Clinical trial NCT03230838: MK-7625A Versus Meropenem in Pediatric Participants With Complicated Urinary Tract Infection (cUTI) (MK-7625A-034)
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) Versus Meropenem in Pediatric Subjects With Complicated Urinary Tract Infection, Including Pyelonephritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Complicated Urinary Tract Infection
Pyelonephritis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-07-26
Enrollment: 134
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) compared with that of meropenem in pediatric participants with cUTI, including pyelonephritis.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With ≥1 Adverse Events (AEs)
timeFrame: Up to Day 88
measure: Number of Participants Discontinuing Study Therapy Due to AE
timeFrame: Up to Day 15
Secondary outcomes:
measure: Percentage of Participants With a Clinical Response of Cure at the Test of Cure Visit
timeFrame: Up to Test of Cure Visit (up to 35 days)
measure: Percentage of Participants With a Clinical Response of Cure at the End of Treatment Visit
timeFrame: Up to 48 hours after last oral dose (up to 19 days)
measure: Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the Test of Cure Visit
timeFrame: Up to Test of Cure Visit (up to 35 days)
measure: Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the End of Treatment Visit
timeFrame: Up to 48 hours after last oral dose (up to 19 days)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital - Los Angeles ( Site 2509)
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: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 2519)
state: Illinois
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Hospital ( Site 2512)
state: Louisiana
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital ( Site 2508)
state: Missouri
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital ( Site 2510)
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health ( Site 2520)
state: North Carolina
city: Houston
country: United States
facility: Baylor College Of Medicine ( Site 2515)
state: Texas
city: Athens
country: Greece
facility: Pan and Aglaia Kyriakou Children s Hospital ( Site 0780)
state: Attiki
city: Athens
country: Greece
facility: University of Athens - Aghia Sophia Childrens Hospital ( Site 0730)
state: Attiki
city: Athens
country: Greece
facility: Athens University Hospital ATTIKON ( Site 0790)
state: Attiki
city: Larissa
country: Greece
facility: General University Hospital of Larissa ( Site 0740)
state: Thessalia
city: Thessaloniki
country: Greece
facility: Hippokration General Hospital of Thessaloniki ( Site 0700)
state: Thessaloníki
city: Pecs
country: Hungary
facility: PTE AOK Klinikai Kozpont ( Site 0809)
state: Baranya
city: Szeged
country: Hungary
facility: SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0804)
state: Csongrad
city: Nyiregyhaza
country: Hungary
facility: SzSzBMK es Egyetemi Oktatokorhaz Josa Andras Oktatokorhaz ( Site 0808)
state: Szabolcs-Szatmar-Bereg
city: Budapest
country: Hungary
facility: Semmelweis Egyetem ( Site 0810)
city: Budapest
country: Hungary
facility: Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0801)
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont ( Site 0803)
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 1202)
state: Jalisco
city: Monterrey
country: Mexico
facility: Instituto Tecnologico y de Estudios Superiores de Monterrey ( Site 1204)
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 1203)
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital Obserwacyjno Zakazny ( Site 1606)
state: Kujawsko-pomorskie
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 1 im. Dr. Antoniego Jurasza w Bydgoszczy ( Site 1600)
state: Kujawsko-pomorskie
city: Torun
country: Poland
facility: Wojewodzki Szpital Zespolony im. Rydgiera ( Site 1607)
state: Kujawsko-pomorskie
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki ( Site 1602)
state: Lodzkie
city: Krakow
country: Poland
facility: Uniw. Szpital Dzieciecy w Krakowie ( Site 1609)
state: Malopolskie
city: Lomianki
country: Poland
facility: SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 1608)
state: Mazowieckie
city: Bucharest
country: Romania
facility: Spitalul Clinic de Urgenta pentru Copii Maria Sklodowska Curie ( Site 1707)
state: Bucuresti
city: Cluj-Napoca
country: Romania
facility: Spit. Cl. de Urg. Copii Cluj Napoca ( Site 1708)
state: Cluj
city: Brasov
country: Romania
facility: Spitalul Clinic de Urgenta pentru Copii Brasov ( Site 1703)
city: Bucuresti
country: Romania
facility: Institutul National de Boli Infectioase Prof. Dr. Matei Bals ( Site 1706)
city: Moscow
country: Russian Federation
facility: Russian Pediatric Clinical Hospital ( Site 1808)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: St.Petersburg State Pediatric Medical University ( Site 1811)
state: Sankt-Peterburg
city: Smolensk
country: Russian Federation
facility: Smolensk Regional Clinical Hospital ( Site 1800)
state: Smolenskaya Oblast
city: Stavropol
country: Russian Federation
facility: Regional Childrens Clinical Hospital ( Site 1805)
state: Stavropol Skiy Kray
city: Pretoria
country: South Africa
facility: Molotlegi Street ( Site 1903)
state: Gauteng
city: Durban
country: South Africa
facility: Inkosi Albert Luthuli Central Hospital ( Site 1902)
state: Kwazulu-Natal
city: Cape Town
country: South Africa
facility: Red Cross War Memorial Children's Hospital ( Site 1900)
state: Western Cape
city: Adana
country: Turkey
facility: Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( 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 2402)
state: Dnipropetrovska Oblast
city: Kryvyy Rig
country: Ukraine
facility: PI Kryvorizka city clinical hospital 8 ( Site 2408)
state: Dnipropetrovska Oblast
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Children Clinical Hospital ( Site 2411)
state: Ivano-Frankivska Oblast
city: Kharkiv
country: Ukraine
facility: Reg. Clinical Center of Urology and Nephrology n.a. V. I. Shapoval ( Site 2410)
state: Kharkivska Oblast
city: Kharkiv
country: Ukraine
facility: Kharkiv City Children Hospital 16 ( Site 2414)
state: Kharkivska Oblast
city: Kyiv
country: Ukraine
facility: National Children Specialised Hospital OHMADYT MOH Ukraine ( Site 2409)
state: Kyivska Oblast
city: Poltava
country: Ukraine
facility: Municipal Institution City Children s Clinical Hospital of Poltava City Council ( Site 2404)
state: Poltavska Oblast
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.