Steroid Sensitive Nephrotic Syndrome in Children

NCT03878914 | Terminated Phase 4 FDA Drug

• 1 other identifier: 1901002013
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Nephrotic Syndrome in Children

Keywords

Nephrotic sydrome; Steroid sensitive nephrotic syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Number of relapses

  52 weeks

• Number of frequent relapses

  52 weeks

• Number of patients with steroid dependence

  52 weeks

• Number of patients with late steroid resistance

  52 weeks

• Cumulative steroid dose in two groups

  60 to 64 weeks

Study Arms (2)

Quick responders (Group A)

EXPERIMENTAL

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

Slow responders (Group B)

ACTIVE COMPARATOR

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

Interventions

Corticosteroids DRUG

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.

Quick responders (Group A); Slow responders (Group B)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wayne State University: lead
• Children's Hospital of Fudan University: collaborator

Study Sites (2)

Wayne Pediatrics

Detroit, Michigan, 48201, United States

Location

Children's Hospital of Fudan University

Shanghai, 201102, China

Location

Related Publications (16)

• 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.

  PMID: 25785660 BACKGROUND

• 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.

  PMID: 17943754 BACKGROUND

• 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.

  PMID: 25054775 BACKGROUND

• 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.

  PMID: 25029428 BACKGROUND

• 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.

  PMID: 23052648 BACKGROUND

• 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.

  PMID: 20223477 BACKGROUND

• 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.

  PMID: 10699098 BACKGROUND

• 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.

  PMID: 18618150 BACKGROUND

• 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.

  PMID: 973 BACKGROUND

• 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.

  PMID: 6712274 BACKGROUND

• 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.

  PMID: 4073933 BACKGROUND

• Banh THM, 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 CPB, 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.

  PMID: 27445165 BACKGROUND

• 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.

  PMID: 2242321 BACKGROUND

• 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.

  PMID: 10603129 BACKGROUND

• 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.

  PMID: 12776266 BACKGROUND

• Tang X, Shen Q, Rao J, Chen J, Fang X, Zhang Z, Grewal M, Mattoo T, Xu H. Duration of initial prednisolone therapy for first episode of childhood nephrotic syndrome based on time to response. Front Pediatr. 2022 Nov 2;10:1043285. doi: 10.3389/fped.2022.1043285. eCollection 2022.

  PMID: 36405821 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome

Interventions

Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Tej Mattoo, MD

  Wayne State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: March 18, 2019
• Study Start: August 6, 2019
• Primary Completion: October 31, 2021
• Study Completion: October 31, 2021
• Last Updated: May 2, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CN (1)