Τίτλος:
Effect and Safety of Meropenem–Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Introduction: Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited and CRE infections remain associated with high clinical failure and mortality rates, particularly in vulnerable patient populations. A Phase 3, multinational, open-label, randomized controlled trial (TANGO II) was conducted from 2014 to 2017 to evaluate the efficacy/safety of meropenem–vaborbactam monotherapy versus best available therapy (BAT) for CRE. Methods: A total of 77 patients with confirmed/suspected CRE infection (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia, complicated intra-abdominal infection, complicated urinary tract infection/acute pyelonephritis) were randomized, and 47 with confirmed CRE infection formed the primary analysis population (microbiologic-CRE-modified intent-to-treat, mCRE-MITT). Eligible patients were randomized 2:1 to meropenem–vaborbactam (2 g/2 g over 3 h, q8h for 7–14 days) or BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, tigecycline; or ceftazidime-avibactam alone). Efficacy endpoints included clinical cure, Day-28 all-cause mortality, microbiologic cure, and overall success (clinical cure + microbiologic eradication). Safety endpoints included adverse events (AEs) and laboratory findings. Results: Within the mCRE-MITT population, cure rates were 65.6% (21/32) and 33.3% (5/15) [95% confidence interval (CI) of difference, 3.3% to 61.3%; P = 0.03)] at End of Treatment and 59.4% (19/32) and 26.7% (4/15) (95% CI of difference, 4.6% to 60.8%; P = 0.02) at Test of Cure;.Day-28 all-cause mortality was 15.6% (5/32) and 33.3% (5/15) (95% CI of difference, − 44.7% to 9.3%) for meropenem–vaborbactam versus BAT, respectively. Treatment-related AEs and renal-related AEs were 24.0% (12/50) and 4.0% (2/50) for meropenem–vaborbactam versus 44.0% (11/25) and 24.0% (6/25) for BAT. Exploratory risk–benefit analyses of composite clinical failure or nephrotoxicity favored meropenem–vaborbactam versus BAT (31.3% [10/32] versus 80.0% [12/15]; 95% CI of difference, − 74.6% to − 22.9%; P < 0.001). Conclusions: Monotherapy with meropenem–vaborbactam for CRE infection was associated with increased clinical cure, decreased mortality, and reduced nephrotoxicity compared with BAT. Clinical Trials Registration: NCT02168946. Funding: The Medicines Company. © 2018, The Author(s).
Συγγραφείς:
Wunderink, R.G.
Giamarellos-Bourboulis, E.J.
Rahav, G.
Mathers, A.J.
Bassetti, M.
Vazquez, J.
Cornely, O.A.
Solomkin, J.
Bhowmick, T.
Bishara, J.
Daikos, G.L.
Felton, T.
Furst, M.J.L.
Kwak, E.J.
Menichetti, F.
Oren, I.
Alexander, E.L.
Griffith, D.
Lomovskaya, O.
Loutit, J.
Zhang, S.
Dudley, M.N.
Kaye, K.S.
Περιοδικό:
Infectious Diseases and Therapy
Εκδότης:
Springer Healthcare
Λέξεις-κλειδιά:
aminoglycoside; avibactam plus ceftazidime; carbapenem; creatinine; meropenem plus vaborbactam; polymyxin; tigecycline, acute kidney failure; adult; anemia; antimicrobial therapy; Article; bacteremia; bacterium isolation; carbapenem-resistant Enterobacteriaceae; controlled study; diarrhea; disk diffusion; drug efficacy; drug safety; drug withdrawal; Enterobacteriaceae infection; female; human; hypokalemia; hypotension; Klebsiella pneumoniae; major clinical study; male; MIC50; monotherapy; mortality; multicenter study; nephrotoxicity; phase 3 clinical trial; priority journal; prospective study; randomized controlled trial; risk benefit analysis; septic shock; treatment failure
DOI:
10.1007/s40121-018-0214-1
