Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)
Condition: Vesicoureteral Reflux; Urinary Tract Infections
MeSH terms: Urinary Tract Infections; Gastroesophageal Reflux; Vesico-Ureteral Reflux
Intervention: Trimethoprim-Sulfamethoxazole; Placebo
Intervention description: Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.; Cherry flavored liquid suspension matched to active comparator.
Intervention MeSH terms: Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Sulfamethoxazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 607.0
Sex: All
Minimum age: 2 Months
Maximum age: 71 Months
Healthy volunteers: No
Keywords: Vesicoureteral Reflux; Urinary Tract Infections; Renal Scarring; Antibiotic Resistance; Controlled Clinical Trial; Trimethoprim-Sulfamethoxazole; Children

Summary:

      In 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.
    

Eligibility criteria:

        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