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, BMC Infect Dis. , 10:217
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.
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