Back to resultsA Safety and Tolerability Study of Doripenem Compared With Cefepime in Children Hospitalized With Complicated Urinary Tract Infections
Primary Purpose
Complicated Urinary Tract Infections or Pyelonephritis
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Doripenem
Doripenem placebo
Cefepime
Cefepime placebo
Amoxicillin/clavulanate potassium
Sponsored by
About this trial
This is an interventional treatment trial for Complicated Urinary Tract Infections or Pyelonephritis focused on measuring Antibiotic, Child, Hospitalized, Complicated Urinary Tract Infection, Pyelonephritis, Doripenem, Cefepime
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Doripenem
Cefepime
Arm Description
Doripenem 20 mg/kg per dose (up to 500 mg/dose) will be administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
Cefepime 50 mg/kg per dose (up to 2 g/dose) will be dministered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
Outcomes
Primary Outcome Measures
The Number of Participants With Clinical Cure Rate at Test Of Cure (TOC) Visit
The participants were classified as cure if they had resolution or clinical improvement in signs and symptoms of complicated urinary tract infection; had no fever; no additional antimicrobial therapy was required for the treatment of the infection; and a clinical response assessment of improvement at End of IV visit.
Secondary Outcome Measures
The Number of Participants With Clinical Improvement Rate at End of IV (EIV) Visit
The participants were considered as clinical improved if they had clinical improvement in signs and symptoms from baseline; no fever for at least the 24 hours before discontinuing the IV study drug; and not received nonstudy antibiotics for the treatment of urinary tract infection after IV study drug therapy had begun.
The Number of Participants With Clinical Cure Rate at Late Follow-Up (LFU) Visit
The participants were classified as clinical cure if all pretreatment signs and symptoms of complicated urinary tract infection showed no evidence of recurrence after test of cure.
The Number of Participants With Favorable Per-participant Microbiological Response
Favorable per-participant microbiological response rate was evaluated at the at End of IV (EIV) visit, Test Of Cure (TOC) visit, and Late Follow-Up (LFU) visit. The favorable per-participant microbiological response was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).A total of 4 pathogens in the doripenem group and 2 pathogens in the cefepime group were isolated at baseline from urine culture and were susceptible to the study drug received (see listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and cefepime treatment groups, respectively).
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment). A total of 4 pathogens in the doripenem group and 2 pathogens in the cefepime group were isolated at baseline from urine culture and were susceptible to the study drug received (see listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and cefepime treatment groups, respectively).
Number of Participants With Sustained Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
The sustained favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment). A total of 4 pathogens in the doripenem group and 2 pathogens in the cefepime group were isolated at baseline from urine culture and were susceptible to the study drug received (see listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and cefepime treatment groups, respectively).
Full Information
NCT ID
NCT01110408
First Posted
April 15, 2010
Last Updated
July 2, 2014
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT01110408
Brief Title
A Safety and Tolerability Study of Doripenem Compared With 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 Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Terminated
Why Stopped
Trial terminated early per business decision
Study Start Date
December 2010 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Complicated Urinary Tract Infections or Pyelonephritis
Keywords
Antibiotic, Child, Hospitalized, Complicated Urinary Tract Infection, Pyelonephritis, Doripenem, Cefepime
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Doripenem
Arm Type
Experimental
Arm Description
Doripenem 20 mg/kg per dose (up to 500 mg/dose) will be administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
Arm Title
Cefepime
Arm Type
Experimental
Arm Description
Cefepime 50 mg/kg per dose (up to 2 g/dose) will be dministered every 8 hours as 30-minutes IV (at least 3 days of IV cefepime only or IV cefepime followed by oral amoxicillin/clavulanate potassium or ciprofloxacin). Total duration of treatment 10 to 14 days.
Intervention Type
Drug
Intervention Name(s)
Doripenem
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Doripenem placebo
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Cefepime
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Cefepime placebo
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Amoxicillin/clavulanate potassium
Intervention Description
Form=suspension or tablets, Route=oral (by mouth), may be administered at the discretion of the investigator once every 12 hours for up to 14 days following IV therapy with doripenem or cefepime.
Primary Outcome Measure Information:
Title
The Number of Participants With Clinical Cure Rate at Test Of Cure (TOC) Visit
Description
The participants were classified as cure if they had resolution or clinical improvement in signs and symptoms of complicated urinary tract infection; had no fever; no additional antimicrobial therapy was required for the treatment of the infection; and a clinical response assessment of improvement at End of IV visit.
