MK-7625A Plus Metronidazole Versus Meropenem in Pediatric Participants With Complicated Intra-Abdominal Infection (cIAI) (MK-7625A-035)

NCT ID: NCT03217136

Last Updated: 2023-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-03
• Study Completion Date: 2020-03-16

Brief Summary

This study aims to evaluate the safety and tolerability of MK-7625A (ceftolozane/tazobactam) plus metronidazole, compared with that of meropenem in pediatric participants with cIAI.

Conditions

Complicated Intra-Abdominal Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ceftolozane/Tazobactam + Metronidazole

Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.

Group Type: EXPERIMENTAL

Ceftolozane/Tazobactam

Intervention Type: DRUG

Ceftolozane 20 mg/kg (maximum 1 g) and tazobactam 10 mg/kg (maximum 0.5 g/dose) administered IV every 8 hours for between 5 to 14 days.

Metronidazole

Intervention Type: DRUG

Metronidazole 10 mg/kg (maximum 1.5 g/day) administered IV every 8 hours for between 5 to 14 days. Participants ≤ 28 days old, start with a loading dose of 15 mg/kg; then if ≤ 2 kg are dosed 7.5 mg/kg/ every 12 hours; or if \> 2 kg are dosed 10 mg/kg every 8 hours.

Meropenem + Placebo for Metronidazole

Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for Metronidazole administered IV every 8 hours for 5 to 14 days.

Group Type: ACTIVE_COMPARATOR

Meropenem

Intervention Type: DRUG

Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for between 5 to 14 days.

Placebo for Metronidazole

Intervention Type: DRUG

Placebo for metronidazole administered IV every 8 hours for between 5 to 14 days.

Interventions

Ceftolozane/Tazobactam

Ceftolozane 20 mg/kg (maximum 1 g) and tazobactam 10 mg/kg (maximum 0.5 g/dose) administered IV every 8 hours for between 5 to 14 days.

Intervention Type: DRUG

Metronidazole

Metronidazole 10 mg/kg (maximum 1.5 g/day) administered IV every 8 hours for between 5 to 14 days. Participants ≤ 28 days old, start with a loading dose of 15 mg/kg; then if ≤ 2 kg are dosed 7.5 mg/kg/ every 12 hours; or if \> 2 kg are dosed 10 mg/kg every 8 hours.

Intervention Type: DRUG

Meropenem

Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for between 5 to 14 days.

Intervention Type: DRUG

Placebo for Metronidazole

Placebo for metronidazole administered IV every 8 hours for between 5 to 14 days.

Intervention Type: DRUG

Other Intervention Names

MK-7625A; MERREM

Eligibility Criteria

Inclusion Criteria

• Has a legally acceptable representative who provides documented informed consent/assent for the trial.
• Aged from birth (defined as >32 weeks gestational age and ≥7 days postnatal) to <18 years of age.
• Require IV antibacterial therapy for the treatment of presumed or documented cIAI.
• Has an operative procedure for the current diagnosis and management of cIAI planned or completed within 24 hours of the first dose of an antibacterial drug. Note: Participants with a diagnosis of necrotizing enterocolitis are exempt and not required to have surgery planned or completed in order to be eligible.
• Has in compliance baseline intra-abdominal specimen collection.
• Is not of reproductive potential; but if of reproductive potential agrees to avoid becoming pregnant or impregnating a partner during screening, while receiving study treatment and for at least 30 days after the last dose of study treatment.
• Female of reproductive potential is not pregnant, and not planning to become pregnant within 30 days of the last day of treatment administration; and is nonlactating.

Exclusion Criteria

• Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days prior to the first dose of study treatment in this current trial.
• Has previously participated in any trial of ceftolozane or ceftolozane/tazobactam or has enrolled previously in the current trial and been discontinued.
• Has a history of any moderate or severe hypersensitivity (e.g, anaphylaxis), allergic reaction, or other contraindication to any of the following: β-lactam antibiotics (e.g, penicillins, cephalosporins, and carbapenems), β-lactamase inhibitors (e.g, tazobactam, sulbactam, clavulanic acid, avibactam), or metronidazole.
• Has an IAI within the past 1 year prior to randomization known to be caused by a pathogen resistant to either IV study treatment.
• Has a 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 received potentially therapeutic antibacterial therapy for a duration more than 24 hours during the 48 hours preceding the first dose of study treatment, unless is considered to be failing antibiotic therapy for cIAI.
• Has any of the following: a) intractable cIAI that the investigator anticipates would require more than 14 days of study treatment; b) abdominal wall abscess; c) small bowel obstruction; d) ischemic bowel disease without perforation; e) traumatic bowel perforation with surgery within 12 hours of perforation; f) perforation of gastroduodenal ulcers requiring surgery within 24 hours of perforation; g) suspected uncomplicated intra-abdominal infection (e.g, cholecystitis without rupture or extension beyond the gallbladder wall); h) acute suppurative cholangitis; i) infected necrotizing pancreatitis; j) pancreatic abscess.
• Has moderate or severe impairment of renal function.
• Has a seizure disorder or is anticipated to be treated with divalproex sodium or valproic acid during the course of study treatment.
• Is receiving, or is expected to receive, any prohibited medications.
• Has any rapidly progressing disease or immediately life-threatening illness, including acute hepatic failure, respiratory failure, or septic shock.
• Has an immunocompromising condition.
• Has a history of malignancy ≤5 years prior to signing informed consent.
• Is planning to receive suppressive/prophylactic antibiotics with gram-negative activity after completion of study treatment.

