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

Complicated Intra-Abdominal Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03217136
• Other study ID #: 7625A-035
• Secondary ID: MK-7625A-0352016
• Status: Completed
• Phase: Phase 2
• Start date: April 3, 2018
• Est. completion date: March 16, 2020

Study information

• Verified date: May 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: March 16, 2020
• Est. primary completion date: March 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Days to 17 Years

Eligibility

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: ß-lactam antibiotics (e.g, penicillins, cephalosporins, and carbapenems), ß-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.

Related Conditions & MeSH terms

• Communicable Diseases
• Complicated Intra-Abdominal Infection
• Infections
• Intraabdominal Infections

Intervention

Drug:
• 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.
• 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.
• Meropenem
Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for between 5 to 14 days.
• Placebo for Metronidazole
Placebo for metronidazole administered IV every 8 hours for between 5 to 14 days.

Locations

Country	Name	City	State
Brazil	Hospital Tacchini ( Site 0203)	Bento Goncalves	Rio Grande Do Sul
Brazil	Hospital Pequeno Principe ( Site 0200)	Curitiba	Parana
Brazil	Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0201)	Recife	Pernambuco
Hungary	Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0806)	Budapest
Hungary	Semmelweis Egyetem ( Site 0807)	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont ( Site 0801)	Debrecen
Hungary	SzSzBMK es Egyetemi Oktatokorhaz Josa Andras Oktatokorhaz ( Site 0804)	Nyiregyhaza	Szabolcs-Szatmar-Bereg
Hungary	PTE AOK Klinikai Kozpont ( Site 0805)	Pecs	Baranya
Hungary	SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0802)	Szeged
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas ( Site 1001)	Kaunas
Lithuania	Klaipedos Vaiku Ligonine ( Site 1000)	Klaipeda
Lithuania	Vaiku Ligonine VU ligonines Santariskiu kliniku filialas ( Site 1002)	Vilnius
Malaysia	Universiti Kebangsaan Malaya Medical Centre ( Site 1101)	Cheras	Johor
Malaysia	Hospital Pulau Pinang ( Site 1102)	Georgetown	Pulau Pinang
Malaysia	University Malaya Medical Centre. ( Site 1100)	Kuala Lumpur
Mexico	Hospital del Nino y Adolescente Morelense ( Site 1204)	Emiliano Zapata	Morelos
Mexico	Hospital Infantil de Mexico Federico Gomez ( Site 1202)	Mexico City
Mexico	Instituto Nacional de Pediatria ( Site 1201)	Mexico City
Mexico	Instituto Tecnologico y de Estudios Superiores de Monterrey ( Site 1203)	Monterrey	Nuevo Leon
Romania	Spit. Cl. de Urg. Copii Cluj Napoca ( Site 1703)	Cluj-Napoca	Cluj
Romania	Spitalul Clinic de Urgenta pentru Copii "Louis Turcanu" Timi ( Site 1701)	Timisoara	Timis
Russian Federation	Chelyabinsk Regional Children Clinical Hospital ( Site 1802)	Chelyabinsk	Chelyabinskaya Oblast
Russian Federation	Smolensk Regional Clinical Hospital ( Site 1800)	Smolensk	Smolenskaya Oblast
Russian Federation	Stavropol Regional Pediatric Clinical Hospital ( Site 1805)	Stavropol	Stavropol Skiy Kray
Russian Federation	Regional Childrens Clinical Hospital ( Site 1809)	Vologda	Vologodskaya Oblast
South Africa	Red Cross War Memorial Children's Hospital ( Site 1902)	Cape Town	Western Cape
South Africa	Molotlegi Street ( Site 1901)	Pretoria	Gauteng
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 Clinico Universitario de Santiago ( Site 2001)	Santiago de Compostela	A Coruña [La Coruña]
Spain	Hospital Universitario la Fe ( Site 2003)	Valencia	Valenciana, Comunitat
Turkey	Cukurova Uni Tip Fak Cocuk Sagligi ve Hasta ABD ( Site 2200)	Adana
Turkey	Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2201)	Ankara
Turkey	Eskisehir Osmangazi Unv. Tip Fakultesi ( Site 2202)	Eskisehir
Turkey	SBU Sariyer Hamidiye Etfal Egitim ve Arastirma Hastanesi ( Site 2203)	Istanbul
Ukraine	SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 2452)	Dnipro	Dnipropetrovska Oblast
Ukraine	Ivano-Frankivsk Regional Children Clinical Hospital ( Site 2461)	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	PI Kryvorizka city clinical hospital 8 ( Site 2458)	Kryvyy Rig	Dnipropetrovska 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	Poltavska Oblast
Ukraine	Vinnytsya Regional Children Clinical Hospital ( Site 2463)	Vinnytsya	Vinnytska Oblast
United States	Tufts Medical Center-Floating Hospital for Children ( Site 2516)	Boston	Massachusetts
United States	Baptist Medical Center/Wolfson Children's Hospital ( Site 2521)	Jacksonville	Florida
United States	Children's Hospital - Los Angeles ( Site 2508)	Los Angeles	California
United States	Children's Hospital of Orange County ( Site 2502)	Orange	California
United States	St. Louis Children's Hospital ( Site 2511)	Saint Louis	Missouri
United States	Primary Children's Hospital ( Site 2500)	Salt Lake City	Utah
United States	Rady Children's Hospital-San Diego ( Site 2505)	San Diego	California
United States	Seattle Childrens Hospital ( Site 2510)	Seattle	Washington
United States	SUNY Upstate Medical University Hospital ( Site 2509)	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Brazil,  Hungary,  Lithuania,  Malaysia,  Mexico,  Romania,  Russian Federation,  South Africa,  Spain,  Turkey,  Ukraine, 

