search
Back to results

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

Primary Purpose

Suspected or Documented Gram-negative Bacterial Infection

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IMI/REL
Active Control
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Suspected or Documented Gram-negative Bacterial Infection

Eligibility Criteria

undefined - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Arm Type

Experimental

Active Comparator

Arm Label

IMI/REL

Active Control

Arm Description

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.

Outcomes

Primary Outcome Measures

Percentage of Participants With One or More Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with AEs will be presented.
Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study medication due to an AE will be presented.

Secondary Outcome Measures

Number of Deaths by All Causes Through Day 28
All-cause mortality up to 28 days post-randomization will be presented.
Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT)
The percentage of participants with a favorable clinical response at EOT will be presented.
Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU)
The percentage of participants with a favorable clinical response at EFU will be presented.
Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU)
The percentage of participants with a favorable clinical response at LFU will be presented.
Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT)
The percentage of participants with a favorable microbiological response at EOT will be presented.
Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU)
The percentage of participants with a favorable microbiological response at EFU will be presented.
Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU)
Percentage of participants with a favorable microbiological response at LFU will be presented.
Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Imipenem Following Administration of IMI/REL
Blood samples for AUC0-24 of imipenem analysis will be collected on Day 1 at 30 minutes prior to start of first dose of IV study intervention, within 10 minutes after the end of the first infusion, and 2 to 6 hours after the start of first infusion; and once at the on-therapy (OTX) visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day.
Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Relebactam Following Administration of IMI/REL
Blood samples for AUC0-24 of relebactam analysis will be collected on Day 1 at 30 minutes prior to start of first dose of IV study intervention, within 10 minutes after the end of the first infusion, and 2 to 6 hours after the start of first infusion; and once at the on-therapy (OTX) visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day.
Concentration at End of Infusion (Ceoi) of Imipenem Following Administration of IMI/REL
Blood samples for Ceoi of imipenem analysis will be collected within 10 minutes after the end of the first infusion on Day 1.
Concentration at End of Infusion (Ceoi) of Relabactam Following Administration of IMI/REL
Blood samples for Ceoi of relabactam analysis will be collected within 10 minutes after the end of the first infusion on Day 1.
Percentage of Time Imipenem Concentration Is Above Minimum Inhibitory Concentration (%T>MIC of Imipenem) Following Administration of IMI/REL
Blood samples for %T>MIC of imipenem analysis will be collected on Day 1 at 30 minutes prior to start of first dose of IV study intervention, within 10 minutes after the end of the first infusion, and 2 to 6 hours after the start of first infusion; and once at the on-therapy (OTX) visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day.

