Efficacy and safety of tigecycline monotherapy vs. imipenem/cilastatin in Chinese patients with complicated intra-abdominal infections: a randomized controlled trial.
Author(s): Chen Z, Wu J, Zhang Y, Wei J, Leng X, Bi J, Li R, Yan L, Quan Z, Chen X, Yu Y, Wu Z, Liu D, Ma X, Maroko R, Cooper A
Affiliation(s): Huashan Hospital, Fudan University, Shanghai, China.
Publication date & source: 2010-07-21, BMC Infect Dis., 10:217.
Publication type: Clinical Trial, Phase III; Comparative Study; Multicenter Study; Randomized Controlled Trial
BACKGROUND: Tigecycline, a first-in-class broad-spectrum glycylcycline antibiotic, has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections (cIAIs), including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria. In the current trial, tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs. METHODS: In this phase 3, multicenter, open-label study, patients were randomly assigned to receive IV tigecycline or imipenem/cilastatin for </=2 weeks. The primary efficacy endpoints were clinical response at the test-of-cure visit (12-37 days after therapy) for the microbiologic modified intent-to-treat and microbiologically evaluable populations. Because the study was not powered to demonstrate non-inferiority between tigecycline and imipenem/cilastatin, no formal statistical analysis was performed. Two-sided 95% confidence intervals (CIs) were calculated for the response rates in each treatment group and for differences between treatment groups for descriptive purposes. RESULTS: One hundred ninety-nine patients received >/=1 dose of study drug and comprised the modified intent-to-treat population. In the microbiologically evaluable population, 86.5% (45 of 52) of tigecycline- and 97.9% (47 of 48) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment (12-37 days after therapy); in the microbiologic modified intent-to-treat population, cure rates were 81.7% (49 of 60) and 90.9% (50 of 55), respectively. The overall incidence of treatment-emergent adverse events was 80.4% for tigecycline vs. 53.9% after imipenem/cilastatin therapy (P < 0.001), primarily due to gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; P < 0.001) and vomiting (12.4% vs. 2.0%; P = 0.005). CONCLUSIONS: Clinical cure rates for tigecycline were consistent with those found in global cIAI studies. The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI, as well as that observed in analyses of Chinese patients in those studies; no novel trends were observed. TRIAL REGISTRATION: ClinicalTrials.gov NCT00136201.