Clinical trial NCT04785924: 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
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Carbapenem-Resistant Enterobacteriaceae Infection
KPC
Gram-Negative Bacterial Infections
Antibiotic Resistant Infection
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-03-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Clinical success
timeFrame: 30 days
measure: Clinical success by site of infection
timeFrame: 30 days
Secondary outcomes:
measure: Mortality
timeFrame: 30 days
measure: 90 day Mortality
timeFrame: 90 days
measure: Adverse effects
timeFrame: 90 days
measure: Total Length of hospital stays
timeFrame: 90 days
measure: Recurrence of infection
timeFrame: 90 days
measure: Development of resistance
timeFrame: 90 days
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Christopher Polk, MD
role: PRINCIPAL_INVESTIGATOR
References: