1867. Meropenem-Vaborbactam vs. Best AvailableTherapy for Carbapenem-ResistantEnterobacteriaceae Infections in TANGO II: PrimaryOutcomes by Site of Infection
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
Posters
  • 1867_TANGO2_OutcomesByInfectionTypePosterIDWeek2017_100217FINAL RESIZED 90x45.pdf (441.8 kB)
  • Background: Meropenem-vaborbactam (M-V) is a beta-lactamase inhibitor combination active against Klebsiella pneumoniaecarbapenemase (KPC)-producing CRE. Few clinical trials of new agents have been conducted in patients with CRE.

    Methods:TANGO II is a randomized, Phase 3, open-label trial in patients with infections due to known or suspected CRE, including complicated urinary tract infection (cUTI), acute pyelonephritis (AP), HABP/VABP, bacteremia, or complicated intra-abdominal infection (cIAI). Eligible subjects were randomized 2:1 to monotherapy with M-V or Best Available Therapy (BAT) for 7-14 days. BAT could include (alone or in combination): a carbapenem, aminoglycoside, polymyxin B, colistin, tigecycline or ceftazidime-avibactam (monotherapy only). Enrollment was stratified by infection type and geographic region. Endpoints differed by infection: overall success (clinical cure + microbial eradication) in cUTI/AP, 28-day all-cause mortality in HABP/VABP + bacteremia, and clinical cure in cIAI. It was not powered for inferential statistical testing; results are presented descriptively.

    Results: 72 patients were enrolled: 43 (59.7%) had baseline CRE and comprised the microbiologic CRE modified intent-to-treat population (mCRE-MITT, primary population). In mCRE-MITT, 20 had bacteremia, 15 had cUTI/AP, 5 had HABP/VABP, and 3 had cIAI.

    Efficacy by Infection Type

     

    M-V (N=28)

    n/N’ (%)

    BAT (N=15)

    n/N’ (%)

    Bacteremia + HABP/VABP

    All-Cause Mortality, Day 28

    4/16 (25.0%)

    4/9 (44.4%)

    cUTI/AP

    Overall Success at End of Therapy (EOT)

    Overall Success at Test of Cure (TOC, EOT + 7 d)

    8/11 (72.7%)

    3/7 (42.9%)*

    2/4 (50%)

    2/4 (50%)

    cIAI

    Clinical Cure at TOC

    1/1 (100%)

    0/2 (0)

    *4 M-V subjects were indeterminate/not assessed at TOC.

    AEs occurred in 84.4% of M-V patients vs. 92% on BAT. M-V was associated with fewer drug-related AEs (24.4% vs. 44%), severe AEs (13.3% vs. 28%), and serious AEs (33.3% vs. 44%) vs. BAT.

    Conclusion: In this first prospective comparative trial of a beta-lactam/beta-lactamase inhibitor combination as monotherapy of CRE infections, M-V showed consistent improvement over BAT in efficacy endpoints across infections, and improved safety/tolerability. M-V appears to be an improved treatment option for CRE infections.

    Richard Wunderink, MD1, Evangelos Giamarellos-Bourboulis, MD2, Galia Rahav, MD3, Amy Mathers, MD4, Matteo Bassetti, MD, PhD5, Joseph Solomkin, MD, FIDSA6, Elizabeth Alexander, MD, MSc7, Jeffrey S. Loutit, MBChB8, Shu Zhang, PhD7, Michael N. Dudley, Pharm.D., FIDSA8 and Keith S. Kaye, MD, MPH9, (1)Northwestern University Feinberg School of Medicine, Chicago, IL, (2)Athens Medical School, Athens, Greece, (3)Sheba Medical Center, Tel Hashomer, Israel, (4)University of Virginia Health System, Charlottesville, VA, (5)San Martino Hospital, Genova, Italy, (6)University of Cincinnati, Cincinnati, OH, (7)The Medicines Company, Parsippany, NJ, (8)The Medicines Company, San Diego, CA, (9)University of Michigan Medical School, Ann Arbor, MI

    Disclosures:

    R. Wunderink, The Medicines Company: Consultant and Investigator , Consulting fee and Research grant

    E. Giamarellos-Bourboulis, None

    G. Rahav, MSD: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium
    Pfizer: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium
    Astellas: Consultant , Investigator and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium

    A. Mathers, Accelerate Diagnostics: Consultant , Consulting fee
    The Medicines Company: Consultant , Consulting fee
    Zavante Therapeutics: Research Contractor , Research support

    M. Bassetti, MSD: Consultant , Research Contractor and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium
    Pfizer: Consultant , Research Contractor and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium
    Astellas: Consultant and Speaker's Bureau , Consulting fee and Speaker honorarium
    AstraZeneca: Consultant and Speaker's Bureau , Consulting fee and Speaker honorarium
    The Medicines Company: Consultant , Consulting fee
    Tetraphase: Consultant and Speaker's Bureau , Consulting fee and Speaker honorarium
    Angelini: Consultant and Speaker's Bureau , Consulting fee and Speaker honorarium
    Basilea: Consultant and Speaker's Bureau , Consulting fee and Speaker honorarium
    Achaogen: Consultant , Consulting fee
    Paratek: Consultant , Consulting fee

    J. Solomkin, Merck: Consultant , Consulting fee
    Tetraphase: Consultant , Consulting fee
    3M: Consultant , Consulting fee
    Arsanis: Consultant , Consulting fee
    Department of Defense: Research Contractor , Research support

    E. Alexander, The Medicines Company: Shareholder , Salary

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

    S. Zhang, The Medicines Company: Shareholder , Salary

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

    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

    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.