Full Information

First Posted
May 28, 2019
Last Updated
October 19, 2023
Sponsor
Merck Sharp & Dohme LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT03969901
Brief Title
Safety, Tolerability, Efficacy and Pharmacokinetics of Imipenem/Cilastatin/Relebactam (MK-7655A) in Pediatric Participants With Gram-negative Bacterial Infection (MK-7655A-021)
Official Title
A Phase 2/3 Open-label, Randomized, Active-controlled Clinical Study to Evaluate the Safety, Tolerability, Efficacy and Pharmacokinetics of MK-7655A in Pediatric Participants From Birth to Less Than 18 Years of Age With Confirmed or Suspected Gram-negative Bacterial Infection
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 8, 2019 (Actual)
Primary Completion Date
February 29, 2024 (Anticipated)
Study Completion Date
February 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Suspected or Documented Gram-negative Bacterial Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
IMI/REL
Arm Type
Experimental
Arm Description
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.
Arm Title
Active Control
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
IMI/REL
Other Intervention Name(s)
MK-7655A
Intervention Description
Age-based dosing: 12 to <18 years, IMI 500 and REL 250 mg, IV infusion every 6 hours 2 to <12 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 month, 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
Intervention Name(s)
Active Control
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With One or More Adverse Event (AE)
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants with AEs will be presented.
Time Frame
Up to 28 days
Title
Percentage of Participants Who Discontinued Study Medication Due to an Adverse Event (AE)
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study medication due to an AE will be presented.
Time Frame
Up to 14 days
Secondary Outcome Measure Information:
Title
Number of Deaths by All Causes Through Day 28
Description
All-cause mortality up to 28 days post-randomization will be presented.
Time Frame
Up to Day 28
Title
Percentage of Participants With a Favorable Clinical Response at End of Therapy (EOT)
Description
The percentage of participants with a favorable clinical response at EOT will be presented.
Time Frame
Day 5 up to Day 14
Title
Percentage of Participants With a Favorable Clinical Response at Early Follow-Up (EFU)
Description
The percentage of participants with a favorable clinical response at EFU will be presented.
Time Frame
Day 12 up to Day 28
Title
Percentage of Participants With a Favorable Clinical Response at Late Follow-Up (LFU)
Description
The percentage of participants with a favorable clinical response at LFU will be presented.
Time Frame
Day 19 up to Day 42
Title
Percentage of Participants With a Favorable Microbiological Response at End of Therapy (EOT)
Description
The percentage of participants with a favorable microbiological response at EOT will be presented.
Time Frame
Day 5 up to Day 14
Title
Percentage of Participants With a Favorable Microbiological Response at End of Follow-Up (EFU)
Description
The percentage of participants with a favorable microbiological response at EFU will be presented.
Time Frame
Day 12 up to Day 28
Title
Percentage of Participants With a Favorable Microbiological Response at Late Follow-Up (LFU)
Description
Percentage of participants with a favorable microbiological response at LFU will be presented.
Time Frame
Day 19 up to Day 42
Title
Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Imipenem Following Administration of IMI/REL
Description
Blood samples for AUC0-24 of imipenem analysis will be collected on Day 1 at 30 minutes prior to start of first dose of IV study intervention, within 10 minutes after the end of the first infusion, and 2 to 6 hours after the start of first infusion; and once at the on-therapy (OTX) visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day.
Time Frame
On Day 1 at 30 minutes prior to start of first IV infusion of study drug, at end of first infusion, and 2 to 6 hours after start of first infusion; and once at on-therapy visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day.
Title
Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of Relebactam Following Administration of IMI/REL
Description
Blood samples for AUC0-24 of relebactam analysis will be collected on Day 1 at 30 minutes prior to start of first dose of IV study intervention, within 10 minutes after the end of the first infusion, and 2 to 6 hours after the start of first infusion; and once at the on-therapy (OTX) visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day.
Time Frame
On Day 1 at 30 minutes prior to start of first IV infusion of study drug, at end of first infusion, and 2 to 6 hours after start of first infusion; and once at on-therapy visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day.
Title
Concentration at End of Infusion (Ceoi) of Imipenem Following Administration of IMI/REL
Description
Blood samples for Ceoi of imipenem analysis will be collected within 10 minutes after the end of the first infusion on Day 1.
Time Frame
At the end of the first infusion on Day 1.
Title
Concentration at End of Infusion (Ceoi) of Relabactam Following Administration of IMI/REL
Description
Blood samples for Ceoi of relabactam analysis will be collected within 10 minutes after the end of the first infusion on Day 1.
Time Frame
At the end of the first infusion on Day 1.
Title
Percentage of Time Imipenem Concentration Is Above Minimum Inhibitory Concentration (%T>MIC of Imipenem) Following Administration of IMI/REL
Description
Blood samples for %T>MIC of imipenem analysis will be collected on Day 1 at 30 minutes prior to start of first dose of IV study intervention, within 10 minutes after the end of the first infusion, and 2 to 6 hours after the start of first infusion; and once at the on-therapy (OTX) visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day.
Time Frame
On Day 1 at 30 minutes prior to start of first IV infusion of study drug, at end of first infusion, and 2 to 6 hours after start of first infusion; and once at on-therapy visit (Day 2 or Day 3) at 2 to 6 hours after start of any infusion that day.

