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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 118
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Starting dose Prednisone Azathioprine
Classical Strategy
干预措施: Prednisone - Azathioprine (Drug)
Starting dose Prednisone - Azathioprine
Rapid strategy
干预措施: Prednisone - Azathioprine (Drug)
结局指标
主要结局
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.
时间窗: 15 months
次要结局
- 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)
- Cumulative dose of prednisone at twelve months(15 MONTHS)
- Frequency and type of complications related to prednisone.(15 MONTHS)
- Frequency and type of complications of azathioprine(15 MONTHS)
- Proportion of patients having reached minimal manifestation state 12 months(15 MONTHS)