Complicated Urinary Tract Infections or PyelonephritisPhase 3NCT01110408
A Safety and Tolerability Study of Doripenem Compared With Cefepime in Children Hospitalized With Complicated Urinary Tract Infections
A Phase 3 study testing Doripenem, Cefepime and Amoxicillin/clavulanate potassium in people with Complicated Urinary Tract Infections or Pyelonephritis, run by Janssen Research & Development, LLC at 38 sites in 12 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 months to 18 years
- Conditions the study is for
- Complicated Urinary Tract Infections or Pyelonephritis
- What is being tested?
- Doripenem, Cefepime and Amoxicillin/clavulanate potassium
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 38 sitesin 12 countries
- Study dates
- Dec 2010to Jun 2013
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
38 sites in 12 countries.
38 sites in 12 countries
United States11 sites
Study site
Albany, New York
Study site
Cleveland, Ohio
Study site
Little Rock, Arkansas
Study site
New Brunswick, New Jersey
Study site
Oakland, California
Study site
Orange, California
Study site
Pittsburgh, Pennsylvania
Study site
San Diego, California
Study site
The Bronx, New York
Study site
Toledo, Ohio
Study site
Washington D.C., District of Columbia
Argentina4 sites
Study site
Buenos Aires
Study site
Córdoba
Study site
Loma Hermosa
Study site
Santa Fe
Brazil4 sites
Study site
Belo Horizonte
Study site
Caxias do Sul
Study site
Passo Fundo
Study site
São Paulo
Colombia4 sites
Study site
Bogotá
Study site
Cali
Study site
Floridablanca
Study site
Medellín
About this study
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
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.
Read the 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.
- Being tested
- Doripenem, Doripenem placebo, Cefepime, Cefepime placebo, Amoxicillin/clavulanate potassium
- Keywords
- Antibiotic, Child, Hospitalized, Complicated Urinary Tract Infection, Pyelonephritis, Doripenem, Cefepime
- Medical subject headings
- Pyelonephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoripenemDrug
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
Doripenem placeboDrug
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
CefepimeDrug
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
Cefepime placeboDrug
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
Amoxicillin/clavulanate potassiumDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Doripenem | Experimental | 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. Receives: Drug: Doripenem; Drug: Cefepime placebo; Drug: Amoxicillin/clavulanate potassium |
| Cefepime | Experimental | 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. Receives: Drug: Doripenem placebo; Drug: Cefepime; Drug: Amoxicillin/clavulanate potassium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: TOC (7 to 14 days after the last dose of study medication therapy)
Secondary outcomes (6)
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.
Measured: EIV (within 24 hours after completion of the last dose of IV study medication therapy)
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.
Measured: LFU (28 to 42 days after the last dose of study medication therapy)
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).
Measured: 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)
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).
Measured: EIV (within 24 hours after completion of the last dose of IV study medication therapy)
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).
Measured: TOC (7 to 14 days after the last dose of study medication therapy)
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).
Measured: LFU (28 to 42 days after the last dose of study medication therapy)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2010 (estimated)
- Study startDec 2010
- Primary completionJun 2013
- Study completionJun 2013
Why it stopped: Trial terminated early per business decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Complicated Urinary Tract Infections or PyelonephritisStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC C. Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01110408
- Sponsor's protocol ID
- CR016792
- Other IDs
- DORIPED3002, 2009-015953-18, 2009
- Status last verified
- Jul 2014
- First submitted
- 15 Apr 2010
- Last updated
- 15 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes