Study Comparing Two Tapering Strategies of Prednisone in Myasthenia Gravis

NCT ID: NCT00987116

Last Updated: 2017-10-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2017-09-30

Brief Summary

Pathology - Generalized myasthenia gravis (MG) is cause of muscle weakness that can have a significant impact on daily life activity but can also be, when respiratory or bulbar muscles are involved, life-threatening.

Rationale - Additionally to thymectomy, which indication of is still debated in absence of thymoma, the long-term treatment of generalized myasthenia gravis includes usually prednisone and azathioprine. However, the most used scheme for prescribing and tapering corticosteroid in MG resulted in a very important cumulative dose of prednisone. Indeed, at twelve month, more than 50 percent of patients are still daily treated with at least 18 mg of prednisone and the proportion of patients who are in remission and no longer taking prednisone is very low (Palace and NEWSOM Davis, Neurology 1998). Prolonged corticosteroid therapy is accompanied with various and major side effects, hypertension, osteoporosis, weight gain, glaucoma. Therefore, tapering, eventually discontinuing, prednisone earlier is a relevant therapeutic goal.

For this reason, the investigators will compare to the standard one, a strategy consisting of a rapid decrease in corticosteroid.

Objective - To assess whether, in patients with generalized MG requiring a long-term treatment with corticosteroids and azathioprine, that the strategy of rapid tapering allows discontinuing more rapidly the prednisone for equivalent efficacy than the classical strategy.

Detailed Description

Rapid strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for improvement or minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 0.75 mg/kg/day.

Classical strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 1.5 mg/kg/2days.

Duration of follow-up is 15 months.

In both arms, Myasthenia Muscular Score (MMS), activities of Daily Living Scale (ADLS), MGFA Clinical Classification and MGFA Post-Intervention Status as well as prednisone and azathioprine side effects will be monthly assessed by a senior neurologist who will be blind for treatment group. A second physician, who is aware of the patient's therapeutic group, will then prescribe prednisone dose and tapering for a month, according to MGFA Post-Intervention Status.

In case of worsening, prednisone dose will be increased. In case of exacerbation, the patients will be hospitalised for eventually IvIg infusion or plasma exchange. In case of a severe side effect, prednisone will be reduced irrespectively of MGFA Post-Intervention Status. In case of side effect, azathioprine will be replaced by mycophenolate mofetil.

Conditions

Myasthenia Gravis

Keywords

Myasthenia gravis; Steroids side effects; Comparison of strategies for tapering steroids; Generalized MG corresponding to grade III, IV or V of MGFA

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Starting dose Prednisone Azathioprine

Classical Strategy

Group Type: ACTIVE_COMPARATOR

Prednisone - Azathioprine

Intervention Type: DRUG

Rapid strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for improvement or minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 0.75 mg/kg/day.

Classical strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 1.5 mg/kg/2days.

Starting dose Prednisone - Azathioprine

Rapid strategy

Group Type: ACTIVE_COMPARATOR

Prednisone - Azathioprine

Intervention Type: DRUG

Rapid strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for improvement or minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 0.75 mg/kg/day.

Classical strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 1.5 mg/kg/2days.

Interventions

Prednisone - Azathioprine

Rapid strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for improvement or minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 0.75 mg/kg/day.

Classical strategy consists of decreasing the prednisone dose if at each monthly consultation the patient fulfils the criteria for minimal manifestation state, in order to discontinue it before twelve months. The starting dose is 1.5 mg/kg/2days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Written consent of the patient, after informing
• Generalized MG of grade III, IV or V - Classification MGFA
• Follow-up on 15 months possible and accepted by patients

Exclusion Criteria

• Age<18 or >80 years
• Pregnancy
• Myasthenia of grade I or II of MGFA
• Patients already treated with prednisone or azathioprine
• Contraindication for prednisone or azathioprine
• Other associated disease requiring a treatment with prednisone or azathioprine
• Weight >100kg
• Invasive thymoma

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tarek Sharshar, MD PH

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hopital Raymond Poincaré

Garches, , France

Countries

France

References

Sharshar T, Porcher R, Demeret S, Tranchant C, Gueguen A, Eymard B, Nadaj-Pakleza A, Spinazzi M, Grimaldi L, Birnbaum S, Friedman D, Clair B; MYACOR Study Group. Comparison of Corticosteroid Tapering Regimens in Myasthenia Gravis: A Randomized Clinical Trial. JAMA Neurol. 2021 Apr 1;78(4):426-433. doi: 10.1001/jamaneurol.2020.5407.

Reference Type: DERIVED

PMID: 33555314 (View on PubMed)

Other Identifiers

P051055

Identifier Type: -

Identifier Source: org_study_id