Trial record 1 of 1 for:    RIVUR
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Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00405704
First received: November 29, 2006
Last updated: March 19, 2014
Last verified: March 2014
  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 3

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:


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 ]

Enrollment: 607
Study Start Date: May 2007
Estimated Study Completion Date: April 2014
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Trimethoprim-Sulfamethoxazole 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: Placebo 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Hide Study Locations
Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35233
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Illinois
Ann & Robert Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60614
United States, Maryland
Johns Hopkins School of Medicine
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Children's Hospital of Boston
Boston, Massachusetts, United States, 02115
United States, Michigan
Children's Hospital of Michigan
Detroit, Michigan, United States, 48201
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, New York
Women and Children's Hospital of Buffalo
Buffalo, New York, United States, 14222
United States, North Carolina
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Akron Children's Hospital
Akron, Ohio, United States, 44308
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin Children's Hospital
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
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 Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
Principal Investigator: Milan Nadkarni, MD 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:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00405704     History of Changes
Other Study ID Numbers: DK074059 (IND), U01 DK074059
Study First Received: November 29, 2006
Last Updated: March 19, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

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 July 22, 2014