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Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Participants With Complicated Urinary Tract Infections (IGNITE3)

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ClinicalTrials.gov Identifier: NCT03032510
Recruitment Status : Completed
First Posted : January 26, 2017
Results First Posted : October 2, 2019
Last Update Posted : October 2, 2019
Sponsor:
Information provided by (Responsible Party):
Tetraphase Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Complicated Urinary Tract Infections
Interventions Drug: Eravacycline
Drug: Ertapenem
Drug: Placebo
Drug: Levofloxacin
Enrollment 1205
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Eravacycline (Intravenous)/Levofloxacin (Oral) Ertapenem (Intravenous)/Levofloxacin (Oral)
Hide Arm/Group Description

Eravacycline 1.5mg/kg IV q24h

Placebo IV q24h

Levofloxacin (PO)

Ertapenem 1g IV q24h

Placebo IV q24h

Levofloxacin (PO)

Period Title: Overall Study
Started 603 602
Completed 576 584
Not Completed 27 18
Reason Not Completed
Adverse Event             5             2
Lost to Follow-up             8             7
Withdrawal by Subject             8             7
Subject noncompliance             4             2
Physician Decision             2             0
Arm/Group Title Eravacycline (Intravenous)/Levofloxacin (Oral) Ertapenem (Intravenous)/Levofloxacin (Oral) Total
Hide Arm/Group Description

Eravacycline 1.5 mg/kg IV q24h

Placebo IV

Levofloxacin PO

Ertapenem 1.0g IV q24h

Placebo IV

Levofloxacin PO

Total of all reporting groups
Overall Number of Baseline Participants 603 602 1205
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 603 participants 602 participants 1205 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
338
  56.1%
331
  55.0%
669
  55.5%
>=65 years
265
  43.9%
271
  45.0%
536
  44.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 603 participants 602 participants 1205 participants
57.1  (18.16) 56.5  (19.34) 56.8  (18.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 603 participants 602 participants 1205 participants
Female
330
  54.7%
343
  57.0%
673
  55.9%
Male
273
  45.3%
259
  43.0%
532
  44.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 603 participants 602 participants 1205 participants
Hispanic or Latino
11
   1.8%
15
   2.5%
26
   2.2%
Not Hispanic or Latino
592
  98.2%
587
  97.5%
1179
  97.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 603 participants 602 participants 1205 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   0.2%
0
   0.0%
1
   0.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   0.3%
1
   0.2%
3
   0.2%
White
600
  99.5%
601
  99.8%
1201
  99.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 603 participants 602 participants 1205 participants
Latvia 36 39 75
Austria 0 1 1
Romania 54 59 113
Hungary 56 66 122
United States 9 13 22
Ukraine 148 137 285
Georgia 33 40 73
Slovakia 18 13 31
Bulgaria 61 42 103
Estonia 21 20 41
Russia 126 143 269
Poland 23 17 40
Moldova 18 12 30
1.Primary Outcome
Title Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the EOI Visit
Hide Description This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to <10^4 colony-forming units/milliliter (CFU/mL). An outcome of Responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.
Time Frame End of Infusion
Hide Outcome Measure Data
Hide Analysis Population Description
micro-ITT included all participants in the ITT population who had at least 1 baseline bacterial pathogen from a urine or blood culture that caused a urinary tract infection (UTI) against which eravacycline and ertapenem had expected antibacterial activity.
Arm/Group Title Eravacycline (Intravenous) Ertapenem (Intravenous)
Hide Arm/Group Description:
Eravacycline was administered IV at a dose of 1.5 mg/kg of body weight q24h. At minimum, the first 5 doses were administered IV. An IV-to-PO transition could occur after dose 5. During PO administration, subjects received 750 mg of levofloxacin once daily. Total treatment duration was 7 or 10 days.
Ertapenem was administered IV at a dose of 1 g q24h. At minimum, the first 5 doses were administered IV. An IV-to-PO transition could occur after dose 5. During PO administration, subjects received 750 mg of levofloxacin once daily. Total treatment duration was 7 or 10 days.
Overall Number of Participants Analyzed 428 403
Measure Type: Count of Participants
Unit of Measure: Participants
Responder
363
  84.8%
382
  94.8%
Non-responder
51
  11.9%
7
   1.7%
Indeterminate
14
   3.3%
14
   3.5%
2.Primary Outcome
Title Proportion of Participants in the Micro-ITT Population Demonstrating Clinical Cure and Microbiologic Success at the Test-Of-Cure (TOC) Visit
Hide Description This was the co-primary outcome measure for the Food and Drug Administration (FDA). The primary objective was to demonstrate the non-inferiority (NI) of eravacycline to ertapenem in responder outcome, which was derived from both clinical and microbiological responses, in the micro-ITT population. Clinical responses were either cure, failure, or indeterminate/missing; microbiological responses were characterized programmatically as either success, failure, or indeterminate/missing. Clinical cure was defined as complete resolution or significant improvement of signs or symptoms of the infection; microbiological success was a reduction of the baseline pathogen(s) to <10^4 colony-forming units/milliliter (CFU/mL). An outcome of responder required a clinical response of cure and a microbiological response of success. Any other combination of the clinical and microbiological responses was considered either Non-responder or Indeterminate.
Time Frame TOC visit (14-17 days after randomization)
Hide Outcome Measure Data
Hide Analysis Population Description
micro-ITT included all participants in the ITT population who had at least 1 baseline bacterial pathogen from a urine or blood culture that caused a urinary tract infection (UTI) against which eravacycline and ertapenem had expected antibacterial activity.
Arm/Group Title Eravacycline Ertapenem
Hide Arm/Group Description:
micro-ITT included all participants in the ITT population who had at least 1 baseline bacterial pathogen from a urine or blood culture that caused a urinary tract infection (UTI) against which eravacycline and ertapenem had expected antibacterial activity.
micro-ITT included all participants in the ITT population who had at least 1 baseline bacterial pathogen from a urine or blood culture that caused a urinary tract infection (UTI) against which eravacycline and ertapenem had expected antibacterial activity.
Overall Number of Participants Analyzed 428 403
Measure Type: Count of Participants
Unit of Measure: Participants
Responder
293
  68.5%
302
  74.9%
Non-responder
116
  27.1%
86
  21.3%
Indeterminate
19
   4.4%
15
   3.7%
3.Secondary Outcome
Title Proportion of Participants in the ITT Population With Favorable Clinical Outcomes at TOC Visit
Hide Description

