Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)

Condition(s) targeted: Vesico-Ureteral Reflux; Urinary Tract Infections

Intervention: Trimethoprim-Sulfamethoxazole (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Official(s) and/or principal investigator(s):
Mark Benfield, MD, Principal Investigator, Affiliation: University of Alabama, Birmingham, AL
Myra A Carpenter, PhD, Principal Investigator, Affiliation: University of NC at Chapel Hill, Chapel Hill, NC
Ghaleb Daouk, MD, Principal Investigator, Affiliation: Children's Hospital of Boston, Boston, MA
Stuart Goldstein, MD, Principal Investigator, Affiliation: Texas Children's Hospital, Houston, TX
Saul P Greenfield, MD, Principal Investigator, Affiliation: Women and Children's Hospital of Buffalo, Buffalo, NY
Alejandro Hoberman, MD, Principal Investigator, Affiliation: Children's Hospital of Pittsburgh, Pittsburgh, PA
Ron Keren, MD, MPH, Principal Investigator, Affiliation: Children's Hospital of Philadelphia, Philadelphia, PA
Bradley P Kropp, MD, Principal Investigator, Affiliation: University of Oklahoma, Oklahoma City, OK
Ranjiv Mathews, MD, Principal Investigator, Affiliation: Johns Hopkins University
Tej K Mattoo, MD,DCH, FRCP, Principal Investigator, Affiliation: Wayne State University School of Medicine, Detroit, MI
H. Gil Rushton, MD, FAAP, Principal Investigator, Affiliation: Children's National Medical Center, Washington, DC
Uri Alon, MD, Principal Investigator, Affiliation: Children's Mercy Hospital-Kansas City, MO
Russell W Chesney, MD, Study Chair, Affiliation: Le Bonheur Children's Medical Center, Memphis, TN
Steven J Skoog, MD FACS,FAAP, Principal Investigator, Affiliation: Oregon Health and Science University
Julie Barthold, MD, Principal Investigator, Affiliation: Alfred I. duPont Hospital for Children, Wilmington, DE
Earl Y. Cheng, MD, Principal Investigator, Affiliation: Children's Memorial Hospital, Chicago, IL
Gordon McLorie, MD,FAAP,FRCSC, Principal Investigator, Affiliation: Wake Forest University Baptist Medical Center, Winston-Salem, NC
Caleb P Nelson, MD, MPH, Principal Investigator, Affiliation: Children's Hospital of Boston, Boston, MA
William R DeFoor, Jr, MD, MPH, Principal Investigator, Affiliation: Cincinnati Children's Hospital, Cincinnati, OH
Dan McMahon, MD, Principal Investigator, Affiliation: Akron Children's Hospital, Akron, OH
Ross Decter, MD, Principal Investigator, Affiliation: Penn State Hershey Medical Center, Hershey, PA
Sharon M Bartosh, MD, Principal Investigator, Affiliation: University of Wisconsin, Madison

The purpose of this study is to learn whether all children with vesicoureteral reflux (VUR) should be treated with antibiotics. The study will tell us if prophylactic antibiotic treatment prevents urinary tract infections and renal scarring in children with VUR.

Official title: Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)

Study design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Recurrent febrile or symptomatic urinary tract infection during 2-year follow-up

Secondary outcome:

Renal scarring based on DMSA scan performed 1 and 2 years after enrollment

Severe renal scarring on outcome scan

Treatment failure composite based on multiple recurrent UTIs or, in children with baseline scarring of grade 3 or higher, new renal scarring at 12-months or further scarring at any time following recurrent febrile UTI

Presence of E.coli resistant to TMP/SMZ (based on rectal swab)

Recurrent febrile or symptomatic UTI caused by TMP/SMZ-resistant organism

Detailed description: This multicenter, randomized, double-blind, placebo-controlled trial is designed to determine whether daily antimicrobial prophylaxis is superior to placebo in preventing recurrence of urinary tract infection (UTI) in children with vesicoureteral reflux (VUR). Eligibility criteria are described elsewhere. Patients will be randomly assigned to treatment for 2 years with daily antimicrobial prophylaxis (trimethoprim-sulfamethoxazole) or placebo. The study is designed to recruit 600 children (approximately 300 in each treatment group) over a 24 month period. The protocol will encourage prompt evaluation of children with UTI symptoms and early therapy of culture-proven UTIs. It is expected that approximately 10% of children will have to discontinue study medication due to allergic reactions. Assuming a 20% placebo event rate and 10% non-compliance rate, the study has 83% power to detect an absolute 10% event rate in the antimicrobial prophylaxis group. If the placebo event rate is instead 25%, power is 97% to detect an absolute 10% event rate in the treated group, even if non-compliance is as high as 15%.

In addition to collecting follow-up data on urinary tract infections, renal scarring and antimicrobial resistance, quality of life, compliance, safety parameters, utilization of health resources, and change in VUR will be assessed periodically throughout the study.

Minimum age: 2 Months. Maximum age: 71 Months. Gender(s): Both.

