Study Comparing Two Tapering Strategies of Prednisone in Myasthenia Gravis (MYACOR)

• ClinicalTrials.gov Identifier: NCT00987116
• Recruitment Status: Completed
• First Posted: September 30, 2009
• Last Update Posted: October 13, 2017
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Myasthenia Gravis	Drug: Prednisone - Azathioprine	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 118 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparison of Two Tapering Strategies of Prednisone in Patients With Generalised Myasthenia Gravis Treated With Prednisone and Azathioprine: a Single-blind Randomised Controlled Multicenter Study
• Actual Study Start Date: June 2009
• Actual Primary Completion Date: July 2017
• Actual Study Completion Date: September 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Starting dose Prednisone Azathioprine; Classical Strategy	Drug: 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.
Active Comparator: Starting dose Prednisone - Azathioprine; Rapid strategy	Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients who have reach minimal manifestation state (according to MGFA criteria) and are not treated with prednisone after 12 months of treatment and have not relapsed during the next 3 months. [ Time Frame: 15 months ]

Secondary Outcome Measures :

1. Cumulative dose of prednisone at twelve months [ Time Frame: 15 MONTHS ]
2. Proportion of patients having reached minimal manifestation state 12 months [ Time Frame: 15 MONTHS ]
3. Time for reaching the improvement or minimal manifestation state (MGFA criteria) [ Time Frame: 15 MONTHS ]
4. Frequency of exacerbations within the first 15 months after randomization [ Time Frame: 15 MONTHS ]
5. Frequency of treatment by IvIg or plasma exchange within the first 15 months after randomization [ Time Frame: 15 MONTHS ]
6. Frequency and type of complications related to prednisone. [ Time Frame: 15 MONTHS ]
7. Frequency and type of complications of azathioprine [ Time Frame: 15 MONTHS ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

France

Hopital Raymond Poincaré

Garches, France, 92380

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

• Principal Investigator: Tarek Sharshar, MD PH; Assistance Publique - Hôpitaux de Paris

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT00987116
• Other Study ID Numbers: P051055
• First Posted: September 30, 2009
• Last Update Posted: October 13, 2017
• Last Verified: October 2017

Keywords provided by Assistance Publique - Hôpitaux de Paris:

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

Additional relevant MeSH terms:

Myasthenia Gravis; Muscle Weakness; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Prednisone; Azathioprine; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action