Clinical cure: A complete resolution or significant improvement of signs or symptoms of the infection such that no rescue/non-study antibacterial medication was required to treat the cUTI that presented at study entry.

Clinical failure: Subjects were classified as clinical failure in the event of

  • Death related to cUTI at any timepoint
  • Persistence of clinical symptoms of cUTI or new symptoms developed
  • Initiation of rescue/non-study antibacterial medication for cUTI Indeterminate: Study data were listed as indeterminate if the outcome was other than clinical cure or clinical failure. The reason for an indeterminate designation had to be provided Missing: Study data were listed as missing if the Investigator did not complete an assessment or if the subject did not complete the study visit.
Time Frame TOC visit (14-17 days after randomization)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT included all randomized participants, regardless of receiving study drug or not.
Arm/Group Title Eravacycline (Intravenous)/Levofloxacin (Oral) Ertapenem (Intravenous)/Levofloxacin (Oral)
Hide Arm/Group Description:
ITT included all randomized participants, regardless of receiving study drug or not.
ITT included all randomized participants, regardless of receiving study drug or not.
Overall Number of Participants Analyzed 603 602
Measure Type: Count of Participants
Unit of Measure: Participants
Clinical Cure
547
  90.7%
566
  94.0%
Clinical Failure
31
   5.1%
20
   3.3%
Indeterminate/missing
25
   4.1%
16
   2.7%
Time Frame The time frame for adverse event reporting was from the first dose of study drug through 30 days after the last dose of study drug or the FU visit (whichever was later).
Adverse Event Reporting Description The safety population was all randomized subjects who receive any amount of study drug. All safety analyses were conducted in this population and are presented by treatment actually received (not as randomized). One subject randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.
 
