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

NCT03230838 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 7625A-0342016-004153-32
• Study Type: interventional
• Target: 134
• Locations: 10 countries
• Sites: 52

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.

Conditions

Complicated Urinary Tract Infection; Pyelonephritis

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Percentage of Participants With a Clinical Response of Cure at the Test of Cure Visit

  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

  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

  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

  Up to 48 hours after last oral dose (up to 19 days)

Study Arms (2)

Ceftolozane/Tazobactam

EXPERIMENTAL

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

Meropenem

ACTIVE COMPARATOR

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

Drug: Meropenem

Interventions

Ceftolozane/Tazobactam DRUG

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.

Ceftolozane/Tazobactam

Meropenem DRUG

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

Also known as: MERREM®

Meropenem

Eligibility Criteria

• Age: 7 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (52)

Children's Hospital - Los Angeles ( Site 2509)

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County ( Site 2502)

Orange, California, 92868, United States

Location

Rady Children's Hospital-San Diego ( Site 2505)

San Diego, California, 92123, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 2519)

Chicago, Illinois, 60611, United States

Location

Our Lady of the Lake Hospital ( Site 2512)

Baton Rouge, Louisiana, 70808, United States

Location

St. Louis Children's Hospital ( Site 2508)

St Louis, Missouri, 63110, United States

Location

SUNY Upstate Medical University Hospital ( Site 2510)

Syracuse, New York, 13210, United States

Location

Wake Forest Baptist Health ( Site 2520)

Winston-Salem, North Carolina, 27157, United States

Location

Baylor College Of Medicine ( Site 2515)

Houston, Texas, 77030, United States

Location

Pan and Aglaia Kyriakou Children s Hospital ( Site 0780)

Athens, Attica, 115 27, Greece

Location

University of Athens - Aghia Sophia Childrens Hospital ( Site 0730)

Athens, Attica, 115 27, Greece

Location

Athens University Hospital ATTIKON ( Site 0790)

Athens, Attica, 124 62, Greece

Location

Hippokration General Hospital of Thessaloniki ( Site 0700)

Thessaloniki, Thessaloníki, 546 42, Greece

Location

General University Hospital of Larissa ( Site 0740)

Larissa, Thessaly, 411 10, Greece

Location

PTE AOK Klinikai Kozpont ( Site 0809)

Pécs, Baranya, 7623, Hungary

Location

SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0804)

Szeged, Csongrád megye, 6720, Hungary

Location

SzSzBMK es Egyetemi Oktatokorhaz Josa Andras Oktatokorhaz ( Site 0808)

Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary

Location

Semmelweis Egyetem ( Site 0810)

Budapest, 1083, Hungary

Location

Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 0801)

Budapest, 1089, Hungary

Location

Debreceni Egyetem Klinikai Kozpont ( Site 0803)

Debrecen, 4032, Hungary

Location

Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 1202)

Guadalajara, Jalisco, 44280, Mexico

Location

Instituto Tecnologico y de Estudios Superiores de Monterrey ( Site 1204)

Monterrey, Nuevo León, 64710, Mexico

Location

Instituto Nacional de Pediatria ( Site 1201)

Mexico City, 04530, Mexico

Location

Hospital Infantil de Mexico Federico Gomez ( Site 1203)

Mexico City, 06720, Mexico

Location

Wojewodzki Szpital Obserwacyjno Zakazny ( Site 1606)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-030, Poland

Location

Szpital Uniwersytecki nr 1 im. Dr. Antoniego Jurasza w Bydgoszczy ( Site 1600)

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-094, Poland

Location

Wojewodzki Szpital Zespolony im. Rydgiera ( Site 1607)

Torun, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

Location

Uniw. Szpital Dzieciecy w Krakowie ( Site 1609)

Krakow, Lesser Poland Voivodeship, 30-663, Poland

Location

SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 1608)

Łomianki, Masovian Voivodeship, 05-092, Poland

Location

Instytut Centrum Zdrowia Matki Polki ( Site 1602)

Lodz, Łódź Voivodeship, 93-338, Poland

Location

Spitalul Clinic de Urgenta pentru Copii Maria Sklodowska Curie ( Site 1707)

Bucharest, București, 041451, Romania

Location

Spit. Cl. de Urg. Copii Cluj Napoca ( Site 1708)

Cluj-Napoca, Cluj, 400177, Romania

Location

Spitalul Clinic de Urgenta pentru Copii Brasov ( Site 1703)

Brasov, 500063, Romania

Location

Institutul National de Boli Infectioase Prof. Dr. Matei Bals ( Site 1706)

Bucharest, 021106, Romania

Location

Russian Pediatric Clinical Hospital ( Site 1808)

Moscow, Moscow, 119571, Russia

Location

St.Petersburg State Pediatric Medical University ( Site 1811)

Saint Petersburg, Sankt-Peterburg, 194100, Russia

Location

Smolensk Regional Clinical Hospital ( Site 1800)

Smolensk, Smolensk Oblast, 214018, Russia

Location

Regional Childrens Clinical Hospital ( Site 1805)

Stavropol, Stavropol Kray, 355029, Russia

Location

Molotlegi Street ( Site 1903)

Pretoria, Gauteng, 0208, South Africa

Location

Inkosi Albert Luthuli Central Hospital ( Site 1902)

Durban, KwaZulu-Natal, 4091, South Africa

Location

Red Cross War Memorial Children's Hospital ( Site 1900)

Cape Town, Western Cape, 7700, South Africa

Location

Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( Site 2200)

Adana, 01330, Turkey (Türkiye)

Location

Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2201)

Ankara, 06230, Turkey (Türkiye)

Location

Eskisehir Osmangazi Unv. Tip Fakultesi ( Site 2202)

Eskişehir, 26480, Turkey (Türkiye)

Location

SBU Sariyer Hamidiye Etfal Egitim ve Arastirma Hastanesi ( Site 2203)

Istanbul, 34453, Turkey (Türkiye)

Location

SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 2402)

Dnipro, Dnipropetrovsk Oblast, 49100, Ukraine

Location

PI Kryvorizka city clinical hospital 8 ( Site 2408)

Kryvyy Rig, Dnipropetrovsk Oblast, 50082, Ukraine

Location

Ivano-Frankivsk Regional Children Clinical Hospital ( Site 2411)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76014, Ukraine

Location

Reg. Clinical Center of Urology and Nephrology n.a. V. I. Shapoval ( Site 2410)

Kharkiv, Kharkivs’ka Oblast’, 61037, Ukraine

Location

Kharkiv City Children Hospital 16 ( Site 2414)

Kharkiv, Kharkivs’ka Oblast’, 61075, Ukraine

Location

National Children Specialised Hospital OHMADYT MOH Ukraine ( Site 2409)

Kyiv, Kyivska Oblast, 01135, Ukraine

Location

Municipal Institution City Children s Clinical Hospital of Poltava City Council ( Site 2404)

Poltava, Poltava Oblast, 36004, Ukraine

Location

Related 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 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.

  PMID: 36689671 RESULT

MeSH Terms

Conditions

Pyelonephritis

Interventions

ceftolozane, tazobactam drug combination; Meropenem

Condition Hierarchy (Ancestors)

Nephritis, Interstitial; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pyelitis; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2017
• First Posted: July 26, 2017
• Study Start: April 26, 2018
• Primary Completion: December 3, 2020
• Study Completion: December 3, 2020
• Last Updated: May 6, 2023
• Results First Posted: December 1, 2021

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share

Locations

RO (4); PL (6); ZA (3); TU (4); HU (6); GR (5); ME (4); UA (7); US (9); RU (4)