A multicenter trial of the efficacy and safety of tigecycline versus imipenem/cilastatin in patients with complicated intra-abdominal infections [Study ID Numbers: 3074A1-301-WW; ClinicalTrials.gov Identifier: NCT00081744]

BMC Infect Dis. 2005 Oct 19:5:88. doi: 10.1186/1471-2334-5-88.

Abstract

Background: Complicated intra-abdominal infections (cIAI) remain challenging to treat because of their polymicrobial etiology including multi-drug resistant bacteria. The efficacy and safety of tigecycline, an expanded broad-spectrum glycylcycline antibiotic, was compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI.

Methods: A prospective, double-blind, multinational trial was conducted in which patients with cIAI randomly received intravenous (IV) tigecycline (100 mg initial dose, then 50 mg every 12 hours [q12h]) or IV IMI/CIS (500/500 mg q6h or adjusted for renal dysfunction) for 5 to14 days. Clinical response at the test-of-cure (TOC) visit (14-35 days after therapy) for microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations were the co-primary efficacy endpoint populations.

Results: A total of 825 patients received >or= 1 dose of study drug. The primary diagnoses for the ME group were complicated appendicitis (59%), and intestinal (8.8%) and gastric/duodenal perforations (4.6%). For the ME group, clinical cure rates at TOC were 80.6% (199/247) for tigecycline versus 82.4% (210/255) for IMI/CIS (95% CI -8.4, 5.1 for non-inferiority tigecycline versus IMI/CIS). Corresponding clinical cure rates within the m-mITT population were 73.5% (227/309) for tigecycline versus 78.2% (244/312) for IMI/CIS (95% CI -11.0, 2.5). Nausea (31.0% tigecycline, 24.8% IMI/CIS [P = 0.052]), vomiting (25.7% tigecycline, 19.4% IMI/CIS [P = 0.037]), and diarrhea (21.3% tigecycline, 18.9% IMI/CIS [P = 0.435]) were the most frequently reported adverse events.

Conclusion: This study demonstrates that tigecycline is as efficacious as imipenem/cilastatin in the treatment of patients with cIAI.

Trial registration: ClinicalTrials.gov NCT00081744.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdomen / microbiology*
  • Adult
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / pharmacology*
  • Appendicitis / complications
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / etiology
  • Cholecystitis / complications
  • Cholecystitis / drug therapy
  • Cilastatin / adverse effects
  • Cilastatin / pharmacology
  • Cilastatin, Imipenem Drug Combination
  • Diverticulitis / complications
  • Diverticulitis / drug therapy
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Imipenem / adverse effects
  • Imipenem / pharmacology
  • Intestinal Perforation / complications
  • Male
  • Middle Aged
  • Minocycline / adverse effects
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacology
  • Peptic Ulcer Perforation / complications
  • Peritonitis / complications
  • Peritonitis / drug therapy
  • Tigecycline

Substances

  • Anti-Bacterial Agents
  • Drug Combinations
  • Cilastatin
  • Tigecycline
  • Imipenem
  • Cilastatin, Imipenem Drug Combination
  • Minocycline

Associated data

  • ClinicalTrials.gov/NCT00081744