Safety, Tolerability, Efficacy and Pharmacokinetics of Imipenem/Cilastatin/Relebactam (MK-7655A) in Pediatric Participants With Gram-negative Bacterial Infection (MK-7655A-021)

Completed · Phase 2/Phase 3

Conditions studied: Suspected or Documented Gram-negative Bacterial Infection

In brief

The primary purpose of this study is to evaluate the safety and tolerability of imipenem/cilastatin/relebactam (IMI/REL) in participants from birth to less than 18 years of age with confirmed or suspected gram-negative bacterial infection. Participants are expected to require hospitalization through completion of intravenous (IV) study intervention, and have at least one of the following primary infection types: hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP); complicated intra-abdominal infection (cIAI); or complicated urinary tract infection (cUTI). Participants will be randomized in a 3:1 ratio to receive IMI/REL or active control. This study will also evaluate the efficacy of IMI/REL by assessing all-cause mortality at Day 28 post-randomization, as well as clinical and microbiological response to treatment. It will also evaluate the pharmacokinetics of IMI/REL.

Key facts

Study ID: NCT03969901
Run by: Merck Sharp & Dohme LLC
People needed: 115
Starts: 2019-10-08
Expected to finish: 2024-05-07
Last updated by the study team: 2026-02-05

Who can join

Age: any, up to 17. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Inclusion Criteria include but are not limited to:
Requires hospitalization and treatment with intravenous (IV) antibacterial therapy for confirmed or suspected gram-negative bacterial infection (in the absence of meningitis), and is expected to require hospitalization through completion of IV study intervention, with at least 1 of the following primary infection types: Hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP); complicated intra-abdominal infection (cIAI); or complicated urinary tract infection (cUTI).
For Age Cohorts 4 and 5, participant is at least 37 weeks postmenstrual age at the time of signing the informed consent/assent.
If female, must not be pregnant or breastfeeding, and at least 1 of the following conditions must apply: must not be a woman of childbearing potential (WOCBP); OR, if a WOCBP, must agree to follow contraceptive guidance during the intervention period and for at least 24 hours after the last dose of study intervention.
Has sufficient intravascular access to receive study drug through an existing peripheral or central line.

You may not qualify if…

Exclusion Criteria include but are not limited to:
Is expected to survive less than 72 hours.
Has a concurrent infection that would interfere with evaluation of response to the study antibacterials (imipenem/cilastatin/relebactam (IMI/REL) or Active Control), including any of the following: endocarditis; osteomyelitis; meningitis; prosthetic joint infection; active pulmonary tuberculosis; disseminated fungal infection; concomitant infection at the time of randomization that requires non-study systemic antibacterial therapy in addition to IV study treatment or oral step-down therapy (medications with only gram-positive activity [e.g., vancomycin, linezolid] are allowed).
Has HABP/VABP caused by an obstructive process, including lung cancer (or other malignancy metastatic to the lungs resulting in pulmonary obstruction) or other known obstruction.
Has a cUTI, with any of the following: complete obstruction of any portion of the urinary tract (i.e., requiring a permanent indwelling urinary catheter or instrumentation); documented reflux of ileal loop urinary diversion; suspected or confirmed perinephric or intrarenal abscess; suspected or confirmed prostatitis, urethritis, or epididymitis; trauma to pelvis/urinary tract; presence of indwelling urinary catheter which cannot be removed at study entry.
Has any of the following medical conditions at screening: history of a seizure disorder (requiring ongoing treatment with anti-convulsive therapy or prior treatment with anti-convulsive therapy within the last 3 years); cystic fibrosis; history of serious allergy, hypersensitivity (e.g., anaphylaxis), or any serious reaction to IMI, or to any carbapenem, cephalosporin, penicillin, or other β-lactam agent, or to other β-lactamase inhibitors (e.g., tazobactam, sulbactam, clavulanic acid, avibactam).
Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might expose the participant to risk by participating in the study, confound study results, or interfere with the participant's participation for the full duration of the study.
If less than 3 months of age, has received more than 72 hours of empiric antibacterial treatment for suspected meningitis prior to initiation of IV study intervention.
For all Age Cohorts, provided all other eligibility criteria are met, the following participants may be enrolled:
A participant failing prior antibiotic therapy for a current episode of cUTI or HABP/VABP who: Has received the prior antibacterial treatment for at least 48 hours; Has persistent clinical or radiographic findings clearly indicating ongoing infection; Fulfills other laboratory or microbiology criteria for enrollment
A participant failing prior antibiotic therapy for a current episode of cIAI who: Has received the prior antibacterial treatment for at least 48 hours; Has persistent clinical or radiographic findings clearly indicating ongoing infection; Fulfills other laboratory or microbiology criteria for enrollment; Has planned operative intervention no more than 24 hours after first dose of study treatment; Has not received any further nonstudy antibiotics postoperatively
If 3 months of age or older, or <3 months of age without suspected meningitis, has received potentially therapeutic antibacterial therapy (e.g., with gram-negative activity), including bladder infusions with topical urinary antiseptics or antibacterial agents, for a duration of more than 24 hours during the 48 hours preceding the first dose of study intervention.
Is anticipated to be treated with any of the following medications: valproic acid or divalproex sodium (or has used valproic acid or divalproex sodium in the 2 weeks prior to screening) through 24 hours after completion of the final dose of IV study intervention for participants who receive IMI/REL or carbapenem; concomitant IV, oral, or inhaled antimicrobial agents with gram-negative activity, in addition to those designated in the study intervention groups, during the course of all (IV/oral) study intervention; planned receipt of suppressive/prophylactic antibiotics with gram-negative activity after completion of study intervention.
Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 30 days prior to screening.
Has enrolled previously in the current study and been discontinued or has received REL for any other reason.
Has an estimated creatinine clearance (based on the Cockcroft-Gault equation, for participants ≥12 years of age or estimated glomerular filtration rate (eGFR), based on the modified Schwartz equation, for participants <12 years of age below that specified for the appropriate age range; or requires peritoneal dialysis, hemodialysis, or hemofiltration.
Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥5 × upper limit of normal (ULN) at the time of screening. NOTE: Patients with acute hepatic failure or acute decompensation of chronic hepatic failure should also be excluded.
Is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence.
Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.

