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Study Comparing the Safety and Efficacy of Tigecycline With Ampicillin-Sulbactam or Amoxicillin-Clavulanate to Treat Skin Infections

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00368537
Recruitment Status : Completed
First Posted : August 24, 2006
Results First Posted : August 9, 2012
Last Update Posted : August 9, 2012
Sponsor:
Information provided by (Responsible Party):
Wyeth is now a wholly owned subsidiary of Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Skin Diseases, Bacterial
Interventions Drug: Tigecycline
Drug: ampicillin-sulbactam
Enrollment 550
Recruitment Details Patients were recruited worldwide from September 2006 to August 2008.
Pre-assignment Details Patients were screened according to the inclusion/exclusion criteria. Once informed consent was obtained, the patient was enrolled into the study and assigned a randomization number and a treatment regimen.
Arm/Group Title Tigecycline Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Hide Arm/Group Description Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours) Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
Period Title: Randomization
Started 281 269
Completed 268 263
Not Completed 13 6
Reason Not Completed
No study drug dosed             13             6
Period Title: Baseline Participants
Started 268 263
Completed 244 239
Not Completed 24 24
Reason Not Completed
Lost to Follow-up             16             17
Withdrawal by Subject             6             4
Death             1             2
No susceptibility             1             0
Patient uncompliant             0             1
Arm/Group Title Tigecycline Ampicillin-Sulbactam or Amoxicillin-Clavulanate Total
Hide Arm/Group Description Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours) Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours. Total of all reporting groups
Overall Number of Baseline Participants 268 263 531
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 268 participants 263 participants 531 participants
51.10  (16.11) 51.54  (16.90) 51.32  (16.49)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 268 participants 263 participants 531 participants
Female
105
  39.2%
94
  35.7%
199
  37.5%
Male
163
  60.8%
169
  64.3%
332
  62.5%
1.Primary Outcome
Title Number of Clinically Evaluable (CE) Patients With Clinical Response of Cure at the Test-of-cure (TOC) Visit
Hide Description Investigator assigned clinical response of cure of the cSSSI defined as: resolution of all clinical signs and symptoms of infection (healing of chronic underlying skin ulcer not required) or improvement of signs or symptoms of the infection to such an extent that no further antibacterial therapy was necessary. CE population were those who completed TOC assessment of cure or failure (but not indeterminate) or, in case of premature discontinuation due to lack of efficacy, had completed end of treatment assessment such that assessment of clinical response could be made.
Time Frame up to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Clinically Evaluable (CE): Patients with cSSSI, no Pseudomonas aeruginosa as sole baseline isolate, met major inclusion/exclusion criteria, ≤24 hrs antibiotics pre-baseline, had ≥4 days of study drug, compliant with therapy. Excludes indeterminates.
Arm/Group Title Tigecycline Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Hide Arm/Group Description:
Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)
Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
Overall Number of Participants Analyzed 209 196
Measure Type: Number
Unit of Measure: participants
162 152
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tigecycline, Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 2-sided 95% CI (corrected for continuity) was calculated for the true difference between the cure rates. Non-inferiority will be concluded if the lower limit of the 2-sided CI is greater than -15%.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.0
Confidence Interval 95%
-8.7 to 8.6
Estimation Comments Confidence interval calculated using asymptotic method corrected for continuity. Difference= Tigecycline minus Ampicillin-Sulbactam or Amoxicillin-Clavulanate.
2.Secondary Outcome
Title Number of Microbiologically Evaluable Patients With Clinical Response of Cure at the Test-of-cure (TOC) Visit
Hide Description Investigator assigned clinical response of cure of the cSSSI defined as: resolution of all clinical signs and symptoms of infection (healing of chronic underlying skin ulcer not required) or improvement of signs or symptoms of the infection to such an extent that no further antibacterial therapy was necessary. ME population were subjects who were CE and had baseline culture with at least 1 identified isolate that was susceptible to study drug and comparator. TOC performed 8-50 days after last dose of study drug.
Time Frame up to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically Evaluable patients:Clinically Evaluable (CE) patients who had baseline culture with ≥1 identified pathogen susceptible to both study drugs (ie, the pathogen is susceptible to tigecycline and comparator). Excludes indeterminates.
