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

Phase 4

Withdrawn

• Conditions: Carbapenem-Resistant Enterobacteriaceae Infection; Gram-Negative Bacterial Infections; KPC; Antibiotic Resistant Infection
• Interventions: Drug: Imipenem+Relebactam

• Registration Number: NCT04785924
• Lead Sponsor: Wake Forest University Health Sciences

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-03-02
• Study First Submitted QC: 2021-03-03
• Study First Posted: 2021-03-08
• Study Start: 2021-06-07
• Status Verified: 2022-06
• Primary Completion: 2023-01-12
• Study Completion: 2023-01-12
• Last Update Submitted: 2023-01-13
• Last Update Posted: 2023-01-17

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Observation Treatment Group	Imipenem+Relebactam	All patients observed while treated with IMI/REL.

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures

Name	Time	Method
Mortality	30 days	Survival at 30 days
Recurrence of infection	90 days	Recurrence of CRE-containing infection within 90 days
90 day Mortality	90 days	Survival at 90 days
Total Length of hospital stays	90 days	Days of hospitalization for CRE infection
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
Adverse effects	90 days	Incidence of nephrotoxicity, leukopenia, rash, hepatotoxicity, and seizure in treatment group

Trial Locations

Locations (1)

Carolinas Medical Center; 🇺🇸 Charlotte, North Carolina, United States