10. Eligibility

Sex
All
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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/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 (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 (ie, 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 (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 for suspected meningitis prior to initiation of IV study intervention. If 3 months of age or older, or <3 months of age without suspected meningitis, 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Toll Free Number
Phone
1-888-577-8839
Email
Trialsites@merck.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Banner University Medical Center ( Site 0356)
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Individual Site Status
Completed
Facility Name
Miller Children's & Women's Hospital ( Site 0349)
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Individual Site Status
Completed
Facility Name
Rady Children's Hospital-San Diego ( Site 0347)
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
858-966-8381
Facility Name
Tufts Medical Center-Floating Hospital for Children ( Site 0350)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Individual Site Status
Completed
Facility Name
University of New Mexico ( Site 0358)
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Individual Site Status
Completed
Facility Name
University Hospital ( Site 0360)
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
210-567-5262
Facility Name
Children's Hospital of Richmond at VCU ( Site 0359)
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Individual Site Status
Completed
Facility Name
West Virginia University Ruby Memorial Hospital ( Site 0344)
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
304-293-1201
Facility Name
UMHAT Deva Maria. EOOD ( Site 0165)
City
Burgas
ZIP/Postal Code
8127
Country
Bulgaria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+35956896282
Facility Name
MHAT City Clinic Sv. Georgi EOOD ( Site 0167)
City
Montana
ZIP/Postal Code
3400
Country
Bulgaria
Individual Site Status
Completed
Facility Name
UMHAT Dr. Georgi Stranski EAD ( Site 0174)
City
Pleven
ZIP/Postal Code
5800
Country
Bulgaria
Individual Site Status
Completed
Facility Name
UMHAT Kanev AD ( Site 0168)
City
Ruse
ZIP/Postal Code
7002
Country
Bulgaria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+359899975275
Facility Name
UMHAT Kanev AD ( Site 0169)
City
Ruse
ZIP/Postal Code
7002
Country
Bulgaria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+359888209200
Facility Name
MHAT Dr. Ival Seliminski ( Site 0173)
City
Sliven
ZIP/Postal Code
8800
Country
Bulgaria
Individual Site Status
Completed
Facility Name
Hospital Roberto del Río ( Site 0802)
City
Santiago
State/Province
Region M. De Santiago
ZIP/Postal Code
8380418
Country
Chile
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
0992360000
Facility Name
Fundacion Hospital San Vicente de Paul ( Site 0269)
City
Medellin
State/Province
Antioquia
ZIP/Postal Code
050010
Country
Colombia
Individual Site Status
Completed
Facility Name
Clinica de la Costa S.A.S. ( Site 0264)
City
Barranquilla
State/Province
Atlantico
ZIP/Postal Code
080020
Country
Colombia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+573157609110
Facility Name
Sociedad de Cirugía de Bogotá - Hospital de San Jose ( Site 0265)
City
Bogota
State/Province
Distrito Capital De Bogota
ZIP/Postal Code
11001000
Country
Colombia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+573207532651
Facility Name
Fundacion Hospital Infantil Universitario de San Jose ( Site 0268)
City
Bogota
State/Province
Distrito Capital De Bogota
ZIP/Postal Code
111211
Country
Colombia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+573108059791
Facility Name
Fundacion Valle del Lili ( Site 0266)
City
Cali
State/Province
Valle Del Cauca
ZIP/Postal Code
760032
Country
Colombia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+573154896219
Facility Name
Tallinn Children Hospital ( Site 0209)
City
Tallinn
State/Province
Harjumaa
ZIP/Postal Code
13419
Country
Estonia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+37255573326
Facility Name
Hopitaux Pediatriques CHU Lenval ( Site 0143)
City
Nice
State/Province
Alpes-Maritimes
ZIP/Postal Code
06200
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+33492030579
