REduced-dose Steroid PrOtocol for Childhood Nephrotic SyndromE (RESPONSE): a Pilot Open-label Randomized, Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Study recruitment rate
研究概览
简要总结
This is a pilot feasibility study for a proposed full-scale randomized controlled trial to evaluate the effectiveness and safety of a reduced-dose oral prednisone (steroids) regimen to treat childhood steroid-sensitive nephrotic syndrome relapses versus standard-dose prednisone (i.e., usual standard of care).
This internal pilot study is a single-center, open-label, randomized controlled trial at The Hospital for Sick Children (Toronto, ON, Canada). The primary objective of this pilot study is to determine the feasibility, safety, and resources needed to conduct the future full-scale randomized controlled trial.
详细描述
Study design:
This is a pilot study for a planned multi-center, Bayesian adaptive, non-inferiority RCT (Figure 1). This planned multi-center RCT will require additional funding, which we will apply for if feasibility is shown by this pilot. This pilot is a single-center (SickKids) open-label RCT comparing reduced vs. standard-dose steroids to treat nephrotic syndrome relapses.
Study population:
We will include children (1-18 years) from Ontario, Canada that are diagnosed with idiopathic SSNS and present in relapse (≥3+ dipstick protein or protein:creatinine ratio ≥200mg /mmol for ≥3 consecutive days). We will exclude children that have received >2 days of standard-dose prednisone; are on maintenance high-dose prednisone (>0.3mg/kg per day or >0.6mg/kg alternate days); have relapsed within the past 6 weeks; have grade 3+ peripheral edema (i.e., moderate-severe); are hospitalized; have stage 2+ acute kidney injury; or have thromboembolism. Children receiving other steroid-sparing immunosuppressives are eligible, but target drug levels will remain constant until the 2-week visit. No additional laboratory or imaging tests are needed, to maximize recruitment.
Interventions:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide informed consent ± assent
- •Participant age 1-18 years
- •Diagnosis of idiopathic nephrotic syndrome (defined as nephrotic-range proteinuria [first morning or 24-hour urine protein/creatinine ratio ≥200mg/mmol or ≥3+ protein on dipstick] and either hypoalbuminemia [serum albumin <30g/L] or edema)
- •Active nephrotic syndrome relapse at time of enrolment (defined as recurrence of nephrotic-range proteinuria [≥3+ protein on dipstick for ≥3 consecutive days18 OR first morning or 24-hour urine protein/creatinine ratio ≥200mg/mmol AND ≥1+ protein on dipstick for ≥3 consecutive days])
- •Ability to take oral medication and willingness to adhere to either study prednisone regimen
- •Ability and willingness to adhere to home urine and symptom monitoring during the initial two-week period after assigned treatment initiation
- •Have not been previously included in the RESPONSE trial
- •Participant located in Ontario, Canada at the time of study enrolment
排除标准
- •Prednisone treatment (at any dose) for the active relapse episode for >2-days prior to study enrolment
- •Relapse episode within the past 6-weeks (i.e., date of relapse onset within 6-weeks prior to date of enrolment)
- •Current receipt of high-dose maintenance prednisone therapy (dose >0.6mg/kg on alternate days or >0.3mg/kg daily)
- •Steroid-resistant nephrotic syndrome classification (defined as lack of complete remission within 6-weeks after initiating daily steroid treatment at a standard dose for the initial episode of nephrotic syndrome)
- •Congenital or monogenic cause of nephrotic syndrome (defined as age at diagnosis <1-year or known/suspected monogenic cause of nephrotic syndrome)
- •Secondary cause of nephrotic syndrome (includes membranous nephropathy, post-infectious glomerulonephritis [GN], complement-mediated GN [e.g., C3 glomerulopathy and immune complex-GN], IgA nephropathy, IgA vasculitis, lupus nephritis, medication-induced nephrotic syndrome, malignancy-induced nephrotic syndrome, active hepatitis B or C infection, or active HIV infection)
- •Presence of moderate-to-severe peripheral edema (grade 3+; indentation depth ≥5mm and rebound time >15 seconds)
- •Hospitalization since the onset of the active relapse episode
- •Acute kidney injury (KDIGO stage ≥1) since the onset of the active relapse episode
- •Active or prior known or suspected venous thromboembolism during a relapse episode
- •Active pregnancy or lactation
- •Any condition or diagnosis, that could in the opinion of the Principal Investigator or delegate interfere with the participant's ability to comply with study instructions, might confound the interpretation of the study results, or put the participant at risk
研究组 & 干预措施
Standard-dose steroids
Standard-dose steroid protocol (control): oral prednisone or prednisolone 60mg/m2 (2mg/kg; max 60mg) daily until remission, then 40mg/m2 (1.5mg/kg; max 50mg) on alternate days for four weeks.
干预措施: Prednisone (Drug)
Reduced-dose steroids
Reduced-dose steroid protocol (intervention): oral prednisone or prednisolone 30mg/m2 (1mg/kg; max 40mg) daily until remission, then 20mg/m2 (0.66mg/kg; max 25mg) on alternate days for four weeks.
干预措施: Prednisone (Drug)
结局指标
主要结局
Study recruitment rate
时间窗: 1 year
Number of participants enrolled per study month
次要结局
- Number of participants that initiate assigned treatment(1 year)
- Treatment effect - treatment failure(From enrolment to 2-week study visit)
- Number of eligible participants(1 year)
- Participant drop-out rate(1 year)
- Treatment preference(1 year)
- Hospitalizations(From enrolment to 1 year)
- Cumulative steroid dose(From enrolment to 1 year)
- Adverse events(From enrolment to 1 year)
- Treatment adherence(From enrolment to 1 year)
- Number of participants that complete 2-week study visit(2 weeks)
研究者
Rulan Parekh
Staff physician, clinician-scientist
The Hospital for Sick Children