Ceftazidime-Avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program.
Clin Infect Dis. 2016 Jun 16;
Authors: Wagenlehner FM, Sobel JD, Newell P, Armstrong J, Huang X, Stone G, Yates K, Gasink LB
Abstract
BACKGROUND: The global emergence of carbapenem-resistant Enterobacteriaceae highlights the urgent need to reduce carbapenem dependence. The phase 3 RECAPTURE program compared the efficacy and safety of ceftazidime-avibactam and doripenem in patients with complicated urinary tract infection (cUTI), including acute pyelonephritis.
METHODS: Hospitalized adults with suspected/microbiologically-confirmed cUTI/acute pyelonephritis were randomized 1:1 to ceftazidime-avibactam 2000-500 mg every 8 hours (q8h) or doripenem 500 mg q8h (doses adjusted for renal function) with possible oral antibiotic switch after ≥5 days (total treatment duration up to 10 days or 14 days for patients with bacteremia).
RESULTS: Of 1033 randomized patients, 393 and 417 treated with ceftazidime-avibactam and doripenem respectively were eligible for the primary efficacy analyses; 19.6% had ceftazidime-non-susceptible baseline pathogens. Non-inferiority of ceftazidime-avibactam versus doripenem was demonstrated for the FDA co-primary endpoints of (1) patient-reported symptomatic resolution at Day 5: 276/393 (70.2%) versus 276/417 (66.2%) patients (difference 4.0% [95% CI, -2.39% to 10.42%]); and (2) combined symptomatic resolution/microbiological eradication at test-of-cure (TOC): 280/393 (71.2%) versus 269/417 (64.5%) patients (difference 6.7% [95% CI, 0.30% to 13.12%]). Microbiological eradication at TOC (EMA primary endpoint) occurred in 304/393 (77.4%) ceftazidime-avibactam versus 296/417 (71.0%) doripenem patients (difference 6.4% [95% CI, 0.33% to 12.36%]), demonstrating superiority at the 5% significance level. Both treatments showed similar efficacy against ceftazidime-non-susceptible pathogens. Ceftazidime-avibactam had a safety profile consistent with ceftazidime alone.
CONCLUSIONS: Ceftazidime-avibactam was highly effective for the empiric treatment of cUTI (including acute pyelonephritis), and may offer an alternative to carbapenems in this setting.
CLINICAL TRIALS REGISTRATION: NCT01595438 and NCT01599806.
PMID: 27313268 [PubMed - as supplied by publisher]