Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2008 Dec;122 Suppl 5(Suppl 5):S240-50.
doi: 10.1542/peds.2008-1285d.

Rationale and design issues of the Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) study

Ron Keren  1 , Myra A Carpenter, Alejandro Hoberman, Nader Shaikh, Tej K Matoo, Russell W Chesney, Ranjiv Matthews, Arlene C Gerson, Saul P Greenfield, Barbara Fivush, Gordon A McLurie, H Gil Rushton, Douglas Canning, Caleb P Nelson, Lawrence Greenbaum, Timothy Bukowski, William Primack, Richard Sutherland, James Hosking, Dawn Stewart, Jack Elder, Marva Moxey-Mims, Leroy Nyberg
Affiliations
Randomized Controlled Trial

Rationale and design issues of the Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) study

Ron Keren et al. Pediatrics. 2008 Dec.

Abstract

Objective: Our goal is to determine if antimicrobial prophylaxis with trimethoprim/sulfamethoxazole prevents recurrent urinary tract infections and renal scarring in children who are found to have vesicoureteral reflux after a first or second urinary tract infection.

Design, participants, and methods: The Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) study is a double-blind, randomized, placebo-controlled trial. Six hundred children aged 2 to 72 months will be recruited from both primary and subspecialty care settings at clinical trial centers throughout North America. Children who are found to have grades I to IV vesicoureteral reflux after the index febrile or symptomatic urinary tract infection will be randomly assigned to receive daily doses of either trimethoprim/sulfamethoxazole or placebo for 2 years. Scheduled follow-up contacts include in-person study visits every 6 months and telephone interviews every 2 months. Biospecimens (urine and blood) and genetic specimens (blood) will be collected for future studies of the genetic and biochemical determinants of vesicoureteral reflux, recurrent urinary tract infection, renal insufficiency, and renal scarring.

Results: The primary outcome is recurrence of urinary tract infection. Secondary outcomes include time to recurrent urinary tract infection, renal scarring (assessed by dimercaptosuccinic acid scan), treatment failure, renal function, resource utilization, and development of antimicrobial resistance in stool flora.

Conclusions: The RIVUR study will provide useful information to clinicians about the risks and benefits of prophylactic antibiotics for children who are diagnosed with vesicoureteral reflux after a first or second urinary tract infection. The data and specimens collected over the course of the study will allow researchers to better understand the pathophysiology of recurrent urinary tract infection and its sequelae.

Trial registration: ClinicalTrials.gov NCT00405704.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Flow diagram for recruitment and follow-up.
FIGURE 2
FIGURE 2
International Reflux Study VUR grading scheme.
FIGURE 3
FIGURE 3
Grading system for characterizing the extent of renal scarring: 0, no kidney segments affected; 1, 1 to 2 kidney segments affected; 2, 3 to 4 kidney segments affected; 3, >4 kidney segments affected; 4, global atrophy characterized by a diffusely scarred and shrunken kidney.
See this image and copyright information in PMC

References

    1. Schwab CW, Jr, Wu HY, Selman H, Smith GH, Snyder HM, 3rd, Canning DA. Spontaneous resolution of vesicoureteral reflux: a 15-year perspective. J Urol. 2002;168(6):2594–2599. - PubMed
    1. Smellie JM, Jodal U, Lax H, Möbius TT, Hirche H, Olbing H. Outcome at 10 years of severe vesicoureteric reflux managed medically: report of the International Reflux Study in Children. J Pediatr. 2001;139(5):656–663. - PubMed
    1. Greenfield SP, Ng M, Wan J. Resolution rates of low grade vesicoureteral reflux stratified by patient age at presentation. J Urol. 1997;157(4):1410–1413. - PubMed
    1. Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, Keren R. Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials. JAMA. 2007;298(2):179–186. - PubMed
    1. Kwok WY, de Kwaadsteniet MC, Harmsen M, van Suijlekom-Smit LW, Schellevis FG, van der Wouden JC. Incidence rates and management of urinary tract infections among children in Dutch general practice: results from a nation-wide registration study. BMC Pediatr. 2006;6:10. - PMC - PubMed

Publication types

MeSH terms

Substances

Associated data