NCT00405704COMPLETEDResults postedPhase 3In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infecton, we evaluated the efficacy of Trimethoprim-Sulfamethoxazole (TMP-SMZ) prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance.
Inclusion Criteria: * Age at randomization: at least 2 months, but less than 6 years of age. Note that children as young as 1 month were screened for the study. * Diagnosed first or second febrile or symptomatic UTI within 112 days prior to randomization * Presence of Grade I- IV VUR based on radiographic voiding cystourethrogram (VCUG) performed within 112 days of diagnosis of index UTI. * Appropriately treated index febrile or symptomatic UTI Exclusion Criteria: * Index UTI diagnosis more than 112 days prior to randomization * History of more than two UTIs prior to randomization * For patients less than 6 months of age at randomization, gestational age less than 34 weeks * Co-morbid urologic anomalies * Hydronephrosis, SFU Grade 4 * Ureterocele * Urethral valve * Solitary kidney * Profoundly decreased renal size unilaterally on ultrasound (based on 2 standard deviations below the mean for age and length) performed within 112 days after diagnosis of index UTI * Multicystic dysplastic kidney * Neurogenic bladder * Pelvic kidney or fused kidney * Known sulfa allergy, inadequate renal or hepatic function, Glucose-6-phosphate dehydrogenase deficiency or other conditions that are contraindications for use of TMP-SMZ * History of other renal injury/disease * Unable to complete the study protocol * Congenital or acquired immunodeficiency * Underlying anomalies or chronic diseases that could potentially interfere with response to therapy such as chronic gastrointestinal conditions (i.e., malabsorption, inflammatory bowel disease), liver or kidney failure, or malignancy. * Complex cardiac disease as defined in the Manual of Procedures. * Any known syndromes associated with VUR or bladder dysfunction * Index UTI not successfully treated * Unlikely to complete follow-up * Family history of anaphylactic reaction to sulfa medications