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

Study Overview
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Brief Summary
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The purpose of this study is to compare the safety and efficacy of the antibiotic tigecycline with other antibiotics, ampicillin-sulbactam, and amoxicillin-clavulanate in the treatment of a complicated skin and/or skin structure infection (cSSSI).

Official Title
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A Multicenter, Randomized, Open-Label Comparison of the Safety And Efficacy of Tigecycline With That of Ampicillin-Sulbactam or Amoxicillin-Clavulanate to Treat Complicated Skin And Skin Structure Infections

Conditions
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Skin Diseases, Bacterial

Intervention / Treatment
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* Drug: Tigecycline
* Drug: ampicillin-sulbactam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of complicated skin or skin structure infection Male or female, 18 years or older Need for intravenous treatment for 4 to 14 days Exclusion Criteria: Skin infection that can be treated by surgery & wound care alone Diabetic foot ulcers or bedsores where the infection is present longer than 1 week Poor circulation such that amputation of the infected site is likely within a month Other exclusions apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Arm 1: Tigecycline | Drug: Tigecycline<br>* Treatment A: Tigecycline every 12 hours intravenous (IV) (an initial dose of 100 mg followed by 50 mg every 12 hours)<br>|
| Active Comparator: 2<br>Arm 2: Ampicillin-Sulbactam or Amoxicillin-Clavulanate plus or minus a glycopeptide | Drug: ampicillin-sulbactam<br>* Ampicillin-sulbactam: 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (3 g ampicillin plus 1 g sulbactam) intravenous (IV) every 6 hrs or Amoxicillin-clavulanate: 1.2 g (1000 mg amoxicillin plus 200 mg clavulanate) IV every 6 to 8 hrs. A glycopeptide antibiotic (either vancomycin 1 g IV every 12 hrs or teicoplanin IV loading dose of 400 mg the first day followed by a maintenance dose of 200 mg daily) may be added to the aminopenicillin/betalactamase inhibitor regimen if infection with methicillin-resistant staphylococcus aureus (MRSA) is suspected or confirmed within the first 72 hrs of enrollment. If culture results fail to show a resistant organism, use of the glycopeptide may be discontinued.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Clinically Evaluable (CE) Patients With Clinical Response of Cure at the Test-of-cure (TOC) Visit | 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. | up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Microbiologically Evaluable Patients With Clinical Response of Cure at the Test-of-cure (TOC) Visit | 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. | up to 6 weeks | 
| Number of Microbiologically Evaluable Patients by Microbiologic Response at Test-of-Cure (TOC) Visit | 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. | up to 6 weeks | 
| Minimum Inhibitory Concentration (MIC) 50 and 90 by Baseline Isolate | 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. | up to 6 weeks | 
| Inpatient Healthcare Resource Utilization on or Before Test-of-Cure - Number of Patients | 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. | up to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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skin infection, antibiotics