Steroid Sensitive Nephrotic Syndrome in Children

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

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.

Study Overview

• Status: Terminated
• Conditions: Nephrotic Syndrome in Children
• Intervention / Treatment: Drug: Corticosteroids

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 201102
    • Children's Hospital of Fudan University
• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne Pediatrics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Quick responders (Group A); 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; 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.
ACTIVE_COMPARATOR: Slow responders (Group B); 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Wayne State University
• Collaborators: Children's Hospital of Fudan University
• Investigators: Principal Investigator: Tej Mattoo, MD, Wayne State University

Publications and helpful links

General Publications

• Hahn D, Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2015 Mar 18;2015(3):CD001533. doi: 10.1002/14651858.CD001533.pub5.
• Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001533. doi: 10.1002/14651858.CD001533.pub4.
• Yoshikawa N, Nakanishi K, Sako M, Oba MS, Mori R, Ota E, Ishikura K, Hataya H, Honda M, Ito S, Shima Y, Kaito H, Nozu K, Nakamura H, Igarashi T, Ohashi Y, Iijima K; Japanese Study Group of Kidney Disease in Children. A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment. Kidney Int. 2015 Jan;87(1):225-32. doi: 10.1038/ki.2014.260. Epub 2014 Jul 23.
• Sinha A, Saha A, Kumar M, Sharma S, Afzal K, Mehta A, Kalaivani M, Hari P, Bagga A. Extending initial prednisolone treatment in a randomized control trial from 3 to 6 months did not significantly influence the course of illness in children with steroid-sensitive nephrotic syndrome. Kidney Int. 2015 Jan;87(1):217-24. doi: 10.1038/ki.2014.240. Epub 2014 Jul 16.
• Lombel RM, Hodson EM, Gipson DS; Kidney Disease: Improving Global Outcomes. Treatment of steroid-resistant nephrotic syndrome in children: new guidelines from KDIGO. Pediatr Nephrol. 2013 Mar;28(3):409-14. doi: 10.1007/s00467-012-2304-8. Epub 2012 Oct 5.
• Vivarelli M, Moscaritolo E, Tsalkidis A, Massella L, Emma F. Time for initial response to steroids is a major prognostic factor in idiopathic nephrotic syndrome. J Pediatr. 2010 Jun;156(6):965-971. doi: 10.1016/j.jpeds.2009.12.020. Epub 2010 Mar 10.
• Constantinescu AR, Shah HB, Foote EF, Weiss LS. Predicting first-year relapses in children with nephrotic syndrome. Pediatrics. 2000 Mar;105(3 Pt 1):492-5. doi: 10.1542/peds.105.3.492.
• Letavernier B, Letavernier E, Leroy S, Baudet-Bonneville V, Bensman A, Ulinski T. Prediction of high-degree steroid dependency in pediatric idiopathic nephrotic syndrome. Pediatr Nephrol. 2008 Dec;23(12):2221-6. doi: 10.1007/s00467-008-0914-y. Epub 2008 Jul 11.
• Srivastava RN, Mayekar G, Anand R, Choudhry VP, Ghai OP, Tandon HD. Nephrotic syndrome in indian children. Arch Dis Child. 1975 Aug;50(8):626-30. doi: 10.1136/adc.50.8.626.
• Elzouki AY, Amin F, Jaiswal OP. Primary nephrotic syndrome in Arab children. Arch Dis Child. 1984 Mar;59(3):253-5. doi: 10.1136/adc.59.3.253.
• Sharples PM, Poulton J, White RH. Steroid responsive nephrotic syndrome is more common in Asians. Arch Dis Child. 1985 Nov;60(11):1014-7. doi: 10.1136/adc.60.11.1014.
• Banh TH, Hussain-Shamsy N, Patel V, Vasilevska-Ristovska J, Borges K, Sibbald C, Lipszyc D, Brooke J, Geary D, Langlois V, Reddon M, Pearl R, Levin L, Piekut M, Licht CP, Radhakrishnan S, Aitken-Menezes K, Harvey E, Hebert D, Piscione TD, Parekh RS. Ethnic Differences in Incidence and Outcomes of Childhood Nephrotic Syndrome. Clin J Am Soc Nephrol. 2016 Oct 7;11(10):1760-1768. doi: 10.2215/CJN.00380116. Epub 2016 Jul 21.
• Mattoo TK, Mahmood MA, al-Harbi MS. Nephrotic syndrome in Saudi children clinicopathological study of 150 cases. Pediatr Nephrol. 1990 Sep;4(5):517-9. doi: 10.1007/BF00869837.
• Bagga A, Hari P, Srivastava RN. Prolonged versus standard prednisolone therapy for initial episode of nephrotic syndrome. Pediatr Nephrol. 1999 Nov;13(9):824-7. doi: 10.1007/s004670050708.
• Hiraoka M, Tsukahara H, Matsubara K, Tsurusawa M, Takeda N, Haruki S, Hayashi S, Ohta K, Momoi T, Ohshima Y, Suganuma N, Mayumi M; West Japan Cooperative Study Group of Kidney Disease in Children. A randomized study of two long-course prednisolone regimens for nephrotic syndrome in children. Am J Kidney Dis. 2003 Jun;41(6):1155-62. doi: 10.1016/s0272-6386(03)00346-9.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 6, 2019
• Primary Completion (ACTUAL): October 31, 2021
• Study Completion (ACTUAL): October 31, 2021

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (ACTUAL): March 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Steroid sensitive nephrotic syndrome; Nephrotic sydrome
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Kidney Diseases; Urologic Diseases; Disease; Hypersensitivity; Syndrome; Nephrotic Syndrome; Nephrosis
• Other Study ID Numbers: 1901002013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Depending on available resources, we may share data without any patient identifier with the study site investigators as well as others who might be interested.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No