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

NCT ID: NCT03969901

Last Updated: 2026-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-08
• Study Completion Date: 2024-05-07

Brief Summary

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.

Conditions

Suspected or Documented Gram-negative Bacterial Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IMI/REL

Participants with cIAI or cUTI will receive imipenem/cilastatin/relebactam (IMI/REL) via IV infusion for a minimum of 5 days (with optional investigator's choice of locally sourced oral switch medication after 3 days) up to a maximum of 14 days. Participants with HABP/VABP will receive IMI/REL via IV infusion for a minimum of 7 days up to a maximum of 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection will receive IMI/REL via IV infusion for 14 days. All oral switch medications will be chosen from a list of acceptable approved agents and will be administered per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines.

Group Type: EXPERIMENTAL

IMI/REL

Intervention Type: DRUG

Age-based dosing:

• 12 to <18 years, IMI 500 and REL 250 mg, IV infusion every 6 hours
• 6 to <12 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours
• 2 to <6 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours
• 3 months to <2 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours
• Birth to <3 months, IMI 15 and REL 7.5 mg/kg, IV infusion every 8 hours NOTE: Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention.

Oral Switch

Intervention Type: DRUG

All oral switch medications will be investigator's choice from a list of acceptable approved agents for infection types cIAI, and cUTI and will be given per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines. Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention.

Active Control

Participants with cIAI or cUTI will receive active control via IV infusion for a minimum of 5 days (with optional investigator's choice of locally sourced oral switch medication after 3 days) up to a maximum of 14 days. Participants with HABP/VABP will receive active control via IV infusion for a minimum of 7 days up to a maximum of 14 days. Participants with bacteremia or Pseudomonas aeruginosa infection will receive active control via IV infusion for 14 days. All active control and oral switch medications will be administered per authorized PI, SPC, or international treatment guidelines. All active control and oral switch medications will be chosen from a list of acceptable approved agents.

Group Type: ACTIVE_COMPARATOR

Active Control

Intervention Type: DRUG

All active control medications will be chosen from a list of acceptable approved agents for each infection type (HABP or VABP, cIAI, and UTI) and will be given via IV infusion, per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines.

NOTE: Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention. All oral switch medications will be chosen from a list of acceptable approved agents.

Oral Switch

Intervention Type: DRUG

All oral switch medications will be investigator's choice from a list of acceptable approved agents for infection types cIAI, and cUTI and will be given per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines. Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention.

Interventions

IMI/REL

Age-based dosing:

• 12 to <18 years, IMI 500 and REL 250 mg, IV infusion every 6 hours
• 6 to <12 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours
• 2 to <6 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours
• 3 months to <2 years, IMI 15 and REL 7.5 mg/kg, IV infusion every 6 hours
• Birth to <3 months, IMI 15 and REL 7.5 mg/kg, IV infusion every 8 hours NOTE: Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention.

Intervention Type: DRUG

Active Control

All active control medications will be chosen from a list of acceptable approved agents for each infection type (HABP or VABP, cIAI, and UTI) and will be given via IV infusion, per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines.

NOTE: Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention. All oral switch medications will be chosen from a list of acceptable approved agents.

Intervention Type: DRUG

Oral Switch

All oral switch medications will be investigator's choice from a list of acceptable approved agents for infection types cIAI, and cUTI and will be given per authorized Package Insert (PI), Summary of Product Characteristics (SPC), or international treatment guidelines. Participants with cIAI or cUTI may be switched to oral therapy after at least 3 days of IV study intervention.

Intervention Type: DRUG

Other Intervention Names

MK-7655A

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Banner University Medical Center ( Site 0356)

Tucson, Arizona, United States

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

Pan and Aglaia Kyriakou Children s Hospital ( Site 0247)

Athens, Attica, Greece

Hippokration General Hospital of Thessaloniki ( Site 0244)

Thessaloniki, , Greece

Debreceni Egyetem Klinikai Kozpont ( Site 0100)

Debrecen, Hajdú-Bihar, Hungary

Szabolcs-Szatmar-Bereg Megyei Kórházak és Egyetemi Otatókórház-Gyermekosztály ( Site 0105)

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

Rambam Medical Center ( Site 0189)

Haifa, , Israel

Hadassah Ein Karem Hebrew University Medical Center ( Site 0188)

Jerusalem, , Israel

Schneider Children's Medical Center ( Site 0187)

Petah Tikva, , Israel

Chaim Sheba Medical Center ( Site 0190)