Arm/Group Title Tigecycline Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Hide Arm/Group Description:
Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)
Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
Overall Number of Participants Analyzed 120 99
Measure Type: Number
Unit of Measure: participants
96 77
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tigecycline, Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 2-sided 95% CI (corrected for continuity) was calculated for the true difference between the cure rates. Non-inferiority will be concluded if the lower limit of the 2-sided CI is greater than -15%.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.2
Confidence Interval 95%
-9.6 to 14.0
Estimation Comments Confidence interval calculated using asymptotic method corrected for continuity. Difference= Tigecycline minus Ampicillin-Sulbactam or Amoxicillin-Clavulanate.
3.Secondary Outcome
Title Number of Microbiologically Evaluable Patients by Microbiologic Response at Test-of-Cure (TOC) Visit
Hide Description Microbiological response assessed at patient level. Eradication=baseline isolate not present in repeat culture from the original infection site; Presumed Eradication=clinical response of cure precluded the availability of a specimen for culture; Persistence=baseline isolate present in repeat culture from the original infection site; Presumed Persistence=culture data not available for patients with a clinical response of failure; Superinfection=culture from the primary infection site had new pathogen not identified as a baseline isolate and clinical response was failure.
Time Frame up to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Microbiologically Evaluable patients:CE patients who had baseline culture with ≥1 identified pathogen susceptible to both study drugs (ie, the pathogen is susceptible to tigecycline and comparator). TOC performed 8-50 days after last dose of study drug.
Arm/Group Title Tigecycline Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Hide Arm/Group Description:
Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)
Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
Overall Number of Participants Analyzed 120 99
Measure Type: Number
Unit of Measure: participants
Eradication + presumed eradication 95 76
Persistence + Presumed persistence 25 23
Superinfection 2 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tigecycline, Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Comments Group comparison of eradication + presumed eradication
Type of Statistical Test Non-Inferiority or Equivalence
Comments A 2-sided 95% CI (corrected for continuity) was calculated for the true difference between the cure rates. Non-inferiority will be concluded if the lower limit of the 2-sided CI is greater than -15%.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.4
Confidence Interval 95%
-9.6 to 14.4
Estimation Comments Confidence interval calculated using asymptotic method corrected for continuity. Difference= Tigecycline minus Ampicillin-Sulbactam or Amoxicillin-Clavulanate.
4.Secondary Outcome
Title Minimum Inhibitory Concentration (MIC) 50 and 90 by Baseline Isolate
Hide Description In vitro activity of the study drugs against a range of pathogenic bacteria that cause complicated skin and skin structure infection (cSSSI) were analyzed using MIC. MIC 50 and MIC 90 are the lowest concentrations of a drug that inhibit the growth of 50% and 90% of a microorganism, respectively. TOC performed 8-50 days after last dose of study drug.
Time Frame up to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
m-mITT: Patients with ≥1 dose of study drug, had cSSSI and baseline isolate from infection site / blood. MIC reported for isolates present in ≥10 m-mITT patients. In the categories below "n" is the actual number of isolates used to caluculate the MIC 50 and MIC 90.
Arm/Group Title Tigecycline Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Hide Arm/Group Description:
Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)
Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
Overall Number of Participants Analyzed 120 99
Measure Type: Number
Unit of Measure: mcg/mL
Enterococcus Faecalis MIC50 (n=20,20) 0.12 1.00
Enterococcus Faecalis MIC90 (n=20,20) 0.25 1.00
Escherichia Coli MIC50 (n=29,29) 0.25 8.00
Escherichia Coli MIC90 (n=29,29) 0.50 32.00
Klebsiella Pneumoniae MIC50 (n=13,13) 0.50 2.00
Klebsiella Pneumoniae MIC90 (n=13,13) 2.00 8.00
Staphylococcus Aureus MIC50 (n=176,176) 0.12 2.00
Staphylococcus Aureus MIC90 (n=176,176) 0.25 8.00
Streptococcus Agalactiae MIC50 (n=18,18) 0.03 0.12
Streptococcus Agalactiae MIC90 (n=18,18) 0.06 0.12
Streptococcus Pyogenes MIC50 (n=18,18) 0.03 0.06
Streptococcus Pyogenes MIC90 (n=18,18) 0.06 0.06
5.Secondary Outcome
Title Inpatient Healthcare Resource Utilization on or Before Test-of-Cure - Number of Patients
Hide Description Healthcare resource utilization assessment included intensive care unit (ICU) and non-ICU inpatient hospitalization. TOC performed 8-50 days after last dose of study drug.