References & Publications (1)

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 Tr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing =1 Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented.	Up to approximately 75 days
Primary	Number of Participants Who Discontinued Study Therapy Due to AE(s)	An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented.	Up to approximately 18 days
Secondary	Percentage of Participants With a Clinical Response of "Cure" at the End of Treatment (EOT) Visit	The percentage of participants who had a clinical outcome of "cure" at the time of the EOT visit is presented. The "cure" clinical outcome was defined as complete resolution or marked improvement in signs and symptoms of the complicated intra-abdominal infection (cIAI) or return to pre-infection signs and symptoms such that no further antibiotic therapy (intravenous or oral) or surgical or drainage procedure is required for treatment of the cIAI. Participants who were missing clinical response data were considered treatment failures.	Up to approximately 27 days
Secondary	Percentage of Participants With a Clinical Response of "Cure" at the Test of Cure (TOC) Visit	The percentage of participants who had a clinical outcome of "cure" at the time of the TOC visit is presented. The "cure" clinical outcome was defined as complete resolution or marked improvement in signs and symptoms of the complicated intra-abdominal infection (cIAI) or return to pre-infection signs and symptoms such that no further antibiotic therapy (intravenous or oral) or surgical or drainage procedure is required for treatment of the cIAI. Participants who were missing clinical response data were considered treatment failures.	Up to approximately 39 days
Secondary	Percentage of Participants With Microbiological Eradication at the EOT Visit	The percentage of participants who achieved either eradication or presumed eradication of each baseline infecting pathogen by the time of the EOT visit is presented. Eradication was defined as absence of the baseline pathogen(s) in a postbaseline specimen appropriately obtained from the original site of infection. Presumed eradication was defined as absence of material to culture in a participant who is assessed as having partial improvement, or clinical cure. In the event of multiple baseline pathogens, the least favorable microbiological response from all possible baseline pathogens was used.	Up to approximately 27 days
Secondary	Percentage of Participants With Microbiological Eradication at the TOC Visit	The percentage of participants who achieved either eradication or presumed eradication of each baseline infecting pathogen by the time of the TOC visit is presented. Eradication was defined as absence of the baseline pathogen(s) in a postbaseline specimen appropriately obtained from the original site of infection. Presumed eradication was defined as absence of material to culture in a participant who is assessed as having partial improvement, or clinical cure. In the event of multiple baseline pathogens, the least favorable microbiological response from all possible baseline pathogens was used.	Up to approximately 39 days