title: Rationale and design issues of the Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) study.
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.
  
  
  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.
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. keren@email.chop.edu
authors.forename: Ron
authors.initials: R
authors.lastname: Keren
authors.forename: Myra A
authors.initials: MA
authors.lastname: Carpenter
authors.forename: Alejandro
authors.initials: A
authors.lastname: Hoberman
authors.forename: Nader
authors.initials: N
authors.lastname: Shaikh
authors.forename: Tej K
authors.initials: TK
authors.lastname: Matoo
authors.forename: Russell W
authors.initials: RW
authors.lastname: Chesney
authors.forename: Ranjiv
authors.initials: R
authors.lastname: Matthews
authors.forename: Arlene C
authors.initials: AC
authors.lastname: Gerson
authors.forename: Saul P
authors.initials: SP
authors.lastname: Greenfield
authors.forename: Barbara
authors.initials: B
authors.lastname: Fivush
authors.forename: Gordon A
authors.initials: GA
authors.lastname: McLurie
authors.forename: H Gil
authors.initials: HG
authors.lastname: Rushton
authors.forename: Douglas
authors.initials: D
authors.lastname: Canning
authors.forename: Caleb P
authors.initials: CP
authors.lastname: Nelson
authors.forename: Lawrence
authors.initials: L
authors.lastname: Greenbaum
authors.forename: Timothy
authors.initials: T
authors.lastname: Bukowski
authors.forename: William
authors.initials: W
authors.lastname: Primack
authors.forename: Richard
authors.initials: R
authors.lastname: Sutherland
authors.forename: James
authors.initials: J
authors.lastname: Hosking
authors.forename: Dawn
authors.initials: D
authors.lastname: Stewart
authors.forename: Jack
authors.initials: J
authors.lastname: Elder
authors.forename: Marva
authors.initials: M
authors.lastname: Moxey-Mims
authors.forename: Leroy
authors.initials: L
authors.lastname: Nyberg
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents