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

This study has been completed.
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: April 15, 2015
Last verified: April 2015

November 29, 2006
April 15, 2015
May 2007
June 2013   (final data collection date for primary outcome measure)
Recurrent Febrile or Symptomatic Urinary Tract Infection During 2-year Follow-up [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Recurrent febrile or symptomatic urinary tract infection during 2-year follow-up
Complete list of historical versions of study NCT00405704 on ClinicalTrials.gov Archive Site
  • Outcome Renal Scarring [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Renal scarring was defined as a decreased uptake of tracer that was associated with loss of contours or the presence of cortical thinning. Outcome dimercaptosuccinic acid (DMSA) scan was performed at 2 years after enrollment or 3-4 months after the child had met treatment failure criteria.
  • Severe Renal Scarring on Outcome Scan [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Severe renal scarring was defined as scarring in more than 4 of 12 segments in at least one kidney or global atrophy characterized by diffusely scarred and shrunken kidney. Outcome DMSA scan performed at 2 years after enrollment or 3-4 months after the child had met treatment failure criteria.
  • New Renal Scarring on Outcome Scan [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    New renal scarring was defined as scarring on the outcome renal scan with technetium -99m-labeled dimercaptosuccinic acid that was not present at baseline. Outcome DMSA scan performed at 2 years after enrollment or 3-4 months after the child had met treatment failure criteria.
  • Treatment Failure Composite [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Treatment failure was defined as the occurrence of two febrile urinary tract infections (UTIs), one febrile UTI and three symptomatic UTIs, four symptomatic UTIs, or new or worsening renal scarring on an interim scan (e.g,, the 12-month visit); renal scans from the 2-year visit are NOT considered in the treatment failure criteria.
  • Presence of E.Coli Resistant to Trimethoprim-Sulfamethoxazole (TMP-SMZ) (Based on Rectal Swab) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Recurrent Febrile or Symptomatic UTI With Resistant E. Coli [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Recurrent Febrile or Symptomatic UTI With Any Resistant Pathogen [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • 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
Not Provided
Not Provided
 
Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)
Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)

In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infecton, we evaluated the efficacy of Trimethoprim-Sulfamethoxazole (TMP-SMZ) prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance.

This multicenter, randomized, double-blind, placebo-controlled trial was 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 were randomly assigned to treatment for 2 years with daily antimicrobial prophylaxis (trimethoprim-sulfamethoxazole) or placebo. The study was designed to recruit 600 children (approximately 300 in each treatment group). The protocol encouraged prompt evaluation of children with UTI symptoms and early therapy of culture-proven UTIs. It was 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 were assessed periodically throughout the study.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Vesicoureteral Reflux
  • Urinary Tract Infections
  • Drug: Trimethoprim-Sulfamethoxazole
    Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.
    Other Names:
    • Sulfatrim
    • Bactrim
  • Drug: Placebo
    Cherry flavored liquid suspension matched to active comparator.
  • Active Comparator: Trimethoprim-Sulfamethoxazole
    Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.
    Intervention: Drug: Trimethoprim-Sulfamethoxazole
  • Placebo Comparator: Placebo
    Cherry-flavored liquid suspension matched to active comparator.
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
607
May 2014
June 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age at randomization: at least 2 months, but less than 6 years of age. Note that children as young as 1 month were 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 voiding cystourethrogram (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, Glucose-6-phosphate dehydrogenase 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
Both
2 Months to 71 Months
No
Contact information is only displayed when the study is recruiting subjects
United States
Canada
 
NCT00405704
DK074059 (IND), U01 DK074059
Yes
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Not Provided
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
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP