Steroid Sensitive Nephrotic Syndrome in Children

Nephrotic Syndrome in Children Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03878914
• Other study ID #: 1901002013
• Status: Terminated
• Phase: Phase 4
• Start date: August 6, 2019
• Est. completion date: October 31, 2021

Study information

• Verified date: April 2022
• Source: Wayne State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: October 31, 2021
• Est. primary completion date: October 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypersensitivity
• Nephrosis
• Nephrotic Syndrome
• Nephrotic Syndrome in Children
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
China	Children's Hospital of Fudan University	Shanghai
United States	Wayne Pediatrics	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Wayne State University	Children's Hospital of Fudan University

Countries where clinical trial is conducted

United States,  China, 

References & Publications (15)

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. — View Citation

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. — View Citation

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. — View Citation

Elzouki AY, Amin F, Jaiswal OP. Primary nephrotic syndrome in Arab children. Arch Dis Child. 1984 Mar;59(3):253-5. — View Citation

Hahn D, Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2015 Mar 18;(3):CD001533. doi: 10.1002/14651858.CD001533.pub5. Review. — View Citation

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. — View Citation

Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001533. Review. Update in: Cochrane Database Syst Rev. 2015;3:CD001533. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Sharples PM, Poulton J, White RH. Steroid responsive nephrotic syndrome is more common in Asians. Arch Dis Child. 1985 Nov;60(11):1014-7. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of relapses	Number of relapses per patient after completion of treatment.	52 weeks
Secondary	Number of frequent relapses	Number of frequent relapses per patient after completion of treatment.	52 weeks
Secondary	Number of patients with steroid dependence	Number of patients who show steroid dependence after completion of treatment.	52 weeks
Secondary	Number of patients with late steroid resistance	Number of patients who show late steroid resistance after completion of treatment.	52 weeks
Secondary	Cumulative steroid dose in two groups	The total dose of corticosteroids received in Group A patients versus Group B patients	60 to 64 weeks
Secondary	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
Secondary	Weight profile	Weight profile in Group A patients versus Group B patients	60-64 weeks
Secondary	Height Profile	Height profile in Group A patients versus Group B patients	60-64 weeks