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

Phase 3
Completed
Conditions
Idiopathic Nephrotic Syndrome
Interventions
Registration Number
NCT01092962
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
Brief 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
70
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Mycophenolate mofetilMycophenolate mofetilMycophenolate mofetil
CyclophosphamideCyclophosphamideCumulative dose of 148mg/kg of cyclophosphamide in 84 days (2mg/kg/day during 12 weeks)
Primary Outcome Measures
NameTimeMethod
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
Secondary Outcome Measures
NameTimeMethod
In case of relapse, steroid threshold dose to maintain a remission compare to those before inclusion in the studyMonths 1, 3, 6, 9, 12, 15, 18, 21, 24
Cumulative steroid dose received during the years before and under treatmentMonths 1, 3, 6, 9, 12, 15, 18, 21, 24
Comparison of growth data, during the year before and under treatmentMonths 1, 3, 6, 9, 12, 15, 18, 21, 24
Pharmacokinetics measurement of MPA and relation with efficacy in case of treatment with MMFOne month after beginning MMF

Trial Locations

Locations (1)

Robert Debre Hospital, AP-HP

🇫🇷

Paris, France

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