MK-7625A Versus Meropenem in Pediatric Participants With Complicated Urinary Tract Infection (cUTI) (MK-7625A-034)

A Phase 2, Randomized, Active Comparator-Controlled, Multicenter, Double-Blind Clinical Trial to Study the Safety and Efficacy of Ceftolozane/Tazobactam (MK-7625A) Versus Meropenem in Pediatric Subjects With Complicated Urinary Tract Infection, Including Pyelonephritis

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

Study Overview

• Status: Completed
• Conditions: Pyelonephritis; Complicated Urinary Tract Infection
• Intervention / Treatment: Drug: Ceftolozane/Tazobactam; Drug: Meropenem

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Attiki
    • Athens, Attiki, Greece, 115 27
      • Pan and Aglaia Kyriakou Children s Hospital ( Site 0780)
    • Athens, Attiki, Greece, 115 27
      • University of Athens - Aghia Sophia Childrens Hospital ( Site 0730)
    • Athens, Attiki, Greece, 124 62
      • Athens University Hospital ATTIKON ( Site 0790)
  • Thessalia
    • Larissa, Thessalia, Greece, 411 10
      • General University Hospital of Larissa ( Site 0740)
  • Thessaloníki
    • Thessaloniki, Thessaloníki, Greece, 546 42
      • Hippokration General Hospital of Thessaloniki ( Site 0700)
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem ( Site 0810)
  • Budapest, Hungary, 1089
    • Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0801)
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont ( Site 0803)
  • Baranya
    • Pecs, Baranya, Hungary, 7623
      • PTE AOK Klinikai Kozpont ( Site 0809)
  • Csongrad
    • Szeged, Csongrad, Hungary, 6720
      • SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0804)
  • Szabolcs-Szatmar-Bereg
    • Nyiregyhaza, Szabolcs-Szatmar-Bereg, Hungary, 4400
      • SzSzBMK es Egyetemi Oktatokorhaz Josa Andras Oktatokorhaz ( Site 0808)
• Mexico
  • Mexico City, Mexico, 04530
    • Instituto Nacional de Pediatria ( Site 1201)
  • Mexico City, Mexico, 06720
    • Hospital Infantil de Mexico Federico Gomez ( Site 1203)
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 1202)
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64710
      • Instituto Tecnologico y de Estudios Superiores de Monterrey ( Site 1204)
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-030
      • Wojewodzki Szpital Obserwacyjno Zakazny ( Site 1606)
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-094
      • Szpital Uniwersytecki nr 1 im. Dr. Antoniego Jurasza w Bydgoszczy ( Site 1600)
    • Torun, Kujawsko-pomorskie, Poland, 87-100
      • Wojewodzki Szpital Zespolony im. Rydgiera ( Site 1607)
  • Lodzkie
    • Lodz, Lodzkie, Poland, 93-338
      • Instytut Centrum Zdrowia Matki Polki ( Site 1602)
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-663
      • Uniw. Szpital Dzieciecy w Krakowie ( Site 1609)
  • Mazowieckie
    • Lomianki, Mazowieckie, Poland, 05-092
      • SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 1608)
• Romania
  • Brasov, Romania, 500063
    • Spitalul Clinic de Urgenta pentru Copii Brasov ( Site 1703)
  • Bucuresti, Romania, 021106
    • Institutul National de Boli Infectioase Prof. Dr. Matei Bals ( Site 1706)
  • Bucuresti
    • Bucharest, Bucuresti, Romania, 041451
      • Spitalul Clinic de Urgenta pentru Copii Maria Sklodowska Curie ( Site 1707)
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400177
      • Spit. Cl. de Urg. Copii Cluj Napoca ( Site 1708)
• Russian Federation
  • Moskva
    • Moscow, Moskva, Russian Federation, 119571
      • Russian Pediatric Clinical Hospital ( Site 1808)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 194100
      • St.Petersburg State Pediatric Medical University ( Site 1811)
  • Smolenskaya Oblast
    • Smolensk, Smolenskaya Oblast, Russian Federation, 214018
      • Smolensk Regional Clinical Hospital ( Site 1800)
  • Stavropol Skiy Kray
    • Stavropol, Stavropol Skiy Kray, Russian Federation, 355029
      • Regional Childrens Clinical Hospital ( Site 1805)
• South Africa
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0208
      • Molotlegi Street ( Site 1903)
  • Kwazulu-Natal
    • Durban, Kwazulu-Natal, South Africa, 4091
      • Inkosi Albert Luthuli Central Hospital ( Site 1902)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7700
      • Red Cross War Memorial Children's Hospital ( Site 1900)
• Turkey
  • Adana, Turkey, 01330
    • Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( Site 2200)
  • Ankara, Turkey, 06230
    • Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2201)
  • Eskisehir, Turkey, 26480
    • Eskisehir Osmangazi Unv. Tip Fakultesi ( Site 2202)
  • Istanbul, Turkey, 34453
    • SBU Sariyer Hamidiye Etfal Egitim ve Arastirma Hastanesi ( Site 2203)
• Ukraine
  • Dnipropetrovska Oblast
    • Dnipro, Dnipropetrovska Oblast, Ukraine, 49100
      • SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 2402)
    • Kryvyy Rig, Dnipropetrovska Oblast, Ukraine, 50082
      • PI Kryvorizka city clinical hospital 8 ( Site 2408)
  • Ivano-Frankivska Oblast
    • Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine, 76014
      • Ivano-Frankivsk Regional Children Clinical Hospital ( Site 2411)
  • Kharkivska Oblast
    • Kharkiv, Kharkivska Oblast, Ukraine, 61037
      • Reg. Clinical Center of Urology and Nephrology n.a. V. I. Shapoval ( Site 2410)
    • Kharkiv, Kharkivska Oblast, Ukraine, 61075
      • Kharkiv City Children Hospital 16 ( Site 2414)
  • Kyivska Oblast
    • Kyiv, Kyivska Oblast, Ukraine, 01135
      • National Children Specialised Hospital OHMADYT MOH Ukraine ( Site 2409)
  • Poltavska Oblast
    • Poltava, Poltavska Oblast, Ukraine, 36004
      • Municipal Institution City Children s Clinical Hospital of Poltava City Council ( Site 2404)
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital - Los Angeles ( Site 2509)
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County ( Site 2502)
