NCT06635720

REduced-dose Steroid PrOtocol for Childhood Nephrotic SyndromE (RESPONSE)

REduced-dose Steroid PrOtocol for Childhood Nephrotic SyndromE (RESPONSE): a Pilot Open-label Randomized, Controlled Trial

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: The Hospital for Sick Children · Academic / Other
• Sex: All
• Age: 1 Year – 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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: Reduced-dose steroids (intervention): oral prednisone 30mg/m2 (1mg/kg; max 40mg) daily until remission, then 20mg/m2 (0.66mg/kg; max 25mg) on alternate days for four weeks. Standard-dose steroids (control): oral prednisone 60mg/m2 (2mg/kg; max 60mg) daily until remission, then 40mg/m2 (1.5mg/kg; max 50mg) on alternate days for four weeks. Randomization 1:1 using permuted blocks. If a participant does not achieve remission by 2-weeks, develops symptomatic edema, stage 2+ acute kidney injury, or thromboembolism, they will be escalated to standard-dose steroids. Outcomes: The primary outcome is recruitment rate (number enrolled per month), since it is the greatest anticipated barrier to RCT feasibility. Other feasibility, tolerability, and safety outcomes are listed in Table 1. The pilot study will test case report forms, data management, quality control, and training systems. We will estimate treatment effect for the full-scale RCT's primary outcome (complete remission without steroid dose escalation by 2-weeks), to re-estimate sample size and evaluate full-scale RCT feasibility. Sample size: For this pilot study, we will recruit 50 children (25 per arm), which is 15% of the estimated sample size of the full-scale RCT. Sample size for this pilot must be adequate to assess RCT feasibility.

Conditions

• Nephrotic Syndrome in Children
• Nephrotic Syndrome, Minimal Change
• Nephrotic Syndrome
• Nephrotic Syndrome，Idiopathic

Interventions

Type	Name	Description
DRUG	Prednisone	This study will compare two steroid dosing protocols for the treatment of childhood nephrotic syndrome relapses. The medications used for both intervention and control arms are oral prednisone 5mg tablets (DIN: 00312770) for children able to swallow or use crushed tablets, or oral prednisolone sodium phosphate 5mg base/5mL liquid (DIN: 02245532). Participants hospitalized after study enrollment will be permitted to switch to intravenous methylprednisolone sodium succinate (DIN: 02367955) at the same dose without being considered to have violated their treatment assignment.

Timeline

• Start date: 2024-11-01
• Primary completion: 2025-11-30
• Completion: 2026-11-30
• First posted: 2024-10-10
• Last updated: 2025-03-11

Locations

1 site across 1 country: Canada