Time Frame
TOC (7 to 14 days after the last dose of study medication therapy)
Secondary Outcome Measure Information:
Title
The Number of Participants With Clinical Improvement Rate at End of IV (EIV) Visit
Description
The participants were considered as clinical improved if they had clinical improvement in signs and symptoms from baseline; no fever for at least the 24 hours before discontinuing the IV study drug; and not received nonstudy antibiotics for the treatment of urinary tract infection after IV study drug therapy had begun.
Time Frame
EIV (within 24 hours after completion of the last dose of IV study medication therapy)
Title
The Number of Participants With Clinical Cure Rate at Late Follow-Up (LFU) Visit
Description
The participants were classified as clinical cure if all pretreatment signs and symptoms of complicated urinary tract infection showed no evidence of recurrence after test of cure.
Time Frame
LFU (28 to 42 days after the last dose of study medication therapy)
Title
The Number of Participants With Favorable Per-participant Microbiological Response
Description
Favorable per-participant microbiological response rate was evaluated at the at End of IV (EIV) visit, Test Of Cure (TOC) visit, and Late Follow-Up (LFU) visit. The favorable per-participant microbiological response was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
Time Frame
EIV (within 24 hours after completion of the last dose of IV study medication therapy), TOC (7 to 14 days after the last dose of study medication therapy), and LFU (28 to 42 days after the last dose of study medication therapy)
Title
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
Description
The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).A total of 4 pathogens in the doripenem group and 2 pathogens in the cefepime group were isolated at baseline from urine culture and were susceptible to the study drug received (see listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and cefepime treatment groups, respectively).
Time Frame
EIV (within 24 hours after completion of the last dose of IV study medication therapy)
Title
Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
Description
The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment). A total of 4 pathogens in the doripenem group and 2 pathogens in the cefepime group were isolated at baseline from urine culture and were susceptible to the study drug received (see listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and cefepime treatment groups, respectively).
Time Frame
TOC (7 to 14 days after the last dose of study medication therapy)
Title
Number of Participants With Sustained Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
Description
The sustained favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment). A total of 4 pathogens in the doripenem group and 2 pathogens in the cefepime group were isolated at baseline from urine culture and were susceptible to the study drug received (see listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and cefepime treatment groups, respectively).
Time Frame
LFU (28 to 42 days after the last dose of study medication therapy)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC C. Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Little Rock
State/Province
Arkansas
Country
United States
City
Oakland
State/Province
California
Country
United States
City
Orange
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
Washington
State/Province
District of Columbia
Country
United States
City
New Brunswick
State/Province
New Jersey
Country
United States
City
Albany
State/Province
New York
Country
United States
City
Bronx
State/Province
New York
Country
United States
City
Cleveland
State/Province
Ohio
Country
United States
City
Toledo
State/Province
Ohio
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
City
Buenos Aires
Country
Argentina
City
Córdoba
Country
Argentina
City
Loma Hermosa N/A
Country
Argentina
City
Santa Fe
Country
Argentina
City
Belo Horizonte
Country
Brazil
City
Caxias Do Sul
Country
Brazil
City
Passo Fundo
Country
Brazil
City
São Paulo
Country
Brazil
City
Santiago
Country
Chile
City
Valdivia X Región
Country
Chile
City
Bogota
Country
Colombia
City
Cali
Country
Colombia
City
Floridablanca
Country
Colombia
City
Medellin
Country
Colombia
City
Hradec Kralove
Country
Czech Republic
City
Praha
Country
Czech Republic
City
Riga
Country
Latvia
City
Kaunas
Country
Lithuania
City
Vilnius
Country
Lithuania
City
Guadajalara
Country
Mexico
City
Monterrey
Country
Mexico
City
Zapopan
Country
Mexico
City
Zona
Country
Panama
City
Lublin
Country
Poland
City
Szczecin
Country
Poland
City
Kharkiv
Country
Ukraine
City
Poltava
Country
Ukraine
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=3412&filename=CR100747_CSR.pdf
Description
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Learn more about this trial
A Safety and Tolerability Study of Doripenem Compared With Cefepime in Children Hospitalized With Complicated Urinary Tract Infections
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