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

Overview

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.

Full Title of Study: “Cyclophosphamide Versus Mycophenolate Mofetil for Children With Steroid-dependent Idiopathic Nephrotic Syndrome : a Multicenter Randomized Controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 2015

Detailed 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.

Interventions

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

Arms, Groups and Cohorts

  • Experimental: Mycophenolate mofetil
    • Mycophenolate mofetil
  • Active Comparator: Cyclophosphamide
    • Cumulative dose of 148mg/kg of cyclophosphamide in 84 days (2mg/kg/day during 12 weeks)

Clinical Trial Outcome Measures

Primary Measures

  • 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.
    • Time Frame: Months 1, 3, 6, 9, 12, 15, 18, 21, 24

Secondary Measures

  • In case of relapse, steroid threshold dose to maintain a remission compare to those before inclusion in the study
    • Time Frame: Months 1, 3, 6, 9, 12, 15, 18, 21, 24
  • Cumulative steroid dose received during the years before and under treatment
    • Time Frame: Months 1, 3, 6, 9, 12, 15, 18, 21, 24
  • Comparison of growth data, during the year before and under treatment
    • Time Frame: Months 1, 3, 6, 9, 12, 15, 18, 21, 24
  • Pharmacokinetics measurement of MPA and relation with efficacy in case of treatment with MMF
    • Time Frame: One month after beginning MMF

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 2 Years

Maximum Age: 16 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Assistance Publique – Hôpitaux de Paris
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Véronique BAUDOUIN, MD, Principal Investigator, Assistance Publique – Hôpitaux de Paris

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