description
The clinically evaluable (CE) analysis set included all patients in the clinical modified intent-to-treat (cMITT) analysis set who met the stringent criteria for clinical evaluation described in the protocol regarding dosing, prior and concomitant medication, evaluation, etc.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 257 270
Measure Type: Number
Unit of Measure: participants
Number of patients who died (all cause mortality) 11 8
Deaths due to disease progression 5 4
Number of patients with any AE with outcome=death 6 4
Number of patients alive 245 262
Number of patients with unknown survival status 1 0
44.Secondary Outcome
Title The Number of Patients With Death Due to Any Cause (All-cause Mortality) in Microbiologically Modified Intent-to-treat Analysis Set at Day 28
Hide Description The number of patients with death due to any cause (all-cause mortality) in microbiologically modified intent-to-treat analysis set at day 28.
Time Frame at Day 28 from randomization
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Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 171 184
Measure Type: Number
Unit of Measure: participants
Number of patients who died (all cause mortality) 17 16
Deaths due to disease progression 6 5
Number of patients with any AE with outcome=death 11 11
Number of patients alive 152 168
Number of patients with unknown survival status 2 0
45.Secondary Outcome
Title The Number of Patients With Death Due to Any Cause (All-cause Mortality) in Clinically Modified Intent-to-treat Analysis Set at Day 28
Hide Description The number of patients with death due to any cause (all-cause mortality) in clinically modified intent-to-treat analysis set at day 28.
Time Frame at Day 28 from randomization
Hide Outcome Measure Data
Hide Analysis Population Description
The clinical modified intent-to-treat (cMITT) included all patients who met the minimum disease criteria and received any amount of study treatment, and had either no baseline pathogens or at least one study-qualifying Gram-negative baseline pathogen.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 356 370
Measure Type: Number
Unit of Measure: participants
Number of patients who died (all cause mortality) 30 27
Deaths due to disease progression 10 6
Number of patients with any AE with outcome=death 20 21
Number of patients alive 315 339
Number of patients with unknown survival status 11 4
46.Secondary Outcome
Title The Number of Patients With Death Due to Any Cause (All-cause Mortality) in the Clinically Evaluable at Test-of-cure Analysis Set at Day 28
Hide Description The number of patients with death due to any cause (all-cause mortality) in the clinically evaluable at test-of-cure analysis set at day 28.
Time Frame at Day 28 from randomization
Hide Outcome Measure Data
Hide Analysis Population Description
The clinically evaluable (CE) analysis set included all patients in the clinical modified intent-to-treat (cMITT) analysis set who met the stringent criteria for clinical evaluation described in the protocol regarding dosing, prior and concomitant medication, evaluation, etc.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 257 270
Measure Type: Number
Unit of Measure: participants
Number of patients who died (all cause mortality) 12 9
Deaths due to disease progression 5 4
Number of patients with any AE with outcome=death 7 5
Number of patients alive 244 261
Number of patients with unknown survival status 1 0
47.Secondary Outcome
Title The Number of Patients Discharged From Hospital up to Test-of-cure (TOC) Visit in Microbiologically Modified Intent-to-treat Analysis Set
Hide Description The number of patients discharged from hospital in microbiologically modified intent-to-treat analysis set.
Time Frame up to 25 days from randomization
Hide Outcome Measure Data
Hide Analysis Population Description
The microbiological modified intent-to-treat (mMITT) analysis set included all patients who met the minimum disease criteria and received any amount of study treatment, and had at least one study-qualifying Gram-negative baseline pathogen.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 171 184
Measure Type: Number
Unit of Measure: participants
Number of patients with admission date 170 182
Number of patients with at least one discharge 71 75
1 discharge 71 74
2 discharges 0 1
>2 discharges 0 0
48.Secondary Outcome
Title The Number of Patients Discharged From Hospital up to Test-of-cure (TOC) Visit in the Clinically Modified Intent-to-treat Analysis Set
Hide Description The number of patients discharged from hospital in the clinically modified intent-to-treat analysis set.
Time Frame up to 25 days from randomization
Hide Outcome Measure Data
Hide Analysis Population Description
The clinical modified intent-to-treat (cMITT) included all patients who met the minimum disease criteria and received any amount of study treatment, and had either no baseline pathogens or at least one study-qualifying Gram-negative baseline pathogen.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 356 370
Measure Type: Number
Unit of Measure: participants
Number of patients with admission date 355 366
Number of patients with at least one discharge 206 206
1 discharge 201 200
2 discharges 5 4
>2 discharges 0 2
49.Secondary Outcome
Title The Number of Patients Discharged From Hospital up to Test-of-cure (TOC) Visit in the Clinically Evaluable at Test-of-cure Analysis Set
Hide Description The number of patients discharged from hospital in the clinically evaluable at test-of-cure analysis set.