Where it is running

Miller Children's & Women's Hospital ( Site 0349) — Long Beach, California, United States
Rady Children's Hospital-San Diego ( Site 0347) — San Diego, California, United States
Tufts Medical Center-Floating Hospital for Children ( Site 0350) — Boston, Massachusetts, United States
University of New Mexico ( Site 0358) — Albuquerque, New Mexico, United States
University Hospital ( Site 0360) — San Antonio, Texas, United States
Children's Hospital of Richmond at VCU ( Site 0359) — Richmond, Virginia, United States
West Virginia University Ruby Memorial Hospital ( Site 0344) — Morgantown, West Virginia, United States
UMHAT Deva Maria. EOOD ( Site 0165) — Burgas, Bulgaria
MHAT City Clinic Sv. Georgi EOOD ( Site 0167) — Montana, Bulgaria
UMHAT Dr. Georgi Stranski EAD ( Site 0174) — Pleven, Bulgaria
UMHAT Kanev AD ( Site 0168) — Rousse, Bulgaria
UMHAT Kanev AD ( Site 0169) — Rousse, Bulgaria
MHAT Dr. Ival Seliminski ( Site 0173) — Sliven, Bulgaria
Hospital Roberto del Río ( Site 0802) — Santiago, Region M. de Santiago, Chile
Fundacion Hospital San Vicente de Paul ( Site 0269) — Medellín, Antioquia, Colombia
Clinica de la Costa S.A.S. ( Site 0264) — Barranquilla, Atlántico, Colombia
Sociedad de Cirugía de Bogotá - Hospital de San Jose ( Site 0265) — Bogotá, Bogota D.C., Colombia
Fundacion Hospital Infantil Universitario de San Jose ( Site 0268) — Bogotá, Bogota D.C., Colombia
Fundacion Valle del Lili ( Site 0266) — Cali, Valle del Cauca Department, Colombia
Tallinn Children Hospital ( Site 0209) — Tallinn, Harju, Estonia
Hopitaux Pediatriques CHU Lenval ( Site 0143) — Nice, Alpes-Maritimes, France
Hopital Francois Mitterand ( Site 0146) — Dijon, Cote-d Or, France
Hopital Jeanne de Flandre ( Site 0145) — Lille, Hauts-de-France, France
University of Athens - Aghia Sophia Childrens Hospital ( Site 0243) — Athens, Attica, Greece
Banner University Medical Center ( Site 0356) — Tucson, Arizona, United States

Full record on ClinicalTrials.gov

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