Clinical Trial: Study Comparing Two Tapering Strategies of Prednisone in Myasthenia Gravis

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Comparison of Two Tapering Strategies of Prednisone in Patients With Generalised Myasthenia Gravis Treated With Prednisone and Azathioprine: a Single-blind Randomised Cont

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 Summary:

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.


Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: 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 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

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


Original Secondary Outcome: Same as current

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: September 29, 2009
Date Started: June 2009
Date Completion: May 2017
Last Updated: May 2, 2017
Last Verified: November 2016