A Safety and Tolerability Study of Doripenem Compared With Cefepime in Children Hospitalized With Complicated Urinary Tract Infections

Condition(s) targeted: Complicated Urinary Tract Infections or Pyelonephritis

Intervention: doripenem (Drug); doripenem placebo (Drug); cefepime (Drug); cefepime placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Janssen Research & Development, LLC

Official(s) and/or principal investigator(s):
Janssen Research & Development, LLC C. Clinical Trial, Study Director, Affiliation: Janssen Research & Development, LLC

Overall contact:
Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:, Email: JNJ.CT@sylogent.com

The purpose of this study is to evaluate the safety and tolerability of doripenem compared to cefepime in children hospitalized with complicated urinary tract infections.

Official title: A Prospective, Randomized, Double-Blind, Multicenter Study to Establish the Safety and Tolerability of Doripenem Compared With Cefepime in Hospitalized Children With Complicated Urinary Tract Infections

Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Adverse events

Clinical laboratory tests

Vital signs measurements

Secondary outcome:

To determine the clinical cure rate and favorable microbiological response rate of doripenem compared with that of cefepime at the test of cure (TOC) visit

To determine the clinical improvement rate and favorable microbiological response rate of doripenem compared with that of cefepime at the end of treatment with iv study drug therapy (EIV) visit

To determine the sustained clinical cure rate and favorable microbiological response rate of doripenem compared with that of cefepime at the late follow-up (LFU) visit

To characterize the pharmacokinetics of doripenem in hospitalized children with cUTI on the basis of a sparse pharmacokinetic sampling scheme

Detailed description: This is a randomized (study assigned by chance), double-blind (neither physician nor patient knows the name of the assigned study drugs), double-dummy (all patients are given both a placebo [salt solution] and study drug in alternating periods of time during the study), active comparator-controlled (compare the 'test' treatment to standard-of-care therapy), multinational, multicenter study to establish the safety and tolerability of the antibiotic doripenem compared with the antibiotic cefepime administered by intravenous (iv) infusion (slow injection of drug solution into the vein over a period of time) in children ages 3 months to less than 18 years hospitalized with a complicated urinary tract infection (cUTI). The study includes 3 periods: a pretreatment (screening) period that will occur within 2 days prior to randomization (assignment of study drug); a treatment period of 10 to 14 days where the patients will receive study drug treatment, and a posttreatment period consisting of 2 study visits. The maximum duration of study drug therapy is 14 days. The total duration of the study is approximately 7 to 8 weeks for each patient. Safety and tolerability will be evaluated by examining the incidence, severity, and type of adverse events, changes in clinical laboratory tests, vital sign measurements, and findings from physical examinations that are recorded as adverse events during treatment and at each posttreatment visit. An independent monitoring committee (IDMC) will be established for this study to ensure that the safety of patients is not compromised. The IDMC will consist of individuals who are not associated with the conduct of the study, and will include but will not be limited to individuals with expertise relevant to the care of pediatric patients, and including at least one infectious disease physician and at least one statistician. IV study drug therapy (Cefepime [50mg/kg up to 2g/dose] and doripenem placebo or doripenem [20mg/kg up to 500mg/dose] and cefepime placebo will be administered once every 8 hours for up to 14 days. After receiving a minimum of 3 days of IV study drug therapy, patients may be discharged from the hospital and continue PO antibiotic therapy with amoxicillin/clavulanate potassium, ciprofloxacin, or alternative antibiotic therapy.

Minimum age: 3 Months. Maximum age: 18 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients who are eligible for the study must have a current episode of cUTI or

pyelonephritis

- Have evidence of pyuria that meets criteria specified in the study protocol

- Have a study-qualifying pretreatment "baseline" urine culture specimen obtained by an

acceptable method within 48 hours before the start of the administration of the first dose of iv study drug from which a bacterial pathogen is isolated with a growth of >= 100000 colony forming units (CFU)/mL

- Require hospitalization initially and 10 to 14 days of antibacterial therapy [of

which at least 72 hours should be iv therapy] for the treatment of the presumed UTI

- Have a signed informed consent form completed by the patient's parent or legal

representative (and a signed assent form obtained from patients who are capable of providing assent, typically, children 7 years of age or older)

Exclusion Criteria:

- Have a history of hypersensitivity reactions to carbapenems, cephalosporins,

penicillins, or other beta-lactam antibiotics

- concomitant infection including but not limited to suspected or confirmed meningitis

or central nervous system infection requiring systemic antibiotic or antifungal therapy in addition to the iv study drug therapy at the time of randomization