Facility Name
Hopital Francois Mitterand ( Site 0146)
City
Dijon
State/Province
Cote-d Or
ZIP/Postal Code
21000
Country
France
Individual Site Status
Completed
Facility Name
Hopital Jeanne de Flandre ( Site 0145)
City
Lille
State/Province
Nord-Pas-de-Calais
ZIP/Postal Code
59120
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
33320446059
Facility Name
University of Athens - Aghia Sophia Childrens Hospital ( Site 0243)
City
Athens
State/Province
Attiki
ZIP/Postal Code
115 27
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+306974420425
Facility Name
Pan and Aglaia Kyriakou Children s Hospital ( Site 0247)
City
Athens
State/Province
Attiki
ZIP/Postal Code
11527
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+302107793000
Facility Name
Hippokration General Hospital of Thessaloniki ( Site 0244)
City
Thessaloniki
ZIP/Postal Code
546 42
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+302310892444
Facility Name
Debreceni Egyetem Klinikai Kozpont ( Site 0100)
City
Debrecen
State/Province
Hajdu-Bihar
ZIP/Postal Code
4032
Country
Hungary
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+36305769835
Facility Name
Szabolcs-Szatmar-Bereg Megyei Kórházak és Egyetemi Otatókórház-Gyermekosztály ( Site 0105)
City
Nyiregyhaza
State/Province
Szabolcs-Szatmar-Bereg
ZIP/Postal Code
4400
Country
Hungary
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+36302565180
Facility Name
Rambam Medical Center ( Site 0189)
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+97247774810
Facility Name
Hadassah Ein Karem Hebrew University Medical Center ( Site 0188)
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+97226777111
Facility Name
Schneider Children's Medical Center ( Site 0187)
City
Petah Tikva
ZIP/Postal Code
4920235
Country
Israel
Individual Site Status
Completed
Facility Name
Chaim Sheba Medical Center ( Site 0190)
City
Ramat Gan
ZIP/Postal Code
5262100
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+97235305978
Facility Name
Hospital General de Tijuana ( Site 0284)
City
Tijuana
State/Province
Baja California
ZIP/Postal Code
22000
Country
Mexico
Individual Site Status
Completed
Facility Name
Hospital del Nino y Adolescente Morelense ( Site 0286)
City
Emiliano Zapata
State/Province
Morelos
ZIP/Postal Code
62765
Country
Mexico
Individual Site Status
Completed
Facility Name
Centenario Hospital Miguel Hidalgo-Pediatrics Department ( Site 0290)
City
Aguascalientes
ZIP/Postal Code
20259
Country
Mexico
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+524499946720
Facility Name
Instituto Nacional de Pediatria ( Site 0291)
City
Ciudad de Mexico
ZIP/Postal Code
04530
Country
Mexico
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+525510840900
Facility Name
Haukeland Universitetssjukehus ( Site 0500)
City
Bergen
State/Province
Hordaland
ZIP/Postal Code
5021
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+4755975720
Facility Name
University of the Philippines-Philippine General Hospital ( Site 0318)
City
Manila
State/Province
National Capital Region
ZIP/Postal Code
1000
Country
Philippines
Individual Site Status
Completed
Facility Name
Philippine Children s Medical Center ( Site 0317)
City
Quezon City
State/Province
National Capital Region
ZIP/Postal Code
1104
Country
Philippines
Individual Site Status
Completed
Facility Name
Wojewodzki Szpital Zespolony im. Rydgiera ( Site 0220)
City
Torun
State/Province
Kujawsko-pomorskie
ZIP/Postal Code
87-100
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+48566794601
Facility Name
Instytut Centrum Zdrowia Matki Polki ( Site 0223)
City
Lodz
State/Province
Lodzkie
ZIP/Postal Code
93-338
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+48422711391
Facility Name
SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 0226)
City
Lomianki
State/Province
Mazowieckie
ZIP/Postal Code
05-092
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+48227657153
Facility Name
Pediatric Hematology Oncology and Immunology Centre n.a. D.Rogachev. ( Site 0233)
City
Moscow
State/Province
Moskva
ZIP/Postal Code
117197
Country
Russian Federation
Individual Site Status
Completed
Facility Name
Morozovskaya Children City Clinical Hospital ( Site 0241)
City
Moscow
State/Province
Moskva
ZIP/Postal Code
119049
Country
Russian Federation
Individual Site Status
Suspended
Facility Name
