Evaluation of Low Dose Corticosteroids Efficiency, Associated With Myfortic ® in the Treatment of Nephrotic Syndrome (MSN)

Low Steroid Dose Combined With Mycophenolic Acid (Myfortic) Compared With High Dose Steroid for Minimal Change Nephrotic Syndrome

A multicenter, randomized, study will be performed to evaluate the efficacy of low dose steroid combined with mycophenolic acid (MyforticR) versus high dose steroid in inducing remission in adults with minimal change nephrotic syndrome (MCNS). One hundred and fourteen patients (CPP decision 2009-04-02-a5) will be included in this study. They will be randomly assigned to an open label treatment with either prednisone

1 mg/kg/day (arm A) or 0,5 mg/kg/day plus myforticR 1440 mg/day (arm B) for four weeks. The outcome will be compared during one-year follow up

Study Overview

• Status: Completed
• Conditions: Nephrotic Syndrome
• Intervention / Treatment: Drug: acid mycophenolic (Myfortic); Drug: Prednisone

Detailed Description

The treatment for minimal change nephrotic syndrome (MCNS) is empirically based on high dose steroid. However, the side effects in adult patients are often significant and induce a lot of complications. This prospective study aimed to compare low dose steroid combined with mycophenolic acid (MyforticR) versus high dose steroid in the treatment of the first episode of MCNS.

Treatment Plan

After baseline evaluation including clinical biological and histological analyses, all eligible patients will be an open label assigned to two groups:

Group A: patients will receive prednisone 1 mg/kg/day for 4 weeks. Then, the dose will be progressively tapered if the remission will be achieved. For patients who exhibit incomplete remission at this time, high dose steroid will be continued for 4 weeks again before the tapering.

Group B: patients will receive prednisone 0.5 mg/kg/day combined with mycophenolic acid (MyforticR) 1440 mg/day. The management of steroid therapy will be identical in both groups, while MyforticR will be continued for six months.

In both groups, patients who will not achieve remission after 8 weeks of steroid therapy at full dose will be excluded from the study.

Statistical Analysis In this multicenter, randomized trial, the primary and secondary end points will be the rate of complete remission within 4 and 8 weeks of the start of induction therapy, respectively.

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Val de Marne
    • Creteil, Val de Marne, France, 94010
      • Henri Mondor Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Idiopathic nephrotic syndrome
• Flare of idiopathic syndrome without treatment from one year
• Confirming by Renal Biopsy

Exclusion Criteria:

• Secondary nephrotic syndrome
• Pregnancy
• Focal Segmental Glomerular sclerosis lesion in the Biopsy
• Neutropenia < 2000/mm3
• Hb<9gr/dl

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: B-Experimental; Experimental	Drug: acid mycophenolic (Myfortic); patients will receive prednisone 0.5 mg/kg/day combined with mycophenolic acid (MyforticR) 1440 mg/day. The management of steroid therapy will be identical in both groups, while MyforticR will be continued for six months; Other Names: Bitherapy: Association of low dose corticosteroids 0.5 mg/kg/day and Myfortic ® at a dose of 1440 mg/day.
Active Comparator: A-Active Comparator; Active Comparator	Drug: Prednisone; 1 mg/kg/day for 4 weeks. Then, the dose will be progressively tapered if the remission will be achieved. For patients who exhibit incomplete remission at this time, high dose steroid will be continued for 4 weeks again before the tapering.; Other Names: Monotherapy: treatment with only corticosteroids at doses usually 1 mg/kg/day,following a plan of reduction based on the degree of remission.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete remission	complete remission	within 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete remission	complete remission	within 8 weeks
partial remission	partial remission	within 4 and 8 weeks
Adverse effects in both arms	Adverse effects in both arms	1 year
Number of flare in both arms	Number of flare in both arms	at 1 year

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Novartis
• Investigators: Principal Investigator: Philippe REMY, MD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Azukaitis K, Palmer SC, Strippoli GF, Hodson EM. Interventions for minimal change disease in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2022 Mar 1;3(3):CD001537. doi: 10.1002/14651858.CD001537.pub5.
• Remy P, Audard V, Natella PA, Pelle G, Dussol B, Leray-Moragues H, Vigneau C, Bouachi K, Dantal J, Vrigneaud L, Karras A, Pourcine F, Gatault P, Grimbert P, Ait Sahlia N, Moktefi A, Daugas E, Rigothier C, Bastuji-Garin S, Sahali D; MSN Trial Investigators. An open-label randomized controlled trial of low-dose corticosteroid plus enteric-coated mycophenolate sodium versus standard corticosteroid treatment for minimal change nephrotic syndrome in adults (MSN Study). Kidney Int. 2018 Dec;94(6):1217-1226. doi: 10.1016/j.kint.2018.07.021. Epub 2018 Oct 29.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: September 7, 2010
• First Submitted That Met QC Criteria: September 8, 2010
• First Posted (Estimate): September 9, 2010

Study Record Updates

• Last Update Posted (Actual): June 28, 2017
• Last Update Submitted That Met QC Criteria: June 27, 2017
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Myfortic; Minimal Change Disease; Complete remission; Minimal Change Nephrotic Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Syndrome; Nephrotic Syndrome; Nephrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Prednisone; Mycophenolic Acid
• Other Study ID Numbers: P071226