Study Comparing Two Tapering Strategies of Prednisone in Myasthenia Gravis (MYACOR)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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 | Intervention | Phase |
|---|---|---|
|
Myasthenia Gravis |
Drug: Prednisone - Azathioprine |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) 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 |
- 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 ] [ Designated as safety issue: Yes ]
- Cumulative dose of prednisone at twelve months [ Time Frame: 15 MONTHS ] [ Designated as safety issue: Yes ]
- Proportion of patients having reached minimal manifestation state 12 months [ Time Frame: 15 MONTHS ] [ Designated as safety issue: Yes ]
- Time for reaching the improvement or minimal manifestation state (MGFA criteria) [ Time Frame: 15 MONTHS ] [ Designated as safety issue: Yes ]
- Frequency of exacerbations within the first 15 months after randomization [ Time Frame: 15 MONTHS ] [ Designated as safety issue: Yes ]
- Frequency of treatment by IvIg or plasma exchange within the first 15 months after randomization [ Time Frame: 15 MONTHS ] [ Designated as safety issue: Yes ]
- Frequency and type of complications related to prednisone. [ Time Frame: 15 MONTHS ] [ Designated as safety issue: Yes ]
- Frequency and type of complications of azathioprine [ Time Frame: 15 MONTHS ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 114 |
| Study Start Date: | June 2009 |
| Estimated Study Completion Date: | December 2013 |
| Estimated Primary Completion Date: | September 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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. Other Name: Prednisone - Azathioprine
|
|
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. Other Name: Prednisone - Azathioprine
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| Contact: Tarek SHARSHAR, MD,PHD | +33 (0)1 47 10 77 80 | tarek.sharshar@rpc.aphp.fr |
| France | |
| Hopital Raymond Poincaré | Recruiting |
| Garches, France, 92380 | |
| Contact: Tarek SHARSHAR, MD,PHD '0)1 47 10 77 80 ext +33 tarek.sharshar@rpc.aphp.fr | |
| Principal Investigator: | Tarek Sharshar, MD PH | Assistance Publique - Hôpitaux de Paris |
More Information
No publications provided
| Responsible Party: | Assistance Publique - Hôpitaux de Paris |
| ClinicalTrials.gov Identifier: | NCT00987116 History of Changes |
| Other Study ID Numbers: | P051055 |
| Study First Received: | September 29, 2009 |
| Last Updated: | December 12, 2011 |
| Health Authority: | France: Ministry of Health France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) |
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 Autoimmune Diseases of the Nervous System Nervous System Diseases Neuromuscular Junction Diseases Neuromuscular Diseases Autoimmune Diseases Immune System Diseases Muscular Diseases Musculoskeletal Diseases Neuromuscular Manifestations Neurologic Manifestations Pathologic Processes Signs and Symptoms Azathioprine |
Prednisone Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal |
ClinicalTrials.gov processed this record on May 21, 2013