Randomized Intervention for Children With Vesicouretera...

Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)

Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)

Sponsored by: 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 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.

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

MedlinePlus related topics: Antibiotics Fever Scars Urinary Tract Infections

Drug Information available for: Sulfamethoxazole Trimethoprim Trimethoprim-sulfamethoxazole combination

U.S. FDA Resources

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

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

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 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
1: Active Comparator 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.
2: Placebo Comparator 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) 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.

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

Locations


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

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

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

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

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

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

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

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

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

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

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

United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Hilary S. Turner, MPH 267-426-5683 turnerh@email.chop.edu
Principal Investigator: Ron Keren, MD, MPH
Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Diana Kearney, RN 412-692-6717 diana.kearney@chp.edu
Principal Investigator: Alejandro Hoberman, MD

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