Ramat Gan, , Israel

Hospital General de Tijuana ( Site 0284)

Tijuana, Estado de Baja California, Mexico

Hospital del Nino y Adolescente Morelense ( Site 0286)

Emiliano Zapata, Morelos, Mexico

Centenario Hospital Miguel Hidalgo-Pediatrics Department ( Site 0290)

Aguascalientes, , Mexico

Instituto Nacional de Pediatria ( Site 0291)

Mexico City, , Mexico

Haukeland Universitetssjukehus ( Site 0500)

Bergen, Hordaland, Norway

University of the Philippines-Philippine General Hospital ( Site 0318)

Manila, National Capital Region, Philippines

Philippine Children s Medical Center ( Site 0317)

Quezon City, National Capital Region, Philippines

Wojewodzki Szpital Zespolony im. Rydgiera ( Site 0220)

Torun, Kuyavian-Pomeranian Voivodeship, Poland

SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0226)

Łomianki, Masovian Voivodeship, Poland

Instytut Centrum Zdrowia Matki Polki ( Site 0223)

Lodz, Łódź Voivodeship, Poland

Pediatric Hematology Oncology and Immunology Centre n.a. D.Rogachev. ( Site 0233)

Moscow, Moscow, Russia

Morozovskaya Children City Clinical Hospital ( Site 0241)

Moscow, Moscow, Russia

State Budgetary Healthcare Institution of Novosibirsk Region City Childrens Clinical Emergency Hospi

Novosibirsk, Novosibirsk Oblast, Russia

Children s City Clinical Hospital 5 n.a. N.F. Filatov ( Site 0235)

Saint Petersburg, Sankt-Peterburg, Russia

St.Petersburg State Pediatric Medical University ( Site 0236)

Saint Petersburg, Sankt-Peterburg, Russia

Children's City Clinical Hospital #1 ( Site 0237)

Saint Petersburg, Sankt-Peterburg, Russia

Smolensk Regional Clinical Hospital ( Site 0231)

Smolensk, Smolensk Oblast, Russia

Regional Childrens Clinical Hospital ( Site 0400)

Vologda, Vologda Oblast, Russia

Empilweni Services and Research Unit ( Site 1557)

Johannesburg, Gauteng, South Africa

Chris Hani Baragwanath Academic Hospital ( Site 0156)

Johannesburg, Gauteng, South Africa

Molotlegi Street ( Site 0155)

Pretoria, Gauteng, South Africa

Hospital Infantil Universitario Nino Jesus ( Site 0114)

Madrid, , Spain

Hospital Universitario La Paz ( Site 0113)

Madrid, , Spain

Hospital Universitario Virgen del Rocio ( Site 0115)

Seville, , Spain

Cukurova University Medical Faculty ( Site 0200)

Adana, , Turkey (Türkiye)

Ankara Universitesi Tip Fakultesi. ( Site 0202)

Ankara, , Turkey (Türkiye)

Eskisehir Osmangazi University Medical ( Site 0201)

Eskişehir, , Turkey (Türkiye)

SBU Sariyer Hamidiye Etfal Egitim ve Arastirma Hastanesi ( Site 0198)

Istanbul, , Turkey (Türkiye)

Ege Universitesi Tıp Fakultesi Hastanesi ( Site 0199)

Izmir, , Turkey (Türkiye)

SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 0121)

Dnipro, Dnipropetrovsk Oblast, Ukraine

Communal non-commercial enterprise "Kryvorizka city clinical hospital 16" of Kryvyy Rig city council

Kryvyy Rig, Dnipropetrovsk Oblast, Ukraine

Ivano-Frankivsk Regional Children Clinical Hospital ( Site 0131)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

Kharkiv City Children Hospital 16 ( Site 0130)

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Municipal Enterprise Children's City Clinical Hospital in Poltava City Council ( Site 0122)

Poltava, Poltava Oblast, Ukraine

Countries

United States; Bulgaria; Chile; Colombia; Estonia; France; Greece; Hungary; Israel; Mexico; Norway; Philippines; Poland; Russia; South Africa; Spain; Turkey (Türkiye); Ukraine

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

https://www.trialsummaries.com/Study/StudyDetails?id=26857&tenant=MT_MSD_9011

Plain Language Summary

Other Identifiers

MK-7655A-021

Identifier Type: OTHER

Identifier Source: secondary_id

2019-000338-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

7655A-021

Identifier Type: -

Identifier Source: org_study_id