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


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.
Keren
Ron
R
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. keren@email.chop.edu
Carpenter
Myra A
MA
Hoberman
Alejandro
A
Shaikh
Nader
N
Matoo
Tej K
TK
Chesney
Russell W
RW
Matthews
Ranjiv
R
Gerson
Arlene C
AC
Greenfield
Saul P
SP
Fivush
Barbara
B
McLurie
Gordon A
GA
Rushton
H Gil
HG
Canning
Douglas
D
Nelson
Caleb P
CP
Greenbaum
Lawrence
L
Bukowski
Timothy
T
Primack
William
W
Sutherland
Richard
R
Hosking
James
J
Stewart
Dawn
D
Elder
Jack
J
Moxey-Mims
Marva
M
Nyberg
Leroy
L
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002921:Cicatrix / Q000209:etiology / Q000517:prevention & control; D002985:Clinical Protocols; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D011704:Pyelonephritis / Q000473:pathology / Q000517:prevention & control; D012008:Recurrence; D012107:Research Design; D014463:Ultrasonography; D019564:Unnecessary Procedures; D014552:Urinary Tract Infections / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D014718:Vesico-Ureteral Reflux / Q000150:complications*
D000900:Anti-Bacterial Agents