search
Back to results

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

Primary Purpose

Carbapenem-Resistant Enterobacteriaceae Infection, KPC, Gram-Negative Bacterial Infections

Status
Withdrawn
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Imipenem+Relebactam
Sponsored by
Wake Forest University Health Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carbapenem-Resistant Enterobacteriaceae Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Carolinas Medical Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Observation Treatment Group

Arm Description

All patients observed while treated with IMI/REL.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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

Full Information

First Posted
March 2, 2021
Last Updated
January 13, 2023
Sponsor
Wake Forest University Health Sciences
Collaborators
Merck Sharp & Dohme LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT04785924
Brief Title
Imipenem/Cilastatin/Relebactam (IMI/REL) in Treatment of CRE Infections
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of enrollment
Study Start Date
June 7, 2021 (Actual)
Primary Completion Date
January 12, 2023 (Actual)
Study Completion Date
January 12, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

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
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carbapenem-Resistant Enterobacteriaceae Infection, KPC, Gram-Negative Bacterial Infections, Antibiotic Resistant Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Observation Treatment Group
Arm Type
Other
Arm Description
All patients observed while treated with IMI/REL.
Intervention Type
Drug
Intervention Name(s)
Imipenem+Relebactam
Other Intervention Name(s)
Recarbrio
Intervention Description
Antibiotic treatment for KPC producing CRE-containing gram-negative infections
Primary Outcome Measure Information:
Title
Clinical success
Description
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.
Time Frame
30 days
Title
Clinical success by site of infection
Description
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.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Mortality
Description
Survival at 30 days
Time Frame
30 days
Title
90 day Mortality
Description
Survival at 90 days
Time Frame
90 days
Title
Adverse effects
Description
Incidence of nephrotoxicity, leukopenia, rash, hepatotoxicity, and seizure in treatment group
Time Frame
90 days
Title
Total Length of hospital stays
Description
Days of hospitalization for CRE infection
Time Frame
90 days
Title
Recurrence of infection
Description
Recurrence of CRE-containing infection within 90 days
Time Frame
90 days
Title
Development of resistance
Description
If recurrent CRE infection develops following index infection treated with IMI/REL, then incidence of IMI/REL resistance in subsequent bacterial cultures
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Bacterial infection with Enterobacteriaceae excluding Morganellaceae Ability and willingness to give informed consent. A Legal authorized representative may be used when the patient is unable to provide informed consent. 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: 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. Infections localized to urinary source alone (bloodstream infections from urinary source will be included) Infection with Morganellaceae Prior serious allergic reaction to carbapenem therapy Need for ongoing concomitant therapy with ganciclovir or valproic acid 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. 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. Inability to comply with study protocol or remain hospitalized for duration of study. Life expectancy less than 72 hours in opinion of study investigators.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Polk, MD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs