Effect and Safety of Meropenem–Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial

• DOI: 10.1007/s40121-018-0214-1
• Publication Date: 2018-10-01T01:56:41Z
• Authors: Richard G. Wunderink; Evangelos J. Giam...; Galia Rahav; Amy J. Mathers; Matteo Bassetti; Jose Vazquez; Oliver A. Cornely; Joseph Solomkin; Tanaya Bhowmick; Jihad Bishara; George L. Daikos; Tim Felton; Maria Jose Lopez ...; Eun Jeong Kwak; Francesco Menichetti; Ilana Oren; Elizabeth L. Alex...; David Griffith; Olga Lomovskaya; Jeffery Loutit; Shu Zhang; Michael N. Dudley; Keith S. Kaye
• Keywords: Tigecycline; Bacteremia; Ceftazidime/avibactam; Carbapenem-resistant enterobacteriaceae

Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited and CRE remain associated with high clinical failure mortality rates, particularly in vulnerable patient populations. A Phase 3, multinational, open-label, randomized controlled trial (TANGO II) was conducted from 2014 to 2017 evaluate the efficacy/safety of meropenem-vaborbactam monotherapy versus best available therapy (BAT) CRE.A total 77 patients confirmed/suspected infection (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia, complicated intra-abdominal infection, urinary tract infection/acute pyelonephritis) were randomized, 47 confirmed formed primary analysis population (microbiologic-CRE-modified intent-to-treat, mCRE-MITT). Eligible 2:1 (2 g/2 g over 3 h, q8h 7-14 days) or BAT (mono/combination polymyxins, carbapenems, aminoglycosides, tigecycline; ceftazidime-avibactam alone). Efficacy endpoints included cure, Day-28 all-cause mortality, microbiologic overall success (clinical cure + eradication). Safety adverse events (AEs) laboratory findings.Within mCRE-MITT population, rates 65.6% (21/32) 33.3% (5/15) [95% confidence interval (CI) difference, 3.3% 61.3%; P = 0.03)] at End 59.4% (19/32) 26.7% (4/15) (95% CI 4.6% 60.8%; 0.02) Test Cure;.Day-28 15.6% (5/32) - 44.7% 9.3%) BAT, respectively. Treatment-related AEs renal-related 24.0% (12/50) 4.0% (2/50) 44.0% (11/25) (6/25) BAT. Exploratory risk-benefit analyses composite nephrotoxicity favored (31.3% [10/32] 80.0% [12/15]; 95% 74.6% 22.9%; < 0.001).Monotherapy increased decreased reduced compared BAT.NCT02168946.The Medicines Company.