Steroid Sensitive Nephrotic Syndrome in Children

Study Overview
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Brief Summary
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Idiopathic nephrotic syndrome (INS) is one of the most common glomerular pathologies in children and corticosteroid therapy is its most effective treatment. The total duration of treatment ranges anywhere from two to six months, generally about 3 months. The main objective of our study is to test the feasibility of a shorter total duration (two months) of corticosteroid therapy in patients who show a quicker treatment response to the initial treatment.

Detailed Description
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Idiopathic nephrotic syndrome (INS) is one of the most common glomerular pathologies in children and corticosteroid therapy is its most effective treatment. The main objective of our prospective, open-label, observational clinical cohort study is to test the feasibility of a shorter duration of corticosteroid therapy in patients who show a quicker treatment response. We hypothesize that the clinical outcomes in children with time to remission of ≤10 days and treated with only 8 weeks of corticosteroid therapy will not be significantly different as compared to those with time to remission of >10 days and treated with ≥12 weeks of standard corticosteroid therapy. Our specific aims are as follows: First, we will evaluate the time to first relapse after 8-week corticosteroid therapy in quick responders in comparison to the standard treatment of ≥12 weeks in slow responders. Second, we will assess the frequency of relapses during one year follow-up after completion of 8-week corticosteroid therapy in quick responders in comparison to the standard treatment of ≥12 weeks in slow responders. To complete the study successfully during the funding period of two years and to increase the generalizability of its results, the study will recruit 66 patients at six study participating sites in five countries, including U.S., India, China, Egypt, and Qatar. The sites have been carefully selected on the basis of their reputation, patient volume, research experience, and PI's personal rapport with the site investigators. The proposed study is innovative because it seeks a paradigm shift from 'one-size-fits-all' to an entirely new concept of individualized treatment duration based on time to remission with initial corticosteroid therapy. The proposed study is the first precision medicine initiative in the management of INS. The project is significant because of the potential to improve public health by decreasing the side effects of prolonged corticosteroid administration in about half of the patients diagnosed with INS. Our long-term objective is to develop additional novel therapeutic strategies to optimize the use of corticosteroids in the management of initial episode and relapses in children with INS.

Official Title
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A Multinational Prospective Study on the Duration of Steroid Therapy in Steroid Sensitive Nephrotic Syndrome

Conditions
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Nephrotic Syndrome in Children

Intervention / Treatment
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* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 1 to <19 years Newly diagnosed INS Patient in remission with steroids Written informed consent/Assent for the study OR as required by the local IRB Exclusion Criteria: Age < 1 year or ≥ 19 years Uncertainty about patient/parent adherence. Abnormal serum creatinine for patient age Steroid resistant nephrotic syndrome Any co-morbid condition that might require modification in treatment with steroids.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Patients will be divided into two groups based on time to remission with initial standard dose of corticosteroids. Patients who respond within 10 days (Group A) will receive a total of 8 weeks of corticosteroid therapy whereas those who respond between 10 days to 28 days (Group B) will receive ≥12 weeks ((maximum of 16 weeks) of corticosteroid therapy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quick responders (Group A)<br>Patients will be divided into two groups based on time to remission with initial standard dose of corticosteroids. Patients who respond within 10 days (Group A) will receive a total of 8 weeks of corticosteroid therapy whereas those who respond between 10 days to 28 days (Group B) will receive ≥12 weeks ((maximum of 16 weeks) of corticosteroid therapy. CORTICOSTEROID THERAPY FOR INITIAL EPISODE Group A (Total duration of therapy 8 weeks) 60mg/m2/day or 2mg/kg/day (maximum 60mg) day for 2 weeks 40mg/m2 or 1.5mg (maximum 40mg) every other day for 2 weeks. Wean off in 4 weeks CORTICOSTEROID THERAPY FOR A RELAPSE 60mg/m2/day or 2mg/kg/day (maximum 60mg) until remission 40mg/m2 or 1.5mg (maximum 40mg) every other day for one week followed by continued weaning until discontinued in 6-8 weeks. | Drug: Corticosteroids<br>* Patients will be divided into two groups based on time to remission with initial standard dose of corticosteroids. Patients who respond within 10 days (Group A) will receive a total of 8 weeks of corticosteroid therapy whereas those who respond between 10 days to 28 days (Group B) will receive ≥12 weeks ((maximum of 16 weeks) of corticosteroid therapy.<br>|
| Active Comparator: Slow responders (Group B)<br>CORTICOSTEROID THERAPY FOR INITIAL EPISODE Group B: (Total duration of therapy ≥ 12 weeks) 60mg/m2/day or 2mg/kg/day (maximum 60mg) day for 4 weeks 40mg/m2 or 1.5mg (maximum 40mg) every other day for 4 weeks. Wean off in 4-6 weeks CORTICOSTEROID THERAPY FOR A RELAPSE 60mg/m2/day or 2mg/kg/day (maximum 60mg) until remission 40mg/m2 or 1.5mg (maximum 40mg) every other day for one week followed by continued weaning until discontinued in 6-8 weeks. | Drug: Corticosteroids<br>* Patients will be divided into two groups based on time to remission with initial standard dose of corticosteroids. Patients who respond within 10 days (Group A) will receive a total of 8 weeks of corticosteroid therapy whereas those who respond between 10 days to 28 days (Group B) will receive ≥12 weeks ((maximum of 16 weeks) of corticosteroid therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first relapse. | The study will evaluate the time in weeks for patients to relapse after completion of initial treatment and if there is any difference between Group A and Group B. | 60-64 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of relapses | Number of relapses per patient after completion of treatment. | 52 weeks | 
| Number of frequent relapses | Number of frequent relapses per patient after completion of treatment. | 52 weeks | 
| Number of patients with steroid dependence | Number of patients who show steroid dependence after completion of treatment. | 52 weeks | 
| Number of patients with late steroid resistance | Number of patients who show late steroid resistance after completion of treatment. | 52 weeks | 
| Cumulative steroid dose in two groups | The total dose of corticosteroids received in Group A patients versus Group B patients | 60 to 64 weeks | 
| Number of episodes of upper respiratory infection (URI) and other infections. | The total number of URI or other infections in Group A patients versus Group B patients after completion of treatment. | 52-weeks | 
| Weight profile | Weight profile in Group A patients versus Group B patients | 60-64 weeks | 
| Height Profile | Height profile in Group A patients versus Group B patients | 60-64 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nephrotic sydrome, Steroid sensitive nephrotic syndrome