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

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

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Nephrotic Syndrome
• Intervention / Treatment: Drug: Mycophenolate mofetil; Drug: Cyclophosphamide

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75019
    • Robert Debré Hospital, AP-HP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mycophenolate mofetil	Drug: Mycophenolate mofetil; 1200mg/m²/jour in two divided doses during 18 months; Other Names: Cellcept (Roche)
Active Comparator: Cyclophosphamide; Cumulative dose of 148mg/kg of cyclophosphamide in 84 days (2mg/kg/day during 12 weeks)	Drug: Cyclophosphamide; 2mg/kg/day during 12 weeks (cumulative dose 148mg/kg); Other Names: Endoxan (BAXTER)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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
Cumulative steroid dose received during the years before and under treatment	Months 1, 3, 6, 9, 12, 15, 18, 21, 24
Comparison of growth data, during the year before and under treatment	Months 1, 3, 6, 9, 12, 15, 18, 21, 24
Pharmacokinetics measurement of MPA and relation with efficacy in case of treatment with MMF	One month after beginning MMF

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Véronique BAUDOUIN, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: February 26, 2010
• First Submitted That Met QC Criteria: March 24, 2010
• First Posted (Estimate): March 25, 2010

Study Record Updates

• Last Update Posted (Estimate): March 26, 2015
• Last Update Submitted That Met QC Criteria: March 25, 2015
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Children; Cyclophosphamide; Mycophenolate mofetil; Idiopathic nephrotic steroid sensitive syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Syndrome; Nephrotic Syndrome; Nephrosis; Nephrosis, Lipoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Cyclophosphamide; Mycophenolic Acid
• Other Study ID Numbers: P071221