Time Frame up to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All patients who received at least 1 dose of study article.
Arm/Group Title Tigecycline Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Hide Arm/Group Description:
Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours)
Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
Overall Number of Participants Analyzed 268 263
Measure Type: Number
Unit of Measure: participants
Intensive care unit 6 9
Non-ICU inpatient hospitalization 268 263
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tigecycline, Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Comments Intensive care unit
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.444
Comments [Not Specified]
Method Fisher Exact
Comments 2-sided
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.2
Confidence Interval 95%
-4.4 to 2.0
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description This data represents the number of times a given adverse event was reported. The given participant may have experienced more than one adverse event. We are looking at the frequency of adverse events based on event and not by participant.
 
Arm/Group Title Tigecycline Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Hide Arm/Group Description Tigecycline every 12 hours IV (an initial dose of 100 mg followed by 50 mg every 12 hours) Ampicillin-sulbactam 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) IV every 6 hours or amoxicillin-clavulanate 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hours.
All-Cause Mortality
Tigecycline Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Tigecycline Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Affected / at Risk (%) Affected / at Risk (%)
Total   38/268 (14.18%)   29/263 (11.03%) 
Blood and lymphatic system disorders     
International normalized ratio increased *  0/268 (0.00%)  1/263 (0.38%) 
Cardiac disorders     
Heart arrest *  3/268 (1.12%)  2/263 (0.76%) 
Myocardial infarct *  1/268 (0.37%)  0/263 (0.00%) 
Ventricular tachycardia *  1/268 (0.37%)  0/263 (0.00%) 
Gastrointestinal disorders     
Cholecystitis *  1/268 (0.37%)  0/263 (0.00%) 
Diarrhea *  1/268 (0.37%)  0/263 (0.00%) 
Esophageal hemorrhage *  0/268 (0.00%)  1/263 (0.38%) 
Gastrointestinal hemorrhage *  1/268 (0.37%)  0/263 (0.00%) 
Hepatic failure *  0/268 (0.00%)  1/263 (0.38%) 
Liver function tests abnormal *  0/268 (0.00%)  1/263 (0.38%) 
Nausea *  1/268 (0.37%)  0/263 (0.00%) 
Peptic ulcer *  1/268 (0.37%)  0/263 (0.00%) 
Stomach ulcer *  0/268 (0.00%)  1/263 (0.38%) 
Vomiting *  1/268 (0.37%)  0/263 (0.00%) 
General disorders     
Cellulitis *  7/268 (2.61%)  6/263 (2.28%) 
Infection *  6/268 (2.24%)  1/263 (0.38%) 
Abscess *  1/268 (0.37%)  2/263 (0.76%) 
Chest pain *  2/268 (0.75%)  0/263 (0.00%) 
General physical health deterioration *  1/268 (0.37%)  1/263 (0.38%) 
Asthenia *  1/268 (0.37%)  0/263 (0.00%) 
Carcinoma *  0/268 (0.00%)  1/263 (0.38%) 
Fever *  0/268 (0.00%)  1/263 (0.38%) 
Generalized edema *  0/268 (0.00%)  1/263 (0.38%) 
Overdose *  1/268 (0.37%)  0/263 (0.00%) 
Retroperitoneal hemorrhage *  1/268 (0.37%)  0/263 (0.00%) 
Sepsis *  1/268 (0.37%)  0/263 (0.00%) 