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 may be 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 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, G6PD 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

University of Alabama, Birmingham, Alabama 35233, United States; Recruiting
Michelle Sharbono, RN,BSN,CCRC, Phone: 205-558-2792, Email: Michelle.Sharbono@chsys.org
Mark Benfield, MD, Principal Investigator

Alfred I. duPont Hospital for Children, Wilmington, Delaware 19803, United States; Recruiting
Coralee Karmazyn, RN, BSN, CCRP, Phone: (302) 651-4542, Email: ckarmazy@nemours.org
Julie Barthold, MD, Principal Investigator

Children's National Medical Center, Washington, District of Columbia 20010, United States; Recruiting
Bruce M Sprague, BS, Phone: 202-884-3433, Email: bsprague@cnmc.org
H. Gil Rushton, MD, FAAP, Principal Investigator

Children's Memorial Hospital, Chicago, Illinois 60614, United States; Recruiting
Theresa Meyer, MS, RN, CPN, Phone: 773-880-3528, Email: tmeyer@childrensmemorial.org
Earl Y Cheng, MD, Principal Investigator

Johns Hopkins School of Medicine, Baltimore, Maryland 21287, United States; Recruiting
Buffy Garrett, RN, Phone: 410-200-1609, Email: bgarret4@jhmi.edu
Ranjiv Mathews, MD, Principal Investigator

Children's Hospital of Boston, Boston, Massachusetts 02115, United States; Recruiting
Ilina Rosoklija, Phone: 617-355-4720, Email: Ilina.rosoklija@childrens.harvard.edu
Ghaleb Daouk, MD, Principal Investigator
Caleb Nelson, MD, Principal Investigator

Children's Hospital of Michigan, Detroit, Michigan 48201, United States; Recruiting
Lena Peschansky, RN, BSN, Phone: 313-745-5604, Email: lpeschan@med.wayne.edu
Tej K Mattoo, MD,DCH,FRCP, Principal Investigator

Children's Mercy Hospital, Kansas City, Missouri 64108, United States; Recruiting
Janelle Jennings, RN, Phone: 816-983-6966, Email: jjennings@cmh.edu
Uri Alon, MD, Principal Investigator

Women and Children's Hospital of Buffalo, Buffalo, New York 14222, United States; Recruiting
Allyson J Fried, CPNP, Phone: 716-878-7306, Email: afried@kaleidahealth.org
Saul P Greenfield, MD, Principal Investigator

Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina 27157, United States; Recruiting
Michelle Treadwell, Phone: 336-716-4084, Email: mtreatwe@wfubmc.edu
Gordon McLorie, MD, FAAP,FRCSC, Principal Investigator

Cincinnati Children's Hospital, Cincinnati, Ohio 45229, United States; Recruiting
Julie Denlinger, Phone: 513-636-6273, Email: Julie.Denlinger@cchmc.org
William R DeFoor, Jr, MD, MPH, Principal Investigator

Akron Children's Hospital, Akron, Ohio 44308, United States; Recruiting
Ruthie Youssefi, Phone: 330-543-8628, Email: ryoussefi@chmca.org
Dan McMahon, MD, Principal Investigator

University of Oklahoma, Oklahoma City, Oklahoma 73104, United States; Recruiting
Kirk B Wettengel, Phone: 405-271-6900, Ext: 46260, Email: kirk-wettengel@ouhsc.edu
Bradley P Kropp, MD, Principal Investigator

Oregon Health & Science University, Portland, Oregon 97239, United States; Recruiting
Jenifer Borruel Rector, RN, BSN, Phone: 503-494-7187, Email: borruelr@ohsu.edu
Steven J Skoog, MD FACS,FAAP, Principal Investigator

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Recruiting
Hilary S. Turner, MPH, Phone: 267-426-5683, Email: turnerh@email.chop.edu
Ron Keren, MD, MPH, Principal Investigator

Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States; Recruiting
Diana Kearney, RN, Phone: 412-692-6717, Email: diana.kearney@chp.edu
Alejandro Hoberman, MD, Principal Investigator

Penn State Hershey Medical Center, Hershey, Pennsylvania 17033, United States; Recruiting
Susan Worley, RN, BSN, Phone: 717-531-5718, Email: sworley@psu.edu
Ross Decter, MD, Principal Investigator

Texas Children's Hospital, Houston, Texas 77030, United States; Recruiting
Beth Soletsky, RN, BSN, Phone: 832-824-3789, Email: lodinger@bcm.tmc.edu
Stuart Goldstein, MD, Principal Investigator

University of Wisconsin Children's Hospital, Madison, Wisconsin 53792, United States; Not yet recruiting
Stacey C Moyer, Phone: 608-262-9531, Email: scmoyer@pediatrics.wisc.edu
Lori Wollet, Phone: 608-262-6855, Email: lw3@clinicaltrials.wisc.edu
Sharon M Bartosh, MC, Principal Investigator

RIVUR trial web site

Starting date: May 2007
Ending date: October 2011
Last updated: May 20, 2009