Imipenem/Cilastatin/Relebactam (IMI/REL) in Treatment of CRE Infections

Sponsor
Wake Forest University Health Sciences (Other)
Overall Status
Recruiting
CT.gov ID
NCT04785924
Collaborator
Merck Sharp & Dohme LLC (Industry)
15
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1
27.8
0.5

Study Details

Study Description

Brief Summary

This is an observation study comparing prospective use of Imipenem/Cilastatin/Relebactam (IMI/REL) to retrospective data using Meropenem/Vabobactam (MVB)and Ceftazidime/Avibactam CZA) in treatment of Klebsiella Producing Carbapenemase Enterobacteriaceae infections at a tertiary care hospital. The objectives of the study are to demonstrate successful treatment of KPC containing Enterobacteriaceae infections with IMI/REL including in bacteremia, and to analyze treatment outcomes in use of IMI/REL for KPC-producing infections compared to historical clinical outcome data with CZA and MVB use at the same institution.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
15 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
A study of outcomes with use of an antibiotic, IMI/REL which can be compared with retrospective data of CRE-containing infections treated with MVB and CZA.A study of outcomes with use of an antibiotic, IMI/REL which can be compared with retrospective data of CRE-containing infections treated with MVB and CZA.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Study Comparing Prospective Use of Imipenem/Cilastatin/Relebactam (IMI/REL) to Retrospective Data Using Meropenem/ Vabobactam (MVB) and Ceftazidime/Avibactam (CZA) in Treatment of Klebsiella Producing Carbapenemase Enterobacteriaceae Infections
Actual Study Start Date :
Jun 7, 2021
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Oct 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Other: Observation Treatment Group

All patients observed while treated with IMI/REL.

Drug: Imipenem+Relebactam
Antibiotic treatment for KPC producing CRE-containing gram-negative infections
Other Names:
  • Recarbrio
  • Outcome Measures

    Primary Outcome Measures

    1. Clinical success [30 days]

      Clinical success defined as survival at 30 days, resolution of signs and symptoms of infection, sterilization of blood cultures within 7 days of treatment initiation in patients with bacteremia, and absence of recurrent infections.

    2. Clinical success by site of infection [30 days]

      Clinical success in patients grouped by site of infection: bacteremia, respiratory, intra-abdominal infection, soft tissue, catheter associated and urinary tract. Subjects may be included in multiple groups if applicable for analysis.

    Secondary Outcome Measures

    1. Mortality [30 days]

      Survival at 30 days

    2. 90 day Mortality [90 days]

      Survival at 90 days

    3. Adverse effects [90 days]

      Incidence of nephrotoxicity, leukopenia, rash, hepatotoxicity, and seizure in treatment group

    4. Total Length of hospital stays [90 days]

      Days of hospitalization for CRE infection

    5. Recurrence of infection [90 days]

      Recurrence of CRE-containing infection within 90 days

    6. Development of resistance [90 days]

      If recurrent CRE infection develops following index infection treated with IMI/REL, then incidence of IMI/REL resistance in subsequent bacterial cultures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Adult (>18 years of age) patients with a KPC-producing CRE infection at any site except for isolated urinary source. Patients may be initially enrolled once identified with a CRE infection defined as resistance to any carbapenem. Any carbapenem resistance will provide an initial mechanism of identifying study eligible patients in accordance with our institutions definition of CRE for infection prevention purposes. As this study is specific for KPC-producing CRE inclusion in the study analysis will require confirmation of a KPC gene by molecular analysis of the isolate and subjects enrolled may be subsequently removed from study and excluded from analysis if molecular testing reveals their CRE isolate to be a non-KPC mechanism of resistance. Polymicrobial infections at same or different sites can also be included as long as additional gram-negative active agents aside from IMI/REL are not needed for treatment.

    2. Bacterial infection with Enterobacteriaceae excluding Morganellaceae

    3. Ability and willingness to give informed consent. A Legal authorized representative may be used when the patient is unable to provide informed consent.

    4. Be the first episode of a CRE infection to be treated with IMI/REL. Previously treatment with IMI/REL for a KPC-containing Enterobacteriaceae infection will exclude patients from enrollment.

    Exclusion Criteria:
    1. Receipt of more than 48 hours of effective antibiotic therapy against KPC containing infections (e.g. MVB, CZA) prior to first dose of IMI/REL being administered.

    2. Infections localized to urinary source alone (bloodstream infections from urinary source will be included)

    3. Infection with Morganellaceae

    4. Prior serious allergic reaction to carbapenem therapy

    5. Need for ongoing concomitant therapy with ganciclovir or valproic acid

    6. Need for ongoing concomitant therapy with another antibiotic active against gram negative pathogens. Concomitant therapy with Vancomycin, Daptomycin, Linezolid, Clindamycin, Fidaxomicin, Nafcillin, Metronidazole, and Rifaximin will be allowed but no other antibiotic agents.

    7. Pregnancy or ongoing breastfeeding. Women of childbearing age must test negative on a urine pregnancy test at time of screening for trial eligibility and remain either abstinent or use 2 forms of highly effective contraception for the duration of the IMI/REL administration during the study.

    8. Inability to comply with study protocol or remain hospitalized for duration of study.

    9. Life expectancy less than 72 hours in opinion of study investigators.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Carolinas Medical Center Charlotte North Carolina United States 28203

    Sponsors and Collaborators

    • Wake Forest University Health Sciences
    • Merck Sharp & Dohme LLC

    Investigators

    • Principal Investigator: Christopher Polk, MD, Wake Forest University Health Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Wake Forest University Health Sciences
    ClinicalTrials.gov Identifier:
    NCT04785924
    Other Study ID Numbers:
    • IRB00081742
    • MISP 59805
    First Posted:
    Mar 8, 2021
    Last Update Posted:
    Jun 21, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jun 21, 2022