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

This study has been terminated.
(Trial terminated early per business decision)
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01110408
First received: April 15, 2010
Last updated: October 14, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Complicated Urinary Tract Infections or Pyelonephritis
Drug: doripenem
Drug: doripenem placebo
Drug: cefepime
Drug: cefepime placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Adverse events [ Time Frame: Baseline up to 42 days after the last dose of study drug ] [ Designated as safety issue: No ]
  • Clinical laboratory tests [ Time Frame: Baseline up to 42 days after the last dose of study drug ] [ Designated as safety issue: No ]
  • Vital signs measurements [ Time Frame: Baseline up to 42 days after the last dose of study drug ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 7 to 14 days after the last dose of iv study drug including oral antibiotic therapy ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Within 24 hours after completion of the last dose of iv study drug ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 28 to 42 days after the last dose of iv study drug including oral antibiotic therapy ] [ Designated as safety issue: No ]
  • To characterize the pharmacokinetics of doripenem in hospitalized children with cUTI on the basis of a sparse pharmacokinetic sampling scheme [ Time Frame: 1, 2, 4 and 6 hours after the 4th, 5th, 6th, or 7th dose administrations of doripenem/doripenem placebo ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: December 2010
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cefepime placebo/Doripenem
Patients will receive at least 3 days of iv doripenem administered every 8 hours immediately after each iv infusion of cefepime placebo for up to 14 days.
Drug: doripenem
Type=once every 8 hours infused over 60 minutes, Unit=mg,Number=20mg/kg up to 500mg/dose, Form=solution for infusion,Route=intravenous use. At least 3 days of iv doripenem administered every 8 hours immediately after each iv infusion of cefepime placebo for up to 14 days
Drug: cefepime placebo
Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 30 minutes immediately before each iv infusion of doripenem for up to 14 days
Experimental: Cefepime/Doripenem placebo
Patients will receive at least 3 days of iv cefepime administered every 8 hours infused over 30 minutes immediately before each iv infusion of doripenem placebo for up to 14 days.
Drug: doripenem placebo
Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 60 minutes immediately following each iv infusion of cefepime for up to 14 days
Drug: cefepime
Type=once every 8 hours, Unit=mg, Number=50 mg/kg up to 2g/dose, Form=solution for infusion, Route=intravenous use. At least 3 days of iv cefepime administered every 8 hours infused over 30 minutes immediately before each iv infusion of doripenem placebo for up to 14 days

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.

  Eligibility

Ages Eligible for Study:   3 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01110408

  Show 39 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC C. Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01110408     History of Changes
Other Study ID Numbers: CR016792, DORIPED3002, 2009-015953-18
Study First Received: April 15, 2010
Last Updated: October 14, 2013
Health Authority: United States: Food and Drug Administration
Latvia: State Agency of Medicines
Ukraine: State Pharmacological Center - Ministry of Health
United States: Federal Government

Keywords provided by Janssen Research & Development, LLC:
Antibiotic
Child, Hospitalized
Complicated Urinary Tract Infection
Pyelonephritis
Doripenem
Cefepime

Additional relevant MeSH terms:
Pyelonephritis
Urinary Tract Infections
Nephritis, Interstitial
Nephritis
Kidney Diseases
Urologic Diseases
Pyelitis
Infection
Cefepime
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014