A Canadian Multicenter, Randomized, Double-Blind Placebo-Controlled Study of Methotrexate and Folic Acid in Systemic Lupus Erythematosus: A Phase III Trial.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 2
- 主要终点
- SLAM - Systemic Lupus Activity Measure
研究概览
简要总结
The treatment of systemic lupus erythematosus (SLE) has been aimed at decreasing mortality and morbidity because the etiology of the disease is unknown. The general aim of this multicentre randomized placebo-controlled trial of low dose intermittent methotrexate with folic acid is to establish whether methotrexate shows efficacy and safety in controlling disease activity in SLE and preventing flares in disease activity or development of end-organ damage. A second aim will be to document the steroid sparing effect of methotrexate in SLE. A Third aim will be to measure toxicity and utility of methotrexate with folic acid and to perform effectiveness and utility analyses.
详细描述
SLE is a chronic systemic autoimmune and inflammatory disease. Approximately 65% of patients develop SLE between 16 and 55 years of age, and it is 8-10 times more common in women. Overall prevalence is estimated at 40-50 per 100,000 individuals in the US. SLE typically includes periods of remission and flares. Systemic manifestation of SLE includes fatigue, fever, arthralgia, weight loss, and skin rash. Disease progression is variable and unpredictable from one individual to the next. Treatment is aimed at preventing damage due to inflammation of the involved tissues. Death occur primarily from severe systemic infections and renal insufficiency. Futhermore, patients with long-standing SLE on chronic steroid use may succumb from atherosclerotic complications such as myocardial infarction.
The mainstay of treatment of acute disease manifestations is steroids, in particular,prednisone. Once started, it is difficult to reduce or stop treatment without new flares or severe steroid withdrawal. Longitudinal studies in SLE cannot dissociate morbidity caused by the disease from that caused by prolonged steroid use.
Specific Objectives:
- To measure the efficacy, safety and tolerance of methotrexate with folic acid compared to placebo with folic acid.
- To measure the steroid-sparing effects of methotrexate in SLE
- To perform a cost-effectiveness and a cost-utility analysis of methotrexate with folic acid using generic and disease specific health status measures.
Qualification for the study:
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
- Double
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •men and women with diagnosis of SLE
- •18 years and above
- •negative pregnancy test for female subjects of child-bearing age and must accept not to attempt to get pregnant during the period of the study
- •Subject with active disease as defined by SLAM of at least 8
- •SLICC/ACR damage index of less or equal to 15
- •Subject must be on stable does of NSAIDs, prednisone, or antimalarial (chloroquine sulfate or hydroxychloroquine) at least 4 weeks preceding the study
- •subjects can be under other medications as long as condition or treatment will not interfere with the experimental medications and assessments
- •must understand either French or English and can give written informed consent
排除标准
- •previous history of hypersensitivity or intolerance to methotrexate or folic acid
- •total SLAM of less than 8 or total SLICC/ACR score of more than
- •history of medical non-compliance or inability to comply with instructions
- •subject who have received intra-articular or intramuscular corticosteroids in the four weeks prior to study entry.
- •clinically significant acute or chronic liver disease with the exception of autoimmune liver disease
- •alcohol use in excess of 2 ounces of 100 proof liquor or its equivalent/week
- •insulin requiring diabetes mellitus with morbid obesity
- •renal impairment such that the serum creatinine is more than or equal to 175 umol/I (SI units) or 2.0 mg/dl
- •interstitial lung disease as defined by an abnormal chest x-ray or decrease diffusion capacity (DLCO < 70% of predicted) without evidence of pulmonary hypertension.
- •WBC count ,3,000/ cubic mm. and/or platelet count ,80,000/ cubic mm.
- •prior use of methotrexate to treat SLE
- •use of sulfa drugs that may potentiate the folate antagonistic effects of MTX
- •non-steroidal anti-inflammatory drugs will be allowed throughout the trial unless there is evidence of renal failure or other contra-indications to these drugs. Their con-comitant use with MTX is routine in patients with rheumatoid arthritis.
- •use of another cytotoxic or immunosuppressive drug such as cyclophosphamide, azathioprine, chlorambucil, cyclosporin or trimetoprime currently or in the preceding 6 months.
- •current participation in any other drug trial or participation in such a trial in the previous one month.
- •serologic evidence of infection with HIV
- •biologic potential for pregnancy and not utilizing effective means of contraception
- •recently (less than 6 months) diagnosed malignancy
- •vitamin B12 deficiency
结局指标
主要结局
SLAM - Systemic Lupus Activity Measure
时间窗: at one year
Daily dose of prednisone
时间窗: at one year
次要结局
- SLICC DI - Systemic Lupus International Collaborating Clinic Damage Index(at one year)
- SF-36 - Short Form 36(at one year)
- SLEDAI - Systemic Lupus Erythematosus Disease Activity Index(at one year)