Time Frame up to 25 days from randomization
Hide Outcome Measure Data
Hide Analysis Population Description
The clinically evaluable (CE) analysis set included all patients in the clinical modified intent-to-treat (cMITT) analysis set who met the stringent criteria for clinical evaluation described in the protocol regarding dosing, prior and concomitant medication, evaluation, etc.
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description:
2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem
meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
Overall Number of Participants Analyzed 257 270
Measure Type: Number
Unit of Measure: participants
Number of patients with admission date 256 266
Number of patients with at least one discharge 148 155
1 discharge 144 151
2 discharges 4 3
>2 discharges 0 1
Time Frame Nonserious AEs and SAEs are collected for each patient from date when informed consent is obtained until the date of final protocol follow-up, study withdrawal or date of death from any cause, whichever came first, assessed up to 28 days.
Adverse Event Reporting Description AEs spontaneously reported by the patient or care provider or reported in response to open question from the study center personnel, or revealed by observation were to be collected and recorded in the eCRF. Summary tables include all randomized patients but 62 MSRIBorig patients and 9 patients who didn't receive study treatment after randomization.
 
Arm/Group Title CAZ-AVI Meropenem
Hide Arm/Group Description 2000mg ceftazidime / 500mg avibactam intravenous (IV) infused over 2 hours plus appropriate placebo to meropenem meropenem 1000mg IV infused over 30 minutes plus CAZ-AVI placebo
All-Cause Mortality
CAZ-AVI Meropenem
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
CAZ-AVI Meropenem
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   75/405 (18.52%)      54/403 (13.40%)    
Blood and lymphatic system disorders     
Anaemia  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Cardiac disorders     
Acute coronary syndrome  1  1/405 (0.25%)  1 1/403 (0.25%)  1
Acute left ventricular failure  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Atrial fibrillation  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Cardiac arrest  1  2/405 (0.49%)  3 3/403 (0.74%)  4
Cardiac asthma  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Cardiac failure  1  4/405 (0.99%)  4 3/403 (0.74%)  3
Cardiac failure acute  1  1/405 (0.25%)  1 2/403 (0.50%)  2
Cardiac failure congestive  1  2/405 (0.49%)  2 0/403 (0.00%)  0
Cardiopulmonary failure  1  1/405 (0.25%)  1 2/403 (0.50%)  2
Cardiovascular insufficiency  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Cyanosis  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Left ventricular failure  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Ventricular fibrillation  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Endocrine disorders     
Diabetes insipidus  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Gastrointestinal disorders     
Diarrhoea  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Duodenal ulcer haemorrhage  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Gastrointestinal disorder  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Gastrointestinal haemorrhage  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Intestinal perforation  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Melaena  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Upper gastrointestinal haemorrhage  1  0/405 (0.00%)  0 1/403 (0.25%)  1
General disorders     
Death  1  3/405 (0.74%)  3 1/403 (0.25%)  1
Intentional medical device removal by patient  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Multi-organ failure  1  3/405 (0.74%)  3 1/403 (0.25%)  1
Pyrexia  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Sudden death  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Hepatobiliary disorders     
Bile duct stone  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Cholecystitis acute  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Subacute hepatic failure  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Infections and infestations     
CNS ventriculitis  1  1/405 (0.25%)  1 1/403 (0.25%)  1
Clostridium difficile colitis  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Device related sepsis  1  0/405 (0.00%)  0 2/403 (0.50%)  2
Diabetic foot infection  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Enterobacter pneumonia  1  1/405 (0.25%)  1 0/403 (0.00%)  0
HIV infection  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Infectious pleural effusion  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Influenza  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Lung infection  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Meningitis  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Osteomyelitis  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Pneumonia  1  7/405 (1.73%)  7 6/403 (1.49%)  6
Pneumonia fungal  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Postoperative wound infection  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Pulmonary sepsis  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Pulmonary tuberculosis  1  1/405 (0.25%)  1 1/403 (0.25%)  1
Sepsis  1  5/405 (1.23%)  5 4/403 (0.99%)  5
Septic shock  1  3/405 (0.74%)  3 3/403 (0.74%)  3