• Minimum Eligible Age: 7 Days
• 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

Children's Hospital - Los Angeles ( Site 2508)

Los Angeles, California, United States

Children's Hospital of Orange County ( Site 2502)

Orange, California, United States

Rady Children's Hospital-San Diego ( Site 2505)

San Diego, California, United States

Baptist Medical Center/Wolfson Children's Hospital ( Site 2521)

Jacksonville, Florida, United States

Tufts Medical Center-Floating Hospital for Children ( Site 2516)

Boston, Massachusetts, United States

St. Louis Children's Hospital ( Site 2511)

St Louis, Missouri, United States

SUNY Upstate Medical University Hospital ( Site 2509)

Syracuse, New York, United States

Primary Children's Hospital ( Site 2500)

Salt Lake City, Utah, United States

Seattle Childrens Hospital ( Site 2510)

Seattle, Washington, United States

Hospital Pequeno Principe ( Site 0200)

Curitiba, Paraná, Brazil

Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0201)

Recife, Pernambuco, Brazil

Hospital Tacchini ( Site 0203)

Bento Gonçalves, Rio Grande do Sul, Brazil

PTE AOK Klinikai Kozpont ( Site 0805)

Pécs, Baranya, Hungary

SzSzBMK es Egyetemi Oktatokorhaz Josa Andras Oktatokorhaz ( Site 0804)

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

Semmelweis Egyetem ( Site 0807)

Budapest, , Hungary

Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0806)

Budapest, , Hungary

Debreceni Egyetem Klinikai Kozpont ( Site 0801)

Debrecen, , Hungary

SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0802)

Szeged, , Hungary

Hospital of Lithuanian University of Health Sciences Kaunas ( Site 1001)

Kaunas, , Lithuania

Klaipedos Vaiku Ligonine ( Site 1000)

Klaipėda, , Lithuania

Vaiku Ligonine VU ligonines Santariskiu kliniku filialas ( Site 1002)

Vilnius, , Lithuania

Universiti Kebangsaan Malaya Medical Centre ( Site 1101)

Cheras, Johor, Malaysia

Hospital Pulau Pinang ( Site 1102)

George Town, Pulau Pinang, Malaysia

University Malaya Medical Centre. ( Site 1100)

Kuala Lumpur, , Malaysia

Hospital del Nino y Adolescente Morelense ( Site 1204)

Emiliano Zapata, Morelos, Mexico

Instituto Tecnologico y de Estudios Superiores de Monterrey ( Site 1203)

Monterrey, Nuevo León, Mexico

Instituto Nacional de Pediatria ( Site 1201)

Mexico City, , Mexico

Hospital Infantil de Mexico Federico Gomez ( Site 1202)

Mexico City, , Mexico

Spit. Cl. de Urg. Copii Cluj Napoca ( Site 1703)

Cluj-Napoca, Cluj, Romania

Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu" Timi ( Site 1701)

Timișoara, Timiș County, Romania

Chelyabinsk Regional Children Clinical Hospital ( Site 1802)

Chelyabinsk, Chelyabinsk Oblast, Russia

Smolensk Regional Clinical Hospital ( Site 1800)

Smolensk, Smolensk Oblast, Russia

Stavropol Regional Pediatric Clinical Hospital ( Site 1805)

Stavropol, Stavropol Kray, Russia

Regional Childrens Clinical Hospital ( Site 1809)

Vologda, Vologda Oblast, Russia

Molotlegi Street ( Site 1901)

Pretoria, Gauteng, South Africa

Red Cross War Memorial Children's Hospital ( Site 1902)

Cape Town, Western Cape, South Africa

Hospital Clinico Universitario de Santiago ( Site 2001)

Santiago de Compostela, A Coruña [La Coruña], Spain

Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 2004)

Badalona, Barcelona, Spain

Hospital Universitario Sant Joan de Deu ( Site 2000)

Esplugues de Llobregat, Barcelona, Spain

Hospital Universitario la Fe ( Site 2003)

Valencia, Valenciana, Comunitat, Spain

Cukurova Uni Tip Fak Cocuk Saglıgı ve Hasta ABD ( Site 2200)

Adana, , Turkey (Türkiye)

Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2201)

Ankara, , Turkey (Türkiye)

Eskisehir Osmangazi Unv. Tip Fakultesi ( Site 2202)

Eskişehir, , Turkey (Türkiye)

SBU Sariyer Hamidiye Etfal Egitim ve Arastirma Hastanesi ( Site 2203)

Istanbul, , Turkey (Türkiye)

SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 2452)

Dnipro, Dnipropetrovsk Oblast, Ukraine

PI Kryvorizka city clinical hospital 8 ( Site 2458)

Kryvyy Rig, Dnipropetrovsk Oblast, Ukraine

Ivano-Frankivsk Regional Children Clinical Hospital ( Site 2461)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

National Children Specialised Hospital OHMADYT MOH Ukraine ( Site 2459)

Kyiv, Kyivska Oblast, Ukraine

Municipal Institution City Children s Clinical Hospital of Poltava City Council ( Site 2454)

Poltava, Poltava Oblast, Ukraine

Vinnytsya Regional Children Clinical Hospital ( Site 2463)

Vinnytsia, Vinnytsia Oblast, Ukraine

Countries

United States; Brazil; Hungary; Lithuania; Malaysia; Mexico; Romania; Russia; South Africa; Spain; Turkey (Türkiye); Ukraine

References

Jackson CA, Newland J, Dementieva N, Lonchar J, Su FH, Huntington JA, Bensaci M, Popejoy MW, Johnson MG, De Anda C, Rhee EG, Bruno CJ. Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection. Pediatr Infect Dis J. 2023 Jul 1;42(7):557-563. doi: 10.1097/INF.0000000000003911. Epub 2023 Mar 29.

Reference Type: RESULT

PMID: 37000942 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-7625A-035

Identifier Type: OTHER

Identifier Source: secondary_id

2016-004820-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

7625A-035

Identifier Type: -

Identifier Source: org_study_id