BACKGROUND: Empiric treatment of complicated intra-abdominal infections (cIAI) represents a clinical challenge because of the diverse bacteriology and the emergence of bacterial resistance. The efficacy and safety of tigecycline (TGC), a first-in-class, expanded broad-spectrum glycylcycline antibiotic, were compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI. METHODS: In this prospective, double-blind, phase 3, multinational trial, patients were randomly assigned to intravenous (i.v.) TGC (100 mg initial dose, then 50 mg every 12 h) or i.v. IMI/CIS (500/500 mg every 6 h) for 5-14 days. Clinical response was assessed at the test-of-cure (TOC) visit (14-35 days after therapy) for microbiologically evaluable (ME) and microbiologically modified intent-to-treat (m-mITT) populations (co-primary efficacy endpoint populations in which cure/failure response rates were determined). RESULTS:Of 817 mITT patients (i.e., received > or = 1 dose of study drug), 641 (78%) comprised the m-mITT cohort (322 TGC, 319 IMI/CIS) and 523 (64%) were ME (266 TGC, 256 IMI/CIS). Patients were predominantly white (88%) and male (59%) with a mean age of 49 years. The primary diagnoses for the mITT group were complicated appendicitis (41%), cholecystitis (22%), and intra-abdominal abscess (11%). For the ME population, clinical cure rates at TOC were 91.3% (242/265) for TGC versus 89.9% (232/258) for IMI/CIS (95% CI -4.0, 6.8; P<0.001). Corresponding clinical cure rates within the m-mITT population were 86.6% (279/322) for TGC versus 84.6% (270/319) for IMI/CIS (95% CI -3.7, 7.5; P<0.001 for noninferiority TGC versus IMI/CIS). The most commonly reported adverse events for TGC and IMI/CIS were nausea (17.6% TGC versus 13.3% IMI/CIS; P=0.100) and vomiting (12.6% TGC versus 9.2% IMI/CIS; P=0.144). CONCLUSIONS:TGC is efficacious in the treatment of patients with cIAIs and TGC met per the protocol-specified statistical criteria for noninferiority to the comparator, IMI/CIS.
RCT Entities:
BACKGROUND: Empiric treatment of complicated intra-abdominal infections (cIAI) represents a clinical challenge because of the diverse bacteriology and the emergence of bacterial resistance. The efficacy and safety of tigecycline (TGC), a first-in-class, expanded broad-spectrum glycylcycline antibiotic, were compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI. METHODS: In this prospective, double-blind, phase 3, multinational trial, patients were randomly assigned to intravenous (i.v.) TGC (100 mg initial dose, then 50 mg every 12 h) or i.v. IMI/CIS (500/500 mg every 6 h) for 5-14 days. Clinical response was assessed at the test-of-cure (TOC) visit (14-35 days after therapy) for microbiologically evaluable (ME) and microbiologically modified intent-to-treat (m-mITT) populations (co-primary efficacy endpoint populations in which cure/failure response rates were determined). RESULTS: Of 817 mITT patients (i.e., received > or = 1 dose of study drug), 641 (78%) comprised the m-mITT cohort (322 TGC, 319 IMI/CIS) and 523 (64%) were ME (266 TGC, 256 IMI/CIS). Patients were predominantly white (88%) and male (59%) with a mean age of 49 years. The primary diagnoses for the mITT group were complicated appendicitis (41%), cholecystitis (22%), and intra-abdominal abscess (11%). For the ME population, clinical cure rates at TOC were 91.3% (242/265) for TGC versus 89.9% (232/258) for IMI/CIS (95% CI -4.0, 6.8; P<0.001). Corresponding clinical cure rates within the m-mITT population were 86.6% (279/322) for TGC versus 84.6% (270/319) for IMI/CIS (95% CI -3.7, 7.5; P<0.001 for noninferiority TGC versus IMI/CIS). The most commonly reported adverse events for TGC and IMI/CIS were nausea (17.6% TGC versus 13.3% IMI/CIS; P=0.100) and vomiting (12.6% TGC versus 9.2% IMI/CIS; P=0.144). CONCLUSIONS:TGC is efficacious in the treatment of patients with cIAIs and TGC met per the protocol-specified statistical criteria for noninferiority to the comparator, IMI/CIS.