1879. Meropenem-Vaborbactam: Outcomes in Subjects with Renal Impairment in Phase 3 Studies TANGO I and II
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
Posters
  • 1879_TANGO1and2RenalImpairmentPosterIDWeek2017_100517Resized45x90.pdf (584.4 kB)
  • Background:Meropenem-vaborbactam (M-V) is being developed to treat serious gram-negative infections, which often occur in patients with renal impairment. Studies of some recently approved beta-lactamase inhibitor combination products reported reduced clinical response in patients with renal impairment. The purpose of this study was to compare clinical response in patients enrolled in M-V Phase 3 studies.

    Methods: TANGO I was a Phase 3, multicenter, double-blind, randomized study evaluating M-V vs. piperacillin-tazobactam (P-T) for the treatment of complicated urinary tract infection (cUTI) or acute pyelonephritis (AP). TANGO II was a randomized, open-label trial of M-V vs. Best Available Therapy (BAT) in patients with serious infections, including cUTI, AP, HABP/VABP, bacteremia, or cIAI, due to known or suspected CRE. M-V dosage was adjusted in patients with creatinine clearances <50 mL/min in both studies. Outcomes were compared according to baseline renal function calculated using the Cockcroft-Gault equation.

    Results:  In TANGO I, 374 subjects had a baseline pathogen and were included in the m-MITT population, and in TANGO II, 43 subjects had a baseline CRE organism and were included in the mCRE-MITT population. 44/374 (11.8%) and 9/43 (20.9%) subjects had a baseline creatinine clearance (CrCl) <50 mL/min, respectively. Outcomes by treatment group at the End of IV Therapy (EOIVT) were assessed; overall success (clinical cure and eradication) in TANGO I and clinical outcome across all infection types in TANGO II are presented:

    Table: Outcomes at EOIVT by Baseline CrCl

    TANGO I (m-MITT)

    TANGO II (mCRE-MITT)

    Overall Success at EOIVT

    Clinical Cure Across All Indications
    at EOIVT

    Baseline CrCl

    M-V

    P-T

    M-V

    BAT

    ≥50 mL/min

    166/169 (98.2%)

    148/157 (94.3%)

    15/22 (68.2%)

    4/9 (44.4%)

    <50 mL/min

    21/21 (100%)

    20/22 (90.9%)

    2/5 (40%)

    1/4 (25%)

    The outcomes for P-T in TANGO I and M-V in TANGO I and TANGO II were comparable in subjects with baseline CrCl ≥50 mL/min and <50 mL/min. Outcomes with M-V were higher compared to those observed for the control regimens in each study.

    Conclusion:In TANGO I and II, M-V efficacy at EOIVT was comparable in patients with baseline CrCl <50 mL/min requiring a M-V dose adjustment and those with baseline CrCl ≥50 mL/min.

    Amy Mathers, MD1, William Hope, BMBS, FRACP, FRCPA, PhD2, Keith S. Kaye, MD, MPH3, Jeffrey S. Loutit, MBChB4, Elizabeth Alexander, MD, MSc5, Michael N. Dudley, Pharm.D., FIDSA4 and Jose Vazquez, MD, FACP, FIDSA6, (1)University of Virginia Health System, Charlottesville, VA, (2)University of Liverpool, Liverpool, United Kingdom, (3)University of Michigan Medical School, Ann Arbor, MI, (4)The Medicines Company, San Diego, CA, (5)The Medicines Company, Parsippany, NJ, (6)Henry Ford Hospital, Detroit, MI

    Disclosures:

    A. Mathers, None

    W. Hope, None

    K. S. Kaye, Xellia: Consultant , Consulting fee
    Merck: Consultant and Grant Investigator , Consulting fee and Research support
    The Medicines Company: Consultant and Grant Investigator , Consulting fee and Research support

    J. S. Loutit, The Medicine's Company: Employee and Shareholder , Salary

    E. Alexander, The Medicines Company: Shareholder , Salary

    M. N. Dudley, The Medicine's Company: Employee and Shareholder , Salary

    J. Vazquez, None

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.