State Budgetary Healthcare Institution of Novosibirsk Region City Childrens Clinical Emergency Hospi
City
Novosibirsk
State/Province
Novosibirskaya Oblast
ZIP/Postal Code
630011
Country
Russian Federation
Individual Site Status
Suspended
Facility Name
St.Petersburg State Pediatric Medical University ( Site 0236)
City
Saint Petersburg
State/Province
Sankt-Peterburg
ZIP/Postal Code
194100
Country
Russian Federation
Individual Site Status
Completed
Facility Name
Children's City Clinical Hospital #1 ( Site 0237)
City
Saint Petersburg
State/Province
Sankt-Peterburg
ZIP/Postal Code
198205
Country
Russian Federation
Individual Site Status
Completed
Facility Name
Children s City Clinical Hospital 5 n.a. N.F. Filatov ( Site 0235)
City
St. Petersburg
State/Province
Sankt-Peterburg
ZIP/Postal Code
192289
Country
Russian Federation
Individual Site Status
Suspended
Facility Name
Smolensk Regional Clinical Hospital ( Site 0231)
City
Smolensk
State/Province
Smolenskaya Oblast
ZIP/Postal Code
214018
Country
Russian Federation
Individual Site Status
Suspended
Facility Name
Regional Childrens Clinical Hospital ( Site 0400)
City
Vologda
State/Province
Vologodskaya Oblast
ZIP/Postal Code
160022
Country
Russian Federation
Individual Site Status
Completed
Facility Name
Empilweni Services and Research Unit ( Site 1557)
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2001
Country
South Africa
Individual Site Status
Completed
Facility Name
Chris Hani Baragwanath Academic Hospital ( Site 0156)
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2013
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+27119330270
Facility Name
Molotlegi Street ( Site 0155)
City
Pretoria
State/Province
Gauteng
ZIP/Postal Code
0208
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+27125215633
Facility Name
Hospital Infantil Universitario Nino Jesus ( Site 0114)
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+34915035900
Facility Name
Hospital Universitario La Paz ( Site 0113)
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Completed
Facility Name
Hospital Universitario Virgen del Rocio ( Site 0115)
City
Sevilla
ZIP/Postal Code
41043
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
34955013767
Facility Name
Cukurova University Medical Faculty ( Site 0200)
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+905326534166
Facility Name
Ankara Universitesi Tip Fakultesi. ( Site 0202)
City
Ankara
ZIP/Postal Code
06590
Country
Turkey
Individual Site Status
Active, not recruiting
Facility Name
Eskisehir Osmangazi University Medical ( Site 0201)
City
Eskisehir
ZIP/Postal Code
26480
Country
Turkey
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+905339243269
Facility Name
SBU Sariyer Hamidiye Etfal Egitim ve Arastirma Hastanesi ( Site 0198)
City
Istanbul
ZIP/Postal Code
34453
Country
Turkey
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+905055803297
Facility Name
Ege Universitesi Tıp Fakultesi Hastanesi ( Site 0199)
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Individual Site Status
Completed
Facility Name
SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 0121)
City
Dnipro
State/Province
Dnipropetrovska Oblast
ZIP/Postal Code
49100
Country
Ukraine
Individual Site Status
Suspended
Facility Name
PI Kryvorizka city clinical hospital 8 of Dnipropetrovsk Reg Council ( Site 0128)
City
Kryvyy Rig
State/Province
Dnipropetrovska Oblast
ZIP/Postal Code
50082
Country
Ukraine
Individual Site Status
Suspended
Facility Name
Ivano-Frankivsk Regional Children Clinical Hospital ( Site 0131)
City
Ivano-Frankivsk
State/Province
Ivano-Frankivska Oblast
ZIP/Postal Code
76014
Country
Ukraine
Individual Site Status
Suspended
Facility Name
Kharkiv City Children Hospital 16 ( Site 0130)
City
Kharkiv
State/Province
Kharkivska Oblast
ZIP/Postal Code
61075
Country
Ukraine
Individual Site Status
Suspended
Facility Name
Municipal Enterprise Children's City Clinical Hospital in Poltava City Council ( Site 0122)
City
Poltava
State/Province
Poltavska Oblast
ZIP/Postal Code
36004
Country
Ukraine
Individual Site Status
Suspended

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
https://www.merckclinicaltrials.com/
Description
Merck Clinical Trials Information

Learn more about this trial

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

We'll reach out to this number within 24 hrs