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

NCT06635720 | Recruiting Phase 3 DMC

• 1 other identifier: 1000081679
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Nephrotic syndrome; Idiopathic nephrotic syndrome; Childhood nephrotic syndrome; Minimal change disease; Focal segmental glomerulosclerosis

Outcome Measures

Primary Outcomes (1)

• Study recruitment rate

  Number of participants enrolled per study month

  1 year

Secondary Outcomes (10)

• Treatment effect - treatment failure

  From enrolment to 2-week study visit

• Number of eligible participants

  1 year

• Number of participants that initiate assigned treatment

  1 year

• Participant drop-out rate

  1 year

• Treatment preference

  1 year

Study Arms (2)

Reduced-dose steroids

EXPERIMENTAL

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.

Drug: Prednisone

Standard-dose steroids

ACTIVE COMPARATOR

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.

Drug: Prednisone

Interventions

Prednisone DRUG

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.

Also known as: Prednisolone

Reduced-dose steroids; Standard-dose steroids

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Hospital for Sick Children: lead

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5G 1E8, Canada

RECRUITING

MeSH Terms

Conditions

Nephrosis, Lipoid; Nephrotic Syndrome; Glomerulosclerosis, Focal Segmental

Interventions

Prednisone; Prednisolone

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis; Nephritis

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols

Study Officials

• Rulan Parekh, MD MS

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cal Robinson, MBChB

CONTACT

416-813-5807; cal.robinson@sickkids.ca

Jovanka Vasilevska-Ristovska

CONTACT

416-813-7654; jovanka.vasilevska-ristovska@sickkids.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff physician, clinician-scientist

Study Record Dates

• First Submitted: September 30, 2024
• First Posted: October 10, 2024
• Study Start: November 1, 2024
• Primary Completion: November 30, 2025
• Study Completion (Estimated): November 30, 2026
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)