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

Pyelonephritis 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) Versus Meropenem in Pediatric Subjects With Complicated Urinary Tract Infection, Including Pyelonephritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03230838
• Other study ID #: 7625A-034
• Secondary ID: 2016-004153-32
• Status: Completed
• Phase: Phase 2
• Start date: April 26, 2018
• Est. completion date: December 3, 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) compared with that of meropenem in pediatric participants with cUTI, including pyelonephritis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 134
• Est. completion date: December 3, 2020
• Est. primary completion date: December 3, 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.

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

Related Conditions & MeSH terms

• Communicable Diseases
• Complicated Urinary Tract Infection
• Infections
• Pyelonephritis
• Urinary Tract Infections

Intervention

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.
• Meropenem
Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for between 7 to 14 days.

Locations

Country	Name	City	State
Greece	Athens University Hospital ATTIKON ( Site 0790)	Athens	Attiki
Greece	Pan and Aglaia Kyriakou Children s Hospital ( Site 0780)	Athens	Attiki
Greece	University of Athens - Aghia Sophia Childrens Hospital ( Site 0730)	Athens	Attiki
Greece	General University Hospital of Larissa ( Site 0740)	Larissa	Thessalia
Greece	Hippokration General Hospital of Thessaloniki ( Site 0700)	Thessaloniki	Thessaloníki
Hungary	Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0801)	Budapest
Hungary	Semmelweis Egyetem ( Site 0810)	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont ( Site 0803)	Debrecen
Hungary	SzSzBMK es Egyetemi Oktatokorhaz Josa Andras Oktatokorhaz ( Site 0808)	Nyiregyhaza	Szabolcs-Szatmar-Bereg
Hungary	PTE AOK Klinikai Kozpont ( Site 0809)	Pecs	Baranya
Hungary	SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0804)	Szeged	Csongrad
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 1202)	Guadalajara	Jalisco
Mexico	Hospital Infantil de Mexico Federico Gomez ( Site 1203)	Mexico City
Mexico	Instituto Nacional de Pediatria ( Site 1201)	Mexico City
Mexico	Instituto Tecnologico y de Estudios Superiores de Monterrey ( Site 1204)	Monterrey	Nuevo Leon
Poland	Szpital Uniwersytecki nr 1 im. Dr. Antoniego Jurasza w Bydgoszczy ( Site 1600)	Bydgoszcz	Kujawsko-pomorskie
Poland	Wojewodzki Szpital Obserwacyjno Zakazny ( Site 1606)	Bydgoszcz	Kujawsko-pomorskie
Poland	Uniw. Szpital Dzieciecy w Krakowie ( Site 1609)	Krakow	Malopolskie
Poland	Instytut Centrum Zdrowia Matki Polki ( Site 1602)	Lodz	Lodzkie
Poland	SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 1608)	Lomianki	Mazowieckie
Poland	Wojewodzki Szpital Zespolony im. Rydgiera ( Site 1607)	Torun	Kujawsko-pomorskie
Romania	Spitalul Clinic de Urgenta pentru Copii Brasov ( Site 1703)	Brasov
Romania	Spitalul Clinic de Urgenta pentru Copii Maria Sklodowska Curie ( Site 1707)	Bucharest	Bucuresti
Romania	Institutul National de Boli Infectioase Prof. Dr. Matei Bals ( Site 1706)	Bucuresti
Romania	Spit. Cl. de Urg. Copii Cluj Napoca ( Site 1708)	Cluj-Napoca	Cluj
Russian Federation	Russian Pediatric Clinical Hospital ( Site 1808)	Moscow	Moskva
Russian Federation	St.Petersburg State Pediatric Medical University ( Site 1811)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Smolensk Regional Clinical Hospital ( Site 1800)	Smolensk	Smolenskaya Oblast
Russian Federation	Regional Childrens Clinical Hospital ( Site 1805)	Stavropol	Stavropol Skiy Kray
South Africa	Red Cross War Memorial Children's Hospital ( Site 1900)	Cape Town	Western Cape
South Africa	Inkosi Albert Luthuli Central Hospital ( Site 1902)	Durban	Kwazulu-Natal
South Africa	Molotlegi Street ( Site 1903)	Pretoria	Gauteng
Turkey	Cukurova Universitesi Tip Fakultesi Balcali Hastanesi ( 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 2402)	Dnipro	Dnipropetrovska Oblast
Ukraine	Ivano-Frankivsk Regional Children Clinical Hospital ( Site 2411)	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	Kharkiv City Children Hospital 16 ( Site 2414)	Kharkiv	Kharkivska Oblast
Ukraine	Reg. Clinical Center of Urology and Nephrology n.a. V. I. Shapoval ( Site 2410)	Kharkiv	Kharkivska Oblast
Ukraine	PI Kryvorizka city clinical hospital 8 ( Site 2408)	Kryvyy Rig	Dnipropetrovska Oblast
Ukraine	National Children Specialised Hospital OHMADYT MOH Ukraine ( Site 2409)	Kyiv	Kyivska Oblast
Ukraine	Municipal Institution City Children s Clinical Hospital of Poltava City Council ( Site 2404)	Poltava	Poltavska Oblast
United States	Our Lady of the Lake Hospital ( Site 2512)	Baton Rouge	Louisiana
United States	Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 2519)	Chicago	Illinois
United States	Baylor College Of Medicine ( Site 2515)	Houston	Texas
United States	Children's Hospital - Los Angeles ( Site 2509)	Los Angeles	California
United States	Children's Hospital of Orange County ( Site 2502)	Orange	California
United States	St. Louis Children's Hospital ( Site 2508)	Saint Louis	Missouri
United States	Rady Children's Hospital-San Diego ( Site 2505)	San Diego	California
United States	SUNY Upstate Medical University Hospital ( Site 2510)	Syracuse	New York
United States	Wake Forest Baptist Health ( Site 2520)	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Greece,  Hungary,  Mexico,  Poland,  Romania,  Russian Federation,  South Africa,  Turkey,  Ukraine, 

References & Publications (1)

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 Inf — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)