Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) - Full Text View

Sponsor:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00405704

Purpose

The purpose of this study is to learn whether children with vesicoureteral reflux (VUR) grades I - IV 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.

Condition	Intervention	Phase
Vesico-Ureteral Reflux Urinary Tract Infections	Drug: Trimethoprim-Sulfamethoxazole Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics Fever GERD Scars Urinary Tract Infections

Drug Information available for: Sulfamethoxazole Trimethoprim Trimethoprim-sulfamethoxazole combination

U.S. FDA Resources

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:

Recurrent febrile or symptomatic urinary tract infection during 2-year follow-up [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Renal scarring based on DMSA scan performed 1 and 2 years after enrollment [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Severe renal scarring on outcome scan [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Presence of E.coli resistant to TMP/SMZ (based on rectal swab) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Recurrent febrile or symptomatic UTI caused by TMP/SMZ-resistant organism [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	600
Study Start Date:	May 2007
Estimated Study Completion Date:	October 2013
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1	Drug: Trimethoprim-Sulfamethoxazole Cherry-flavored liquid suspension in which each 5 mL contains 200 mg sulfamethoxazole and 40 mg trimethoprim. Prophylactic dose is based on trimethoprim component: 3 mg per kg body weight taken once daily. Other Names: Sulfatrim Bactrim
Placebo Comparator: 2	Drug: Placebo Cherry flavored liquid suspension matched to active comparator.

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. 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%. The primary analysis is intention-to-treat with missing outcome data analyzed as UTI.

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.

Eligibility

Ages Eligible for Study:	2 Months to 71 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00405704

Show 19 Study Locations

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Principal Investigator:	Sahar Fathallah, MD	University of Alabama, Birmingham, AL
Principal Investigator:	Myra A Carpenter, PhD	University of NC at Chapel Hill, Chapel Hill, NC
Principal Investigator:	Caleb P. Nelson, MD, MPH	Children's Hospital of Boston, Boston, MA
Principal Investigator:	Eileen Brewer, MD	Texas Children's Hospital, Houston, TX
Principal Investigator:	Saul P Greenfield, MD	Women and Children's Hospital of Buffalo, Buffalo, NY
Principal Investigator:	Alejandro Hoberman, MD	Children's Hospital of Pittsburgh, Pittsburgh, PA
Principal Investigator:	Ron Keren, MD, MPH	Children's Hospital of Philadelphia, Philadelphia, PA
Principal Investigator:	Bradley P Kropp, MD	University of Oklahoma, Oklahoma City, OK
Principal Investigator:	Ranjiv Mathews, MD	Johns Hopkins University
Principal Investigator:	Tej K Mattoo, MD,DCH, FRCP	Wayne State University School of Medicine, Detroit, MI
Principal Investigator:	H. Gil Rushton, MD, FAAP	Children's Research Institute
Principal Investigator:	Mary Ann Queen, MD	Children's Mercy Hospital-Kansas City, MO
Study Chair:	Russell W Chesney, MD	Le Bonheur Children's Medical Center, Memphis, TN
Principal Investigator:	Steven J Skoog, MD FACS,FAAP	Oregon Health & Science University, Portland, OR
Principal Investigator:	Amy Renwick, MD	Alfred I. duPont Hospital for Children, Wilmington, DE
Principal Investigator:	Earl Y. Cheng, MD	Children's Memorial Hospital, Chicago, IL
Principal Investigator:	Gordon McLorie, MD,FAAP,FRCSC	Wake Forest University Baptist Medical Center, Winston-Salem, NC
Principal Investigator:	Caleb P Nelson, MD, MPH	Children's Hospital of Boston, Boston, MA
Principal Investigator:	William R DeFoor, Jr, MD, MPH	Cincinnati Children's Hospital, Cincinnati, OH
Principal Investigator:	Dan McMahon, MD	Akron Children's Hospital, Akron, OH
Principal Investigator:	Ross Decter, MD	Penn State Hershey Medical Center, Hershey, PA
Principal Investigator:	Sharon M Bartosh, MD	University of Wisconsin, Madison

More Information

Additional Information:

RIVUR trial web site This link exits the ClinicalTrials.gov site

No publications provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Keren R, Carpenter MA, Hoberman A, Shaikh N, Matoo TK, Chesney RW, Matthews R, Gerson AC, Greenfield SP, Fivush B, McLurie GA, Rushton HG, Canning D, Nelson CP, Greenbaum L, Bukowski T, Primack W, Sutherland R, Hosking J, Stewart D, Elder J, Moxey-Mims M, Nyberg L. Rationale and design issues of the Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) study. Pediatrics. 2008 Dec;122 Suppl 5:S240-50.

Responsible Party:	Marva Moxey-Mims, MD, Project Officer, NIDDK
ClinicalTrials.gov Identifier:	NCT00405704 History of Changes
Other Study ID Numbers:	DK074059 (IND), U01 DK074059
Study First Received:	November 29, 2006
Last Updated:	April 25, 2011
Health Authority:	United States: Federal Government; United States: Food and Drug Administration; United States: Institutional Review Board; Canada: Health Canada

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

Vesico-Ureteral Reflux
Urinary Tract Infections
Renal Scarring
Antibiotic Resistance

Controlled Clinical Trial
Trimethoprim-Sulfamethoxazole
Children

Additional relevant MeSH terms:

Gastroesophageal Reflux
Urinary Tract Infections
Vesico-Ureteral Reflux
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Infection
Urologic Diseases
Urinary Bladder Diseases
Sulfamethoxazole
Trimethoprim

Trimethoprim-Sulfamethoxazole Combination
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012