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

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

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).

Study Overview

• Status: Completed
• Conditions: Skin Diseases, Bacterial
• Intervention / Treatment: Drug: Tigecycline; Drug: ampicillin-sulbactam

• Study Type: Interventional
• Enrollment (Actual): 550
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
    • Montreal, Quebec, Canada, H1T 2M4
    • Sherbrooke, Quebec, Canada, J1H 5N4
    • Trois-Rivieres, Quebec, Canada, G8Z 3R9
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
• Hong Kong
  • Hong Kong, Hong Kong
• Israel
  • Ramat Gan, Israel, 52621
• Korea, Republic of
  • Daejeon, Korea, Republic of, 301-721
  • Incheon, Korea, Republic of, 405-760
  • Seoul, Korea, Republic of, 120-752
  • Seoul, Korea, Republic of, 133-791
• Lebanon
  • Beirut, Lebanon, 110 32090
• Malaysia
  • Pulau Pinang, Malaysia, 10990
• Philippines
  • Manila, Philippines, 1000
  • Manila, Philippines, 1014
• Singapore
  • Singapore, Singapore, 169608
• South Africa
  • Cape Town, South Africa, 7531
  • Gauteng, South Africa, 0181
  • KZ-Natal, South Africa, 3610
  • Mpumalanga, South Africa, 1050
• Taiwan
  • Taipei, Taiwan, 220
• Thailand
  • Bangkok, Thailand, 10400
  • Bangkok, Thailand, 10700
  • Bangkok, Thailand, 10330
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
  • California
    • Chula Vista, California, United States, 91911
    • Mission Viejo, California, United States, 92691
    • National City, California, United States, 91950
  • Colorado
    • Denver, Colorado, United States, 80218
  • District of Columbia
    • Washington, District of Columbia, United States, 20017
    • Washington, District of Columbia, United States, 20037
  • Florida
    • Orlando, Florida, United States, 32803
    • Vero Beach, Florida, United States, 32960
  • Georgia
    • Ft. Gordon, Georgia, United States, 30905
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
  • Illinois
    • Decatur, Illinois, United States, 62526
    • Naperville, Illinois, United States, 60540
    • Springfield, Illinois, United States, 62702
  • Kansas
    • Topeka, Kansas, United States, 66606
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02139
    • Worcester, Massachusetts, United States, 01655
  • Michigan
    • Detroit, Michigan, United States, 48202
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
    • Neptune, New Jersey, United States, 07754
  • New York
    • Buffalo, New York, United States, 14215
    • Elmira, New York, United States, 14905
    • New Hyde Park, New York, United States, 11040
  • Ohio
    • Columbus, Ohio, United States, 43214
    • Lima, Ohio, United States, 45801
  • Pennsylvania
    • Lansdale, Pennsylvania, United States, 19446
    • Philadelphia, Pennsylvania, United States, 19140
  • Texas
    • Fort Worth, Texas, United States, 76104
    • Ft. Worth, Texas, United States, 76104
    • Houston, Texas, United States, 77026

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Arm 1: Tigecycline	Drug: Tigecycline; Treatment A: Tigecycline every 12 hours intravenous (IV) (an initial dose of 100 mg followed by 50 mg every 12 hours)
Active Comparator: 2; Arm 2: Ampicillin-Sulbactam or Amoxicillin-Clavulanate plus or minus a glycopeptide	Drug: ampicillin-sulbactam; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Investigators: Principal Investigator: Trial Manager, For Hong Kong: medinfo@wyeth.com; Principal Investigator: Trial Manager, For Taiwan: medinfo@wyeth.com; Principal Investigator: Trial Manager, For South Africa: ZAFinfo@wyeth.com

Publications and helpful links

General Publications

• Matthews P, Alpert M, Rahav G, Rill D, Zito E, Gardiner D, Pedersen R, Babinchak T, McGovern PC; Tigecycline 900 cSSSI Study Group. A randomized trial of tigecycline versus ampicillin-sulbactam or amoxicillin-clavulanate for the treatment of complicated skin and skin structure infections. BMC Infect Dis. 2012 Nov 12;12:297. doi: 10.1186/1471-2334-12-297.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: August 21, 2006
• First Submitted That Met QC Criteria: August 23, 2006
• First Posted (Estimate): August 24, 2006

Study Record Updates

• Last Update Posted (Estimate): August 9, 2012
• Last Update Submitted That Met QC Criteria: August 8, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: antibiotics; skin infection
• Additional Relevant MeSH Terms: Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Infections; Skin Diseases; Skin Diseases, Bacterial; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; beta-Lactamase Inhibitors; Ampicillin; Tigecycline; Sulbactam; Sultamicillin
• Other Study ID Numbers: 3074A1-900