Study Comparing Two Tapering Strategies of Prednisone in Myasthenia Gravis

NCT00987116 | Completed Phase 4 DMC

• 1 other identifier: P051055
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (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.

  15 months

Secondary Outcomes (7)

• Cumulative dose of prednisone at twelve months

  15 MONTHS

• Proportion of patients having reached minimal manifestation state 12 months

  15 MONTHS

• Time for reaching the improvement or minimal manifestation state (MGFA criteria)

  15 MONTHS

• Frequency of exacerbations within the first 15 months after randomization

  15 MONTHS

• Frequency of treatment by IvIg or plasma exchange within the first 15 months after randomization

  15 MONTHS

Study Arms (2)

Starting dose Prednisone Azathioprine

ACTIVE COMPARATOR

Classical Strategy

Drug: Prednisone - Azathioprine

Starting dose Prednisone - Azathioprine

ACTIVE COMPARATOR

Rapid strategy

Drug: Prednisone - Azathioprine

Interventions

Prednisone - Azathioprine 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; Starting dose Prednisone Azathioprine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hopital Raymond Poincaré

Garches, 92380, France

Location

Related Publications (1)

• 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.

  PMID: 33555314 DERIVED

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Tarek Sharshar, MD PH

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2009
• First Posted: September 30, 2009
• Study Start: June 1, 2009
• Primary Completion: July 1, 2017
• Study Completion: September 1, 2017
• Last Updated: October 13, 2017

Record last verified: 2017-10

Locations

FR (1)