Safety, Tolerability, Efficacy and Pharmacokinetics of Imipenem/Cilastatin/Relebactam (MK-7655A) in Pediatric Participants With Gram-negative Bacterial Infection (MK-7655A-021)
Suspected or Documented Gram-negative Bacterial Infection
About this trial
This is an interventional treatment trial for Suspected or Documented Gram-negative Bacterial Infection
Eligibility Criteria
Inclusion Criteria:
- Requires hospitalization and treatment with 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: HABP or VABP; cIAI; or cUTI.
- For Age Cohorts 4 and 5, participant is at least 37 weeks postmenstrual age at the time of signing the informed consent.
- 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 (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.
- 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 (ie, requiring a permanent indwelling urinary catheter or instrumentation); documented ileal loop reflux; 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 (eg, anaphylaxis), or any serious reaction to IMI, or to any carbapenem, cephalosporin, penicillin, or other β-lactam agent, or to other β-lactamase inhibitors (eg, 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 until meningitis has been ruled out prior to initiation of IV study intervention.
- If 3 months of age or older, has received potentially therapeutic antibacterial therapy (eg, 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 (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.
Sites / Locations
- Banner University Medical Center ( Site 0356)
- Miller Children's & Women's Hospital ( Site 0349)
- Rady Children's Hospital-San Diego ( Site 0347)Recruiting
- Tufts Medical Center-Floating Hospital for Children ( Site 0350)
- University of New Mexico ( Site 0358)
- University Hospital ( Site 0360)Recruiting
- Children's Hospital of Richmond at VCU ( Site 0359)
- West Virginia University Ruby Memorial Hospital ( Site 0344)Recruiting
- UMHAT Deva Maria. EOOD ( Site 0165)Recruiting
- MHAT City Clinic Sv. Georgi EOOD ( Site 0167)
- UMHAT Dr. Georgi Stranski EAD ( Site 0174)
- UMHAT Kanev AD ( Site 0168)Recruiting
- UMHAT Kanev AD ( Site 0169)Recruiting
- MHAT Dr. Ival Seliminski ( Site 0173)
- Hospital Roberto del Río ( Site 0802)Recruiting
- Fundacion Hospital San Vicente de Paul ( Site 0269)
- Clinica de la Costa S.A.S. ( Site 0264)Recruiting
- Sociedad de Cirugía de Bogotá - Hospital de San Jose ( Site 0265)Recruiting
- Fundacion Hospital Infantil Universitario de San Jose ( Site 0268)Recruiting
- Fundacion Valle del Lili ( Site 0266)Recruiting
- Tallinn Children Hospital ( Site 0209)Recruiting
- Hopitaux Pediatriques CHU Lenval ( Site 0143)Recruiting
- Hopital Francois Mitterand ( Site 0146)
- Hopital Jeanne de Flandre ( Site 0145)Recruiting
- University of Athens - Aghia Sophia Childrens Hospital ( Site 0243)Recruiting
- Pan and Aglaia Kyriakou Children s Hospital ( Site 0247)Recruiting
- Hippokration General Hospital of Thessaloniki ( Site 0244)Recruiting
- Debreceni Egyetem Klinikai Kozpont ( Site 0100)Recruiting
- Szabolcs-Szatmar-Bereg Megyei Kórházak és Egyetemi Otatókórház-Gyermekosztály ( Site 0105)Recruiting
- Rambam Medical Center ( Site 0189)Recruiting
- Hadassah Ein Karem Hebrew University Medical Center ( Site 0188)Recruiting
- Schneider Children's Medical Center ( Site 0187)
- Chaim Sheba Medical Center ( Site 0190)Recruiting
- Hospital General de Tijuana ( Site 0284)
- Hospital del Nino y Adolescente Morelense ( Site 0286)
- Centenario Hospital Miguel Hidalgo-Pediatrics Department ( Site 0290)Recruiting
- Instituto Nacional de Pediatria ( Site 0291)Recruiting
- Haukeland Universitetssjukehus ( Site 0500)Recruiting
- University of the Philippines-Philippine General Hospital ( Site 0318)
- Philippine Children s Medical Center ( Site 0317)
- Wojewodzki Szpital Zespolony im. Rydgiera ( Site 0220)Recruiting
- Instytut Centrum Zdrowia Matki Polki ( Site 0223)Recruiting
- SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0226)Recruiting
- Pediatric Hematology Oncology and Immunology Centre n.a. D.Rogachev. ( Site 0233)
- Morozovskaya Children City Clinical Hospital ( Site 0241)
- State Budgetary Healthcare Institution of Novosibirsk Region City Childrens Clinical Emergency Hospi
- St.Petersburg State Pediatric Medical University ( Site 0236)
- Children's City Clinical Hospital #1 ( Site 0237)
- Children s City Clinical Hospital 5 n.a. N.F. Filatov ( Site 0235)
- Smolensk Regional Clinical Hospital ( Site 0231)
- Regional Childrens Clinical Hospital ( Site 0400)
- Empilweni Services and Research Unit ( Site 1557)
- Chris Hani Baragwanath Academic Hospital ( Site 0156)Recruiting
- Molotlegi Street ( Site 0155)Recruiting
- Hospital Infantil Universitario Nino Jesus ( Site 0114)Recruiting
- Hospital Universitario La Paz ( Site 0113)
- Hospital Universitario Virgen del Rocio ( Site 0115)Recruiting
- Cukurova University Medical Faculty ( Site 0200)Recruiting
- Ankara Universitesi Tip Fakultesi. ( Site 0202)
- Eskisehir Osmangazi University Medical ( Site 0201)Recruiting
- SBU Sariyer Hamidiye Etfal Egitim ve Arastirma Hastanesi ( Site 0198)Recruiting
- Ege Universitesi Tıp Fakultesi Hastanesi ( Site 0199)
- SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 0121)
- PI Kryvorizka city clinical hospital 8 of Dnipropetrovsk Reg Council ( Site 0128)
- Ivano-Frankivsk Regional Children Clinical Hospital ( Site 0131)
- Kharkiv City Children Hospital 16 ( Site 0130)
- Municipal Enterprise Children's City Clinical Hospital in Poltava City Council ( Site 0122)
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
IMI/REL
Active Control
Participants with cIAI or cUTI will receive imipenem/cilastatin/relebactam (IMI/REL) via IV infusion, once every 6 hours, for a minimum of 5 days (with optional oral switch after 3 days) up to a maximum of 14 days. Participants with HABP/VABP will receive IMI/REL via IV infusion, once every 6 hours, for a minimum of 7 days up to a maximum of 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.
Participants with cIAI or cUTI will receive active control via IV infusion for a minimum of 5 days (with optional oral switch 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. 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.