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Title: Randomized Trial of Ceftazidime-Avibactam vs Meropenem for Treatment of Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia (REPROVE): Analyses per US FDA-Specified End Points
Author: Torres Martí, Antoni
Rank, Doug
Melnick, David
Rekeda, Ludmyla
Chen, Xiang
Riccobene, Todd
Critchley, Ian A.
Lakkis, Hassan D.
Taylor, Dianna
Talley, Angela K.
Keywords: Pneumònia adquirida a la comunitat
Microorganismes patògens
Community-acquired pneumonia
Pathogenic microorganisms
Issue Date: 25-Apr-2019
Publisher: Oxford University Press
Abstract: Background: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP; nosocomial pneumonia) due to Gram-negative pathogens are associated with significant morbidity and mortality; treatment options for multidrug-resistant infections are limited. The pivotal phase III REPROVE trial evaluated the efficacy of ceftazidime-avibactam (CAZ-AVI) vs meropenem in the treatment of patients with HAP/VAP. Study results for prespecified analyses per US Food and Drug Administration-recommended trial end points are reported here. Methods: Hospitalized adults with HAP/VAP proven or suspected to be caused by a Gram-negative pathogen were randomized 1:1 to receive CAZ-AVI or meropenem for 7 to 14 days. The primary outcome was 28-day all-cause mortality in the intent-to-treat (ITT) population. Secondary outcomes included clinical cure at test of cure (TOC) in the ITT and microbiological ITT (micro-ITT) populations, and safety and tolerability throughout the study. Results: hundred seventy randomized patients received treatment and were included in the ITT population (CAZ-AVI, n = 436; meropenem, n = 434). CAZ-AVI was noninferior to meropenem for the primary end point (28-day all-cause mortality; ITT) based on the prespecified 10% noninferiority margin (CAZ-AVI, 9.6%; meropenem, 8.3%; difference, 1.5%; 95% confidence interval [CI], -2.4% to 5.3%) and for the clinical cure end point in the ITT population based on a prespecified -10% noninferiority margin (CAZ-AVI, 67.2%; meropenem, 69.1%; difference, −1.9%; 95% CI, -8.1% to 4.3%). Clinical cure rates at TOC for patients infected with CAZ-nonsusceptible pathogens were similar (CAZ-AVI, 75.5%; meropenem, 71.2%; micro-ITT). Safety data were consistent with established safety profiles for both agents. Conclusions: CAZ-AVI provides an important new treatment option for HAP/VAP due to Gram-negative pathogens, including CAZ-nonsusceptible strains.
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It is part of: Open Forum Infectious Diseases, 2019, vol. 6, num. 4, p. 149
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ISSN: 2328-8957
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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