Tracheitis  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Tuberculosis  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Urinary tract infection  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Urosepsis  1  1/405 (0.25%)  1 1/403 (0.25%)  1
Injury, poisoning and procedural complications     
Gastrointestinal anastomotic leak  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Procedural haemorrhage  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Tracheostomy malfunction  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Weaning failure  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Investigations     
Alanine aminotransferase increased  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Aspartate aminotransferase increased  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Liver function test abnormal  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Platelet count decreased  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Metabolism and nutrition disorders     
Fluid overload  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Hyperkalaemia  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Hypoalbuminaemia  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Hyponatraemia  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Musculoskeletal and connective tissue disorders     
Myopathy  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bronchioloalveolar carcinoma  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Lung neoplasm  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Lung neoplasm malignant  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Metastases to peritoneum  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Rectal cancer metastatic  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Nervous system disorders     
Autonomic nervous system imbalance  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Brachial plexopathy  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Cerebral infarction  1  0/405 (0.00%)  0 2/403 (0.50%)  2
Cerebrospinal fluid leakage  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Haemorrhagic stroke  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Ischaemic stroke  1  1/405 (0.25%)  1 1/403 (0.25%)  1
Renal and urinary disorders     
Acute kidney injury  1  2/405 (0.49%)  2 1/403 (0.25%)  1
Renal failure  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Renal impairment  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  2/405 (0.49%)  2 0/403 (0.00%)  0
Acute respiratory failure  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Aspiration  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Atelectasis  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Bronchial secretion retention  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Bronchoplegia  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Interstitial lung disease  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Obstructive airways disorder  1  2/405 (0.49%)  2 0/403 (0.00%)  0
Pleural effusion  1  0/405 (0.00%)  0 3/403 (0.74%)  3
Pneumonia aspiration  1  4/405 (0.99%)  4 1/403 (0.25%)  1
Pneumothorax  1  1/405 (0.25%)  1 3/403 (0.74%)  3
Pulmonary embolism  1  2/405 (0.49%)  2 0/403 (0.00%)  0
Respiratory failure  1  5/405 (1.23%)  5 4/403 (0.99%)  4
Vascular disorders     
Deep vein thrombosis  1  1/405 (0.25%)  1 1/403 (0.25%)  1
Hypertensive emergency  1  0/405 (0.00%)  0 1/403 (0.25%)  1
Peripheral arterial occlusive disease  1  1/405 (0.25%)  1 0/403 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
CAZ-AVI Meropenem
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   198/405 (48.89%)      195/403 (48.39%)    
Blood and lymphatic system disorders     
Anaemia  1  24/405 (5.93%)  25 18/403 (4.47%)  21
Gastrointestinal disorders     
Abdominal pain  1  10/405 (2.47%)  11 8/403 (1.99%)  8
Constipation  1  25/405 (6.17%)  25 31/403 (7.69%)  38
Diarrhoea  1  60/405 (14.81%)  65 62/403 (15.38%)  68
Nausea  1  13/405 (3.21%)  13 7/403 (1.74%)  7
Vomiting  1  23/405 (5.68%)  28 22/403 (5.46%)  24
General disorders     
Oedema peripheral  1  17/405 (4.20%)  18 15/403 (3.72%)  15
Pyrexia  1  10/405 (2.47%)  11 13/403 (3.23%)  20
Infections and infestations     
Urinary tract infection  1  11/405 (2.72%)  11 14/403 (3.47%)  14
Investigations     
Alanine aminotransferase increased  1  16/405 (3.95%)  16 19/403 (4.71%)  20
Aspartate aminotransferase increased  1  16/405 (3.95%)  16 17/403 (4.22%)  18
Metabolism and nutrition disorders     
Hypokalaemia  1  43/405 (10.62%)  47 33/403 (8.19%)  40
Hyponatraemia  1  10/405 (2.47%)  10 6/403 (1.49%)  6
Psychiatric disorders     
Insomnia  1  4/405 (0.99%)  4 11/403 (2.73%)  11
Respiratory, thoracic and mediastinal disorders     
Pleural effusion  1  9/405 (2.22%)  10 7/403 (1.74%)  7
Skin and subcutaneous tissue disorders     
Decubitus ulcer  1  9/405 (2.22%)  13 6/403 (1.49%)  6
Rash  1  8/405 (1.98%)  8 13/403 (3.23%)  13
Vascular disorders     
Hypertension  1  14/405 (3.46%)  14 15/403 (3.72%)  16
Hypotension  1  10/405 (2.47%)  10 8/403 (1.99%)  13
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: David Wilson, Statistical Team Leader - Infection
Organization: AstraZeneca
Phone: +44 1625 517830
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01808092     History of Changes
Other Study ID Numbers: D4281C00001
First Submitted: February 28, 2013
First Posted: March 11, 2013
Results First Submitted: December 9, 2016
Results First Posted: February 3, 2017
Last Update Posted: September 6, 2017