Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 607
- 试验地点
- 19
- 主要终点
- Recurrent Febrile or Symptomatic Urinary Tract Infection During 2-year Follow-up
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Months 至 71 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Trimethoprim-Sulfamethoxazole
Cherry-flavored liquid suspension with 3 mg of trimethoprim plus 15 mg sulfamethoxazole per kilogram of body weight, taken once daily.
干预措施: Trimethoprim-Sulfamethoxazole (Drug)
Placebo
Cherry-flavored liquid suspension matched to active comparator.
干预措施: Placebo (Drug)
结局指标
主要结局
Recurrent Febrile or Symptomatic Urinary Tract Infection During 2-year Follow-up
时间窗: 2 years
次要结局
- Outcome Renal Scarring(2 years)
- Severe Renal Scarring on Outcome Scan(2 years)
- New Renal Scarring on Outcome Scan(2 years)
- Treatment Failure Composite(2 years)
- Presence of E.Coli Resistant to Trimethoprim-Sulfamethoxazole (TMP-SMZ) (Based on Rectal Swab)(2 years)
- Recurrent Febrile or Symptomatic UTI With Resistant E. Coli(2 years)
- Recurrent Febrile or Symptomatic UTI With Any Resistant Pathogen(2 years)