Cyclophosphamide Versus Mycophenolate Mofetil for the Treatment of Steroid-dependent Nephrotic Syndrome in Children

Idiopathic Nephrotic Syndrome Clinical Trial

— NEPHROMYCY  

Official title:

Cyclophosphamide Versus Mycophenolate Mofetil for Children With Steroid-dependent Idiopathic Nephrotic Syndrome : a Multicenter Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01092962
• Other study ID #: P071221
• Status: Completed
• Phase: Phase 3
• First received: February 26, 2010
• Last updated: March 25, 2015
• Start date: September 2010
• Est. completion date: February 2015

Study information

• Verified date: August 2013
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Idiopathic nephrotic syndrome is steroid-sensitive in more than 90% of cases in children. However 60% of cases are steroid dependent and required treatment with immunosuppressive agent. Cyclophosphamide and ciclosporin are used for long time to reduce steroid dependency, but duration of these treatments should be restricted because of gonadotoxicity for cyclophosphamide and nephrotoxicity for ciclosporin.

Mycophenolate mofetil appears as an alternative treatment without gonadotoxicity and nephrotoxicity. However, contrary to cyclophosphamide, mycophenolate mofetil does not seem to have a residual action so that treatment must be maintained during months or years.

The aim of the study is to compare efficacy of cyclophosphamide and mycophenolate mofetil in steroid dependent nephrotic syndrome in children.

Description:

Aim of the study: Comparison of efficacy of cyclophosphamide 148mg/kg in 12 weeks and mycophenolate mofetil 1200mg/m² during 18 months, in children with steroid dependent nephrotic syndrome.

The 70 patients will be recruited in the 26 centres of paediatric nephrology in France, included and randomized at the time of a relapse. They will receive the same steroid treatment in the 2 arms.

The primary point will be occurrence of a relapse during the 24 months of follow-up. Detection of relapse will be done by using dipsticks and confirm by biological dosages (albuminemia and proteinuria/CREATININURIA ratio). Clinical and biological check up will be done every 3 months during all the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 16 Years

Eligibility

Inclusion Criteria:

• children 2 to 16 years old

• steroid dependency =30mg/m² eod

• or steroid dependency =15mg/m² eod and occurrence of : at least 2 relapses in 1 year, adverse event of steroid therapy (height rate =-1SD, obesity, other complication) or severe complication of nephrotic syndrome (thrombosis, collapse, severe infection,…)

• inform consent

Exclusion Criteria:

• steroid resistant nephrotic syndrome

• prior treatment with cyclophosphamide, mycophenolate mofetil or cyclosporine

• absence of contraception in pubescent girls

• allergy to cyclophosphamide or mycophenolate mofetil

• malignant disease

• treatment with other immunosuppressant treatment or with non-steroid anti-inflammatory or anti proteinuric medication (enzyme converse antagonist and angiotensin II receptor antagonist)

• absence of inform consent

• participation to other therapeutic trial

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Idiopathic Nephrotic Syndrome
• Nephrosis
• Nephrosis, Lipoid
• Nephrotic Syndrome
• Syndrome

Intervention

Drug:
• Cyclophosphamide
2mg/kg/day during 12 weeks (cumulative dose 148mg/kg)
• Mycophenolate mofetil
1200mg/m²/jour in two divided doses during 18 months

Locations

Country	Name	City	State
France	Robert Debre Hospital, AP-HP	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse of nephrotic syndrome (defined by occurrence of proteinuria = 0,25 g/mmol of CREATININURIA (or = 2g/g) with hypoalbuminemia = 30g/L AND/OR dipsticks >2+ during 3 days and proteinuria/CREATININURIA ratio = 0,25 g/mmol) during 2 years.		Months 1, 3, 6, 9, 12, 15, 18, 21, 24	Yes
Secondary	In case of relapse, steroid threshold dose to maintain a remission compare to those before inclusion in the study		Months 1, 3, 6, 9, 12, 15, 18, 21, 24	Yes
Secondary	Cumulative steroid dose received during the years before and under treatment		Months 1, 3, 6, 9, 12, 15, 18, 21, 24	Yes
Secondary	Comparison of growth data, during the year before and under treatment		Months 1, 3, 6, 9, 12, 15, 18, 21, 24	Yes
Secondary	Pharmacokinetics measurement of MPA and relation with efficacy in case of treatment with MMF		One month after beginning MMF	Yes