    • San Diego, California, United States, 92123
      • Rady Children's Hospital-San Diego ( Site 2505)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 2519)
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Our Lady of the Lake Hospital ( Site 2512)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital ( Site 2508)
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital ( Site 2510)
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health ( Site 2520)
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College Of Medicine ( Site 2515)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a legally acceptable representative who provides documented informed consent / assent for the trial.
• Ages from birth (defined as >32 weeks gestational age and ≥7 days postnatal) to <18 years of age.
• Requires IV antibacterial therapy for the treatment of cUTI.
• Have a pretreatment baseline urine culture specimen obtained within 48 hours before the start of administration of the first dose of study treatment and preferably prior to administration of any potentially therapeutic antibiotics.
• Has pyuria.
• Has clinical signs and/or symptoms of cUTI at the Screening Visit.
• 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 a history of a cUTI 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 nonstudy 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.
• Has any of the following: a) intractable UTI or pyelonephritis infection at baseline that the Investigator anticipates would require more than 14 days of study treatment; b) confirmed fungal urinary tract infection at time of randomization; c) permanent indwelling bladder catheter or instrumentation including nephrostomy; d) current urinary catheter that is not scheduled to be removed before the end of all study treatment; e) complete, permanent obstruction of the urinary tract; f) suspected or confirmed perinephric or intrarenal abscess; g) documented ileal loop reflux; h) suspected or confirmed prostatitis, urethritis, or epididymitis; i) trauma to pelvis/urinary tract.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ceftolozane/Tazobactam; Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days	Drug: Ceftolozane/Tazobactam; 12 to <18 years of age: Ceftolozane 1 g/dose; Tazobactam 0.5 g/dose via a 60-minute (±10 minutes) IV infusion every 8 hours for 7-14 days. <12 years of age: Ceftolozane 20 mg/kg with Tazobactam 10 mg/kg (not to exceed Ceftolozane 1 g and Tazobactam 0.5 g) via a 60-minute (±10 minutes) IV infusion every 8 hours for 7-14 days.
Active Comparator: Meropenem; Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days	Drug: Meropenem; Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for between 7 to 14 days.; Other Names: MERREM®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With ≥1 Adverse Events (AEs)	An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.	Up to Day 88
Number of Participants Discontinuing Study Therapy Due to AE	An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.	Up to Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Clinical Response of Cure at the Test of Cure Visit	Clinical response of cure is complete resolution or marked improvement in signs and symptoms of the complicated urinary tract infection (cUTI) or return to pre-infection signs and symptoms, such that no further antibiotic therapy (IV or oral) is required for the treatment of the cUTI. The 95% confidence intervals (CIs) of each treatment are unstratified Wilson CIs.	Up to Test of Cure Visit (up to 35 days)
Percentage of Participants With a Clinical Response of Cure at the End of Treatment Visit	Clinical response of cure is complete resolution or marked improvement in signs and symptoms of the cUTI or return to pre-infection signs and symptoms, such that no further antibiotic therapy (IV or oral) is required for the treatment of the cUTI. The 95% CIs of each treatment are unstratified Wilson CIs.	Up to 48 hours after last oral dose (up to 19 days)
Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the Test of Cure Visit	Microbiological eradication of all baseline pathogens is defined as a postbaseline urine culture shows all uropathogens found at baseline at ≥10^5 colony-forming units (CFU)/mL are reduced to <10^4 CFU/mL. The 95% CIs of each treatment are unstratified Wilson CIs.	Up to Test of Cure Visit (up to 35 days)
Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the End of Treatment Visit	Microbiological eradication of all baseline pathogens is defined as a postbaseline urine culture shows all uropathogens found at baseline at ≥10^5 colony-forming units (CFU)/mL are reduced to <10^4 CFU/mL. The 95% CIs of each treatment are unstratified Wilson CIs.	Up to 48 hours after last oral dose (up to 19 days)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Roilides E, Ashouri N, Bradley JS, Johnson MG, Lonchar J, Su FH, Huntington JA, Popejoy MW, Bensaci M, De Anda C, Rhee EG, Bruno CJ. Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial. Pediatr Infect Dis J. 2023 Apr 1;42(4):292-298. doi: 10.1097/INF.0000000000003832. Epub 2023 Jan 23.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2018
• Primary Completion (Actual): December 3, 2020
• Study Completion (Actual): December 3, 2020

Study Registration Dates

• First Submitted: July 24, 2017
• First Submitted That Met QC Criteria: July 24, 2017
• First Posted (Actual): July 26, 2017

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 3, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Nephritis; Nephritis, Interstitial; Pyelitis; Infections; Communicable Diseases; Urinary Tract Infections; Pyelonephritis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Meropenem; Tazobactam; Ceftolozane; Ceftolozane, tazobactam drug combination
• Other Study ID Numbers: 7625A-034; 2016-004153-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No