Arm/Group Title Eravacycline (Intravenous) Ertapenem (Intravenous)
Hide Arm/Group Description Eravacycline 1.5 mg/kg IV -The safety population was all randomized subjects who receive any amount of study drug. All safety analyses were conducted in this population and are presented by treatment actually received (not as randomized). One subject randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis. Ertapenem 1 g IV-The safety population was all randomized subjects who receive any amount of study drug. All safety analyses were conducted in this population and are presented by treatment actually received (not as randomized). One subject randomized to the ertapenem group received a dose of eravacycline and was included in the eravacycline group in the safety analysis.
All-Cause Mortality
Eravacycline (Intravenous) Ertapenem (Intravenous)
Affected / at Risk (%) Affected / at Risk (%)
Total   3/601 (0.50%)   2/600 (0.33%) 
Hide Serious Adverse Events
Eravacycline (Intravenous) Ertapenem (Intravenous)
Affected / at Risk (%) Affected / at Risk (%)
Total   11/601 (1.83%)   6/600 (1.00%) 
Cardiac disorders     
Acute myocardial infarction  1  1/601 (0.17%)  0/600 (0.00%) 
Cardiorenal syndrome  1  0/601 (0.00%)  1/600 (0.17%) 
Myocardial infarction  1  1/601 (0.17%)  0/600 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  1/601 (0.17%)  0/600 (0.00%) 
Haemorrhoids  1  0/601 (0.00%)  1/600 (0.17%) 
Ileus  1  1/601 (0.17%)  0/600 (0.00%) 
Immune system disorders     
Drug hypersensitivity  1  1/601 (0.17%)  0/600 (0.00%) 
Infections and infestations     
Clostridium difficile colitis  1  0/601 (0.00%)  1/600 (0.17%) 
Pneumonia  1  1/601 (0.17%)  0/600 (0.00%) 
Renal abscess  1  0/601 (0.00%)  1/600 (0.17%) 
Urosepsis  1  1/601 (0.17%)  0/600 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Meningioma  1  0/601 (0.00%)  1/600 (0.17%) 
Nervous system disorders     
Cerebrovascular accident  1  2/601 (0.33%)  0/600 (0.00%) 
Renal and urinary disorders     
Renal colic  1  1/601 (0.17%)  0/600 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  1/601 (0.17%)  0/600 (0.00%) 
Skin and subcutaneous tissue disorders     
Decubitus ulcer  1  1/601 (0.17%)  0/600 (0.00%) 
Vascular disorders     
Aneurysm ruptured  1  2/601 (0.33%)  1/600 (0.17%) 
Circulatory collapse  1  0/601 (0.00%)  1/600 (0.17%) 
Deep vein thrombosis  1  1/601 (0.17%)  0/600 (0.00%) 
1
Term from vocabulary, MedDra Version 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Eravacycline (Intravenous) Ertapenem (Intravenous)
Affected / at Risk (%) Affected / at Risk (%)
Total   174/601 (28.95%)   52/600 (8.67%) 
Gastrointestinal disorders     
Nausea  1  84/601 (13.98%)  10/600 (1.67%) 
Vomiting  1  31/601 (5.16%)  4/600 (0.67%) 
Diarrhoea  1  18/601 (3.00%)  17/600 (2.83%) 
General disorders     
Infusion site phlebitis  1  24/601 (3.99%)  3/600 (0.50%) 
Headache  1  17/601 (2.83%)  18/600 (3.00%) 
1
Term from vocabulary, MedDra Version 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Tetraphase
Phone: 617-715-3600
EMail: medinfo@tphase.com
Layout table for additonal information
Responsible Party: Tetraphase Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03032510    
Other Study ID Numbers: TP-434-021
First Submitted: January 17, 2017
First Posted: January 26, 2017
Results First Submitted: July 12, 2019
Results First Posted: October 2, 2019
Last Update Posted: October 2, 2019