- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00987116
Study Comparing Two Tapering Strategies of Prednisone in Myasthenia Gravis (MYACOR)
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
-
Garches, France, 92380
- Hôpital Raymond Poincaré
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Starting dose Prednisone Azathioprine
Classical Strategy
|
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
|
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
15 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Cumulative dose of prednisone at twelve months
Time Frame: 15 MONTHS
|
15 MONTHS
|
Proportion of patients having reached minimal manifestation state 12 months
Time Frame: 15 MONTHS
|
15 MONTHS
|
Time for reaching the improvement or minimal manifestation state (MGFA criteria)
Time Frame: 15 MONTHS
|
15 MONTHS
|
Frequency of exacerbations within the first 15 months after randomization
Time Frame: 15 MONTHS
|
15 MONTHS
|
Frequency of treatment by IvIg or plasma exchange within the first 15 months after randomization
Time Frame: 15 MONTHS
|
15 MONTHS
|
Frequency and type of complications related to prednisone.
Time Frame: 15 MONTHS
|
15 MONTHS
|
Frequency and type of complications of azathioprine
Time Frame: 15 MONTHS
|
15 MONTHS
|
Collaborators and Investigators
Investigators
- Principal Investigator: Tarek Sharshar, MD PH, Assistance Publique - Hôpitaux de Paris
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Neoplasms
- Autoimmune Diseases of the Nervous System
- Autoimmune Diseases
- Neoplasms by Site
- Neurologic Manifestations
- Musculoskeletal Diseases
- Muscular Diseases
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Neuromuscular Manifestations
- Nervous System Neoplasms
- Paraneoplastic Syndromes, Nervous System
- Paraneoplastic Syndromes
- Neuromuscular Junction Diseases
- Muscle Weakness
- Myasthenia Gravis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Prednisone
- Azathioprine
Other Study ID Numbers
- P051055
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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