Systematic review and meta-analysis of antimicrobial treatment effect estimation in complicated urinary tract infection.
Noninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of three potential active comparator drugs for the design of a noninferiority trial. The systematic review identified no placebo trials of cUTI, four clinical trials of cUTI with uncomplicated urinary tract infection as a proxy for placebo, and nine trials with reports of treatment effect estimates for doripenem, levofloxacin, or imipenem-cilastatin. In the meta-analysis, the primary efficacy endpoint of interest was the microbiological eradication rate at the test-of-cure visit in the microbiological intent-to-treat population. The estimated eradication rates and corresponding 95% confidence intervals (CI) were 31.8% (26.5% to 37.2%) for placebo, 81% (77.7% to 84.2%) for doripenem, 79% (75.9% to 82.2%) for levofloxacin, and 80.5% (71.9% to 89.1%) for imipenem-cilastatin. The treatment effect estimates were 40.5% for doripenem, 38.7% for levofloxacin, 34.7% for imipenem-cilastatin, and 40.8% overall. These treatment effect estimates can be used to inform the design and analysis of future noninferiority trials in cUTI study populations.
GlaxoSmithKline, Collegeville, Pennsylvania, USA.
Krishan P
KP
Singh
Gang
G
Li
Fanny S
FS
Mitrani-Gold
Milena
M
Kurtinecz
Jeffrey
J
Wetherington
John F
JF
Tomayko
Linda M
LM
Mundy
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015780:Carbapenems / Q000627:therapeutic use*; D015377:Cilastatin / Q000627:therapeutic use*; D000077728:Cilastatin, Imipenem Drug Combination; D002986:Clinical Trials as Topic; D016206:Databases, Bibliographic; D000077726:Doripenem; D004338:Drug Combinations; D005260:Female; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use*; D064704:Levofloxacin / Q000627:therapeutic use*; D008297:Male; D012107:Research Design; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004338:Drug Combinations; D015377:Cilastatin; D064704:Levofloxacin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D000077726:Doripenem