- Receipt of any amount of systemic antibiotic within 96 hours before obtaining the

study-qualifying pretreatment baseline urine or systemic antibiotic therapy for more than 24 hours after obtaining the study-qualifying pretreatment baseline urine specimen

- Have a diagnosis of intractable UTI/pyelonephritis infection anticipated to require

more than 14 days of study drug therapy, a permanent indwelling bladder catheter or instrumentation including nephrostomy or current urinary catheter that will not be removed or anticipation of urinary catheter placement that will not be removed during the course of iv study drug therapy administration, complete and permanent obstruction of the urinary tract, confirmed fungal UTI, suspected or confirmed perinephric or intrarenal abscess, suspected or confirmed prostatitis, known ileal loops, or any of the following clinically significant laboratory abnormalities: absolute neutrophil count (ANC) <500 cells/µL, platelet count <40,000 cells/µL, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin >5x the age-specific upper limit of normal (ULN), acute or chronic renal insufficiency with a baseline creatinine clearance <60 mL per minute or requires dialysis therapy for any reason

- Have a history of uncontrolled epilepsy defined as at least 1 seizure within the 6

months before randomization

Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:, Email: JNJ.CT@sylogent.com

Buenos Aires, Argentina; Completed

Buenos Aires N/A, Argentina; Completed

Córdoba, Argentina; Withdrawn

La Capital, Argentina; Recruiting

Loma Hermosa N/A, Argentina; Recruiting

Paraná, Entre Ríos, Argentina; Withdrawn

Santa Fe, Argentina; Withdrawn

Belo Horizonte, Brazil; Withdrawn

Campinas, Brazil; Not yet recruiting

Caxias Do Sul, Brazil; Recruiting

Passo Fundo, Brazil; Recruiting

São Paulo, Brazil; Withdrawn

Santiago, Chile; Suspended

Valdivia X Región, Chile; Suspended

Armenia, Colombia; Withdrawn

Bogota, Colombia; Withdrawn

Bogotá, Colombia; Withdrawn

Cali, Colombia; Recruiting

Floridablanca, Colombia; Not yet recruiting

Medellin, Colombia; Recruiting

Hradec Kralove, Czech Republic; Recruiting

Praha, Czech Republic; Recruiting

Erlangen, Germany; Withdrawn

Frankfurt, Germany; Withdrawn

Köln, Germany; Withdrawn

Tübingen, Germany; Not yet recruiting

Bangalore, India; Not yet recruiting

Ludhiana, India; Not yet recruiting

Mangalore, India; Withdrawn

Nagpur, India; Not yet recruiting

Pune, India; Not yet recruiting

Secunderabad, India; Withdrawn

Riga, Latvia; Recruiting

Kaunas, Lithuania; Recruiting

Vilnius, Lithuania; Recruiting

Guadajalara, Mexico; Recruiting

Mexico, Mexico; Not yet recruiting

Monterrey, Mexico; Recruiting

Zapopan, Mexico; Completed

Zona, Panama; Recruiting

Lodz, Poland; Withdrawn

Lublin, Poland; Recruiting

Szczecin, Poland; Withdrawn

Kampala, Uganda; Withdrawn

Kharkiv, Ukraine; Recruiting

Kharkov, Ukraine; Recruiting

Kiev, Ukraine; Withdrawn

Lviv, Ukraine; Withdrawn

Poltava, Ukraine; Recruiting

Uzhgorod, Ukraine; Withdrawn

Little Rock, Arkansas, United States; Recruiting

Oakland, California, United States; Completed

Orange, California, United States; Recruiting

San Diego, California, United States; Recruiting

Aurora, Colorado, United States; Withdrawn

Washington, District of Columbia, United States; Recruiting

Chicago, Illinois, United States; Withdrawn

South Bend, Indiana, United States; Withdrawn

New Orleans, Louisiana, United States; Withdrawn

Boston, Massachusetts, United States; Withdrawn

Royal Oak, Michigan, United States; Withdrawn

Omaha, Nebraska, United States; Withdrawn

New Brunswick, New Jersey, United States; Recruiting

Albany, New York, United States; Completed

Bronx, New York, United States; Recruiting

New York, New York, United States; Withdrawn

Akron, Ohio, United States; Withdrawn

Cleveland, Ohio, United States; Recruiting

Toledo, Ohio, United States; Recruiting

Pittsburgh, Pennsylvania, United States; Recruiting

To learn how to participate in this trial please click here.

Starting date: December 2010
Last updated: February 1, 2013