Study Comparing Two Tapering Strategies of Prednisone in Myasthenia Gravis - Full Text View

Sponsor:	Assistance Publique - Hôpitaux de Paris
Information provided by (Responsible Party):	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00987116

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

Resource links provided by NLM:

MedlinePlus related topics: Myasthenia Gravis

Drug Information available for: Prednisone Azathioprine Azathioprine Sodium

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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

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

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00987116

Contacts

Contact: Tarek SHARSHAR, MD,PHD

+33 (0)1 47 10 77 80

tarek.sharshar@rpc.aphp.fr

Locations

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

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

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 - French Health Products Safety Agency

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 23, 2012