Phase 3
N=607
Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)
Vesicoureteral Reflux · Urinary Tract Infections
Bottom Line
View on ClinicalTrials.gov: NCT00405704 ↗Enrolled (actual)
607
Serious AEs
0.0%
Results posted
Apr 2015
Primary outcome: Primary: Recurrent Febrile or Symptomatic Urinary Tract Infection During 2-year Follow-up — 39; 72 participants — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Trimethoprim-Sulfamethoxazole (Drug); Placebo (Drug)
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Primary completion
- Jun 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Recurrent Febrile or Symptomatic Urinary Tract Infection During 2-year Follow-up |
39; 72 | <0.001 sig |
| SECONDARY Outcome Renal Scarring |
27; 24 | 0.55 |
| SECONDARY Severe Renal Scarring on Outcome Scan |
9; 6 | 0.37 |
| SECONDARY New Renal Scarring on Outcome Scan |
18; 19 | 0.94 |
| SECONDARY Treatment Failure Composite |
14; 27 | 0.04 sig |
| SECONDARY Presence of E.Coli Resistant to Trimethoprim-Sulfamethoxazole (TMP-SMZ) (Based on Rectal Swab) |
56; 41 | 0.065 |
| SECONDARY Recurrent Febrile or Symptomatic UTI With Resistant E. Coli |
19; 11 | <0.001 sig |
| SECONDARY Recurrent Febrile or Symptomatic UTI With Any Resistant Pathogen |
26; 17 | <0.001 sig |
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
Data sourced from ClinicalTrials.gov (NCT00405704). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.