Reduced-dose steroid treatment for children with nephrotic syndrome

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

This study is testing if giving kids with nephrotic syndrome a lower dose of steroids can help them recover from relapses just as well as the usual higher dose.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 1 Year to 18 Years
• Sex: All
• Sponsor: The Hospital for Sick Children (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT06635720 on ClinicalTrials.gov

What this trial studies

This pilot feasibility study aims to evaluate the effectiveness and safety of a reduced-dose oral prednisone regimen for treating relapses of childhood steroid-sensitive nephrotic syndrome compared to the standard-dose regimen. Conducted at The Hospital for Sick Children in Toronto, Canada, this single-center, open-label randomized controlled trial will assess the feasibility and resources needed for a larger multi-center trial. Children aged 1-18 years diagnosed with idiopathic nephrotic syndrome and experiencing a relapse will be included, while those with certain exclusions will not be eligible. The study will monitor participants' responses to the different steroid dosages without requiring additional laboratory tests to facilitate recruitment.

Who should consider this trial

Good fit: Ideal candidates are children aged 1-18 years diagnosed with idiopathic nephrotic syndrome who are currently experiencing a relapse.

Not a fit: Patients who have received more than two days of standard-dose prednisone or have severe complications such as acute kidney injury will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to a safer and more effective treatment regimen for children with nephrotic syndrome, potentially reducing steroid exposure.

How similar studies have performed: While this approach is being tested in this pilot study, similar studies have shown promise in evaluating reduced steroid regimens for various conditions, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

1. Provide informed consent ± assent
2. Participant age 1-18 years
3. 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)
4. Active nephrotic syndrome relapse at time of enrolment (defined as recurrence of nephrotic-range proteinuria \[≥3+ protein on dipstick for ≥3 consecutive days18 OR first morning or 24-hour urine protein/creatinine ratio ≥200mg/mmol AND ≥1+ protein on dipstick for ≥3 consecutive days\])
5. Ability to take oral medication and willingness to adhere to either study prednisone regimen
6. Ability and willingness to adhere to home urine and symptom monitoring during the initial two-week period after assigned treatment initiation
7. Have not been previously included in the RESPONSE trial
8. Participant located in Ontario, Canada at the time of study enrolment

Exclusion Criteria:

1. Prednisone treatment (at any dose) for the active relapse episode for \>2-days prior to study enrolment
2. Relapse episode within the past 6-weeks (i.e., date of relapse onset within 6-weeks prior to date of enrolment)
3. Current receipt of high-dose maintenance prednisone therapy (dose \>0.6mg/kg on alternate days or \>0.3mg/kg daily)
4. 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)
5. Congenital or monogenic cause of nephrotic syndrome (defined as age at diagnosis \<1-year or known/suspected monogenic cause of nephrotic syndrome)
6. 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)
7. Presence of moderate-to-severe peripheral edema (grade 3+; indentation depth ≥5mm and rebound time \>15 seconds)
8. Hospitalization since the onset of the active relapse episode
9. Acute kidney injury (KDIGO stage ≥1) since the onset of the active relapse episode
10. Active or prior known or suspected venous thromboembolism during a relapse episode
11. Active pregnancy or lactation
12. 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

Where this trial is running

Toronto, Ontario

• The Hospital for Sick Children — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Rulan Parekh, MD MS — The Hospital for Sick Children
• Study coordinator: Cal Robinson, MBChB

Conditions Nephrotic Syndrome in Children; Nephrotic Syndrome, Minimal Change; Nephrotic Syndrome; Nephrotic Syndrome，Idiopathic; Nephrotic syndrome; Idiopathic nephrotic syndrome; Childhood nephrotic syndrome; Minimal change disease