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

Antibiotic Resistant Infection Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04785924
• Other study ID #: IRB00081742
• Secondary ID: MISP 59805
• Status: Withdrawn
• Phase: Phase 4
• Start date: June 7, 2021
• Est. completion date: January 12, 2023

Study information

• Verified date: June 2022
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 12, 2023
• Est. primary completion date: January 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Antibiotic Resistant Infection
• Bacterial Infections
• Carbapenem-Resistant Enterobacteriaceae Infection
• Communicable Diseases
• Enterobacteriaceae Infections
• Gram-Negative Bacterial Infections
• Infections
• KPC

Intervention

Drug:
• Imipenem+Relebactam
Antibiotic treatment for KPC producing CRE-containing gram-negative infections

Locations

Country	Name	City	State
United States	Carolinas Medical Center	Charlotte	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical success	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.	30 days
Primary	Clinical success by site of infection	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.	30 days
Secondary	Mortality	Survival at 30 days	30 days
Secondary	90 day Mortality	Survival at 90 days	90 days
Secondary	Adverse effects	Incidence of nephrotoxicity, leukopenia, rash, hepatotoxicity, and seizure in treatment group	90 days
Secondary	Total Length of hospital stays	Days of hospitalization for CRE infection	90 days
Secondary	Recurrence of infection	Recurrence of CRE-containing infection within 90 days	90 days
Secondary	Development of resistance	If recurrent CRE infection develops following index infection treated with IMI/REL, then incidence of IMI/REL resistance in subsequent bacterial cultures	90 days