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

• Conditions: Complicated Urinary Tract Infections; MedDRA version: 14.0Level: PTClassification code 10046571Term: Urinary tract infectionSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2009-015953-18-LV
• Lead Sponsor: Janssen-Cilag International NV, Turnhoutseweg 30, 2340 Beerse, Belgium

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11-24
• Last Update Posted: 16 September 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

1- Have evidence of pyuria as demonstrated by either of the following:
o A urine specimen that is positive for leukocyte esterase via urine dipstick or urinalysis
o A urine specimen with =10 WBCs per microliter from an unspun sample or =5 WBCs per high power field from a centrifuged specimen.
2- Have a current documented or suspected cUTI or pyelonephritis as indicated by the following clinical signs or symptoms:
COMPLICATED URINARY TRACT INFECTION
o Symptomatic cUTI
Children 3 months to <2 years of age
Must have at least ONE of the following signs or symptoms:
– Vomiting
– Recent weight loss or failure to thrive
– Abdominal pain
– Irritability
– Poor feeding
– Decrease in normal level of activity
AND
– have at least ONE complicating factor (see below)
Children 2 to <18 years of age
Must have at least ONE of the following signs or symptoms:
– Dysuria
– Increased urinary frequency
– Urgency
– Suprapubic or abdominal pain
– Secondary urinary incontinence
AND
– have at least ONE complicating factor (see below)
o Asymptomatic cUTI
Children 3 months to <18 years of age
Must be unable to perceive symptoms of UTI due to congenital or acquired spinal cord injury or abnormality
AND
have at least ONE complicating factor (see below)
Complicating Factors for All Age Categories (3 months to <18 years of age): All subjects enrolled with a diagnosis of complicated UTI must have at least ONE of the following complicating factors:
- Indwelling urinary catheter or other indwelling urinary tract instrumentation that is anticipated to be removed during the course of IV study drug therapy
- Use of intermittent urinary catheterization
- Urogenital surgery within the 7 days before administration of the first dose of IV study drug
- Known functional or anatomic abnormality of the urogenital tract
- Obstructive uropathy where the obstruction is likely to resolve or be relieved during the course of IV study drug therapy administration
- Previously documented vesicoureteral reflux
- Neurogenic disturbances of micturition with significant impact on bladder emptying with bladder residual volume =50 mL for children weighing <40 kg and =100 mL for children weighing =40 kg as previously determined by voiding cystourethrogram (VCUG) or ultrasound or urinary catheterization immediately post void. (Chang 2009)
- Recurrent UTI (defined as 2 or more previous UTIs within a 12-month period)
- Evidence that the current UTI may be caused by a resistant uropathogen including a suspected breakthrough infection in a child receiving chronic antimicrobial prophylaxis for the prevention of UTI
- Prior documentation of congenital structural or functional urologic
abnormality including but not limited to findings from prenatal or postnatal ultrasound or postnatal VCUG
PYELONEPHRITIS
Subjects in all age categories (3 months to <18 years of age) enrolled with a diagnosis of pyelonephritis must have both:
Evidence of systemic inflammatory response as demonstrated by at least ONE of the following:
o Fever (oral temperature >38.0C, tympanic temperature >38.3C, or rectal or core temperature >38.8C) or hypothermia (rectal or core temperature <35.0C)
o Have leukocytosis defined as WBC >or=15,000 cells/microL OR >or=15% immature neutrophils, regardless of the total peripheral white cell count
AND
Have at least ONE of the following signs or symptoms:
Children 3 months to <2 years of age
– Vomiting
– Recent weight loss or failure to thrive
– A

Exclusion Criteria

1 - Have a history of hypersensitivity reactions to carbapenems, cephalosporins, penicillins, or other beta-lactam antibiotics. Note: Subjects with a history of mild non-urticarial skin rash temporally related to but considered not associated with the previous use of beta-lactam antibiotics are permitted to enroll in the study. For such subjects, there must be a description of the rash and documentation by the investigator that upon review of the history it is his/her opinion that the rash was unlikely due to any of the above-mentioned classes of drugs for the subject to qualify for inclusion in the study.
2 - Concomitant infection including but not limited to suspected or confirmed meningitis or other central nervous system infection requiring systemic antibiotic or antifungal therapy at the time of randomization. (Clarification: possible bacteremia with the presumed same urinary pathogen is acceptable).
3 - Received any amount systemic antibiotic therapy within 96 hours (4 days) before obtaining the pretreatment baseline urine culture specimen. (Exception: Subjects receiving oral antibiotics for UTI prophylaxis and are suspected to have a breakthrough UTI are eligible to enroll if all other eligibility criteria are met including obtaining a baseline urine culture specimen).
4 - Have received more than 24 hours of systemic antibiotic therapy after obtaining the pretreatment baseline urine culture specimen
5 - Girls who are pregnant or are nursing a child or are menarchal, and, if sexually active, are not practicing a highly effective method of birth control (eg, prescription hormonal contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method, eg, condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel, male partner sterilization) as local regulations permit, before screening and do not agree to continue using a highly effective method of birth control (as previously described) for 30 days after administration of the last dose of study drug therapy. Note: for all menarchal girls, confirm a negative urine or serum pregnancy test (beta-human chorionic gonadotropin [beta-hCG]) at screening, before enrolling the subject into the study.
6 - Have a history of uncontrolled epilepsy defined as at least 1 seizure within the 6 months before randomization

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified