Clinical trial NCT03217136: MK-7625A Plus Metronidazole Versus Meropenem in Pediatric Participants With Complicated Intra-Abdominal Infection (cIAI) (MK-7625A-035)
Official title: A Phase 2, Randomized, Active Comparator-Controlled, Multicenter, Double-Blind Clinical Trial to Study the Safety and Efficacy of Ceftolozane/Tazobactam (MK-7625A) Plus Metronidazole Versus Meropenem in Pediatric Subjects With Complicated Intra-Abdominal Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Complicated Intra-Abdominal Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-07-13
Enrollment: 94
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants Experiencing ≥1 Adverse Events (AEs)
timeFrame: Up to approximately 75 days
measure: Number of Participants Who Discontinued Study Therapy Due to AE(s)
timeFrame: Up to approximately 18 days
Secondary outcomes:
measure: Percentage of Participants With a Clinical Response of "Cure" at the End of Treatment (EOT) Visit
timeFrame: Up to approximately 27 days
measure: Percentage of Participants With a Clinical Response of "Cure" at the Test of Cure (TOC) Visit
timeFrame: Up to approximately 39 days
measure: Percentage of Participants With Microbiological Eradication at the EOT Visit
timeFrame: Up to approximately 27 days
measure: Percentage of Participants With Microbiological Eradication at the TOC Visit
timeFrame: Up to approximately 39 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital - Los Angeles ( Site 2508)
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County ( Site 2502)
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital-San Diego ( Site 2505)
state: California
city: Jacksonville
country: United States
facility: Baptist Medical Center/Wolfson Children's Hospital ( Site 2521)
state: Florida
city: Boston
country: United States
facility: Tufts Medical Center-Floating Hospital for Children ( Site 2516)
state: Massachusetts
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital ( Site 2511)
state: Missouri
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital ( Site 2509)
state: New York
city: Salt Lake City
country: United States
facility: Primary Children's Hospital ( Site 2500)
state: Utah
city: Seattle
country: United States
facility: Seattle Childrens Hospital ( Site 2510)
state: Washington
city: Curitiba
country: Brazil
facility: Hospital Pequeno Principe ( Site 0200)
state: Parana
city: Recife
country: Brazil
facility: Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0201)
state: Pernambuco
city: Bento Goncalves
country: Brazil
facility: Hospital Tacchini ( Site 0203)
state: Rio Grande Do Sul
city: Pecs
country: Hungary
facility: PTE AOK Klinikai Kozpont ( Site 0805)
state: Baranya
city: Nyiregyhaza
country: Hungary
facility: SzSzBMK es Egyetemi Oktatokorhaz Josa Andras Oktatokorhaz ( Site 0804)
state: Szabolcs-Szatmar-Bereg
city: Budapest
country: Hungary
facility: Semmelweis Egyetem ( Site 0807)
city: Budapest
country: Hungary
facility: Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0806)
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont ( Site 0801)
city: Szeged
country: Hungary
facility: SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0802)
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas ( Site 1001)
city: Klaipeda
country: Lithuania
facility: Klaipedos Vaiku Ligonine ( Site 1000)
city: Vilnius
country: Lithuania
facility: Vaiku Ligonine VU ligonines Santariskiu kliniku filialas ( Site 1002)
city: Cheras
country: Malaysia
facility: Universiti Kebangsaan Malaya Medical Centre ( Site 1101)
state: Johor
city: Georgetown
country: Malaysia
facility: Hospital Pulau Pinang ( Site 1102)
state: Pulau Pinang
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre. ( Site 1100)
city: Emiliano Zapata
country: Mexico
facility: Hospital del Nino y Adolescente Morelense ( Site 1204)
state: Morelos
city: Monterrey
country: Mexico
facility: Instituto Tecnologico y de Estudios Superiores de Monterrey ( Site 1203)
state: Nuevo Leon
city: Mexico City
country: Mexico
facility: Instituto Nacional de Pediatria ( Site 1201)
city: Mexico City
country: Mexico
facility: Hospital Infantil de Mexico Federico Gomez ( Site 1202)
city: Cluj-Napoca
country: Romania
facility: Spit. Cl. de Urg. Copii Cluj Napoca ( Site 1703)
state: Cluj
city: Timisoara
country: Romania
facility: Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu" Timi ( Site 1701)
state: Timis
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Children Clinical Hospital ( Site 1802)
state: Chelyabinskaya Oblast
city: Smolensk
country: Russian Federation
facility: Smolensk Regional Clinical Hospital ( Site 1800)
state: Smolenskaya Oblast
city: Stavropol
country: Russian Federation
facility: Stavropol Regional Pediatric Clinical Hospital ( Site 1805)
state: Stavropol Skiy Kray
city: Vologda
country: Russian Federation
facility: Regional Childrens Clinical Hospital ( Site 1809)
state: Vologodskaya Oblast
city: Pretoria
country: South Africa
facility: Molotlegi Street ( Site 1901)
state: Gauteng
city: Cape Town
country: South Africa
facility: Red Cross War Memorial Children's Hospital ( Site 1902)
state: Western Cape
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago ( Site 2001)
state: A Coruña [La Coruña]
city: Badalona
country: Spain
facility: Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 2004)
state: Barcelona
city: Esplugues de Llobregat
country: Spain
facility: Hospital Universitario Sant Joan de Deu ( Site 2000)
state: Barcelona
city: Valencia
country: Spain
facility: Hospital Universitario la Fe ( Site 2003)
state: Valenciana, Comunitat
city: Adana
country: Turkey
facility: Cukurova Uni Tip Fak Cocuk Saglıgı ve Hasta ABD ( Site 2200)
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2201)
city: Eskisehir
country: Turkey
facility: Eskisehir Osmangazi Unv. Tip Fakultesi ( Site 2202)
city: Istanbul
country: Turkey
facility: SBU Sariyer Hamidiye Etfal Egitim ve Arastirma Hastanesi ( Site 2203)
city: Dnipro
country: Ukraine
facility: SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 2452)
state: Dnipropetrovska Oblast
city: Kryvyy Rig
country: Ukraine
facility: PI Kryvorizka city clinical hospital 8 ( Site 2458)
state: Dnipropetrovska Oblast
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Children Clinical Hospital ( Site 2461)
state: Ivano-Frankivska Oblast
city: Kyiv
country: Ukraine
facility: National Children Specialised Hospital OHMADYT MOH Ukraine ( Site 2459)
state: Kyivska Oblast
city: Poltava
country: Ukraine
facility: Municipal Institution City Children s Clinical Hospital of Poltava City Council ( Site 2454)
state: Poltavska Oblast
city: Vinnytsya
country: Ukraine
facility: Vinnytsya Regional Children Clinical Hospital ( Site 2463)
state: Vinnytska Oblast
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.