Septic shock *  1/268 (0.37%)  0/263 (0.00%) 
Traumatic hematoma *  1/268 (0.37%)  0/263 (0.00%) 
Metabolism and nutrition disorders     
Dehydration *  1/268 (0.37%)  1/263 (0.38%) 
Hypoglycemia *  1/268 (0.37%)  1/263 (0.38%) 
Healing abnormal *  0/268 (0.00%)  1/263 (0.38%) 
Musculoskeletal and connective tissue disorders     
Necrotising fasciitis *  0/268 (0.00%)  2/263 (0.76%) 
Osteomyelitis *  0/268 (0.00%)  1/263 (0.38%) 
Nervous system disorders     
Convulsion *  1/268 (0.37%)  0/263 (0.00%) 
Encephalopathy *  0/268 (0.00%)  1/263 (0.38%) 
Renal and urinary disorders     
Acute kidney failure *  3/268 (1.12%)  1/263 (0.38%) 
Kidney failure *  0/268 (0.00%)  1/263 (0.38%) 
Kidney function abnormal *  1/268 (0.37%)  0/263 (0.00%) 
Urinary tract infection *  0/268 (0.00%)  1/263 (0.38%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia *  3/268 (1.12%)  0/263 (0.00%) 
Lung edema *  1/268 (0.37%)  1/263 (0.38%) 
Respiratory failure *  1/268 (0.37%)  1/263 (0.38%) 
Carcinoma of lung *  1/268 (0.37%)  0/263 (0.00%) 
Chronic obstructive airways disease *  0/268 (0.00%)  1/263 (0.38%) 
Skin and subcutaneous tissue disorders     
Skin necrosis *  2/268 (0.75%)  1/263 (0.38%) 
Herpes simplex *  1/268 (0.37%)  0/263 (0.00%) 
Vascular disorders     
Pulmonary embolus *  1/268 (0.37%)  1/263 (0.38%) 
Deep vein thrombosis *  1/268 (0.37%)  0/263 (0.00%) 
Occlusion *  1/268 (0.37%)  0/263 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Tigecycline Ampicillin-Sulbactam or Amoxicillin-Clavulanate
Affected / at Risk (%) Affected / at Risk (%)
Total   396/268 (147.76%)   241/263 (91.63%) 
Blood and lymphatic system disorders     
Anemia *  8/268 (2.99%)  7/263 (2.66%) 
Gastrointestinal disorders     
Nausea *  117/268 (43.66%)  44/263 (16.73%) 
Vomiting *  64/268 (23.88%)  14/263 (5.32%) 
Diarrhea *  38/268 (14.18%)  14/263 (5.32%) 
Constipation *  17/268 (6.34%)  22/263 (8.37%) 
Dyspepsia *  17/268 (6.34%)  7/263 (2.66%) 
General disorders     
Headache *  20/268 (7.46%)  22/263 (8.37%) 
Pain *  15/268 (5.60%)  18/263 (6.84%) 
Abdominal pain *  17/268 (6.34%)  7/263 (2.66%) 
Fever *  9/268 (3.36%)  6/263 (2.28%) 
Chest pain *  5/268 (1.87%)  8/263 (3.04%) 
Metabolism and nutrition disorders     
Hypokalemia *  6/268 (2.24%)  17/263 (6.46%) 
Nervous system disorders     
Insomnia *  22/268 (8.21%)  17/263 (6.46%) 
Anxiety *  9/268 (3.36%)  7/263 (2.66%) 
Dizziness *  9/268 (3.36%)  6/263 (2.28%) 
Skin and subcutaneous tissue disorders     
Pruritus *  15/268 (5.60%)  16/263 (6.08%) 
Vascular disorders     
Hypertension *  8/268 (2.99%)  9/263 (3.42%) 
*
Indicates events were collected by non-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.
The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
Results Point of Contact
Name/Title: U. S. Contact Center
Organization: Wyeth
Responsible Party: Wyeth is now a wholly owned subsidiary of Pfizer
ClinicalTrials.gov Identifier: NCT00368537     History of Changes
Other Study ID Numbers: 3074A1-900
First Submitted: August 21, 2006
First Posted: August 24, 2006
Results First Submitted: September 30, 2009
Results First Posted: August 9, 2012
Last Update Posted: August 9, 2012