METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure: Randomized Double-blind, Placebo-controlled Trial (METIS Trial)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Change in Physical Capacity Measured Using the 6-minute Walk Test Distance
研究概览
简要总结
The aim of the study is to evaluate the efficacy of methotrexate to improve physical capacity in patients with symptomatic ischemic heart failure.
详细描述
Recent studies have showed the importance of proinflammatory mediators in the heart failure. However, there is a lack of benefit of therapies that tried to neutralize these mediators.
Methotrexate has adenosine-mediated anti-inflammatory effects in rheumatoid arthritis and psoriasis. Methotrexate limits infarct size via this adenosine-dependent mechanisms in heart of dogs (J Cardiovasc Pharmacol. 2004 Apr;43(4):574-9). A recent trial showed that this drug reduced proinflammatory mediators in patients with heart failure (Am Heart J. 2006 Jan;151(1):62-8).
These data suggest that methotrexate may improve physical capacity in patients ischemic heart failure reducing inflammation, but a randomized clinical trial is necessary to prove it.
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
- Quadruple (Participant, Care Provider, Investigator, 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
- •Heart failure functional class measured using the New York Heart Association classification class II, III or IV
- •Left ventricular fraction <0.45 at the ventriculography
- •Angiographic coronary lesions higher than 50% or coronary lesion revascularized (coronary artery bypass or percutaneous transluminal coronary angioplasty)
排除标准
- •Myocardial infarction in the past four months
- •Coronary artery bypass or percutaneous transluminal coronary angioplasty in the past four months
- •Left ventricular disfunction diagnosed during a acute coronary syndrome
- •Those who require revascularization in the following 12 weeks
- •Hepatic disease (ALT and AST higher than the upper limit of the reference value)
- •Renal failure (plasma creatinine higher than 2.0mg/dl)
- •Alcoholism (20 doses per week or more)
- •Illegal drug use
- •Rheumatoid arthritis or other inflammatory diseases
- •Infectious disease
- •Anemia (hematocrit lower than 30%)
- •Currently on any anti-inflammatory drugs
- •Difficulty in walking
- •Unable to understand/complete the 36-item Short Form health survey (SF-36)
- •Those who do not give informed consent
研究组 & 干预措施
Methotrexate
Patients receiving conventional treatment to heart failure who will receive methotrexate 7.5mg oral plus folic acid 5mg oral once a week for 12 weeks.
干预措施: Methotrexate (Drug)
Placebo
Patients receiving conventional treatment to heart failure who will receive placebo oral plus folic acid 5mg oral once a week for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Physical Capacity Measured Using the 6-minute Walk Test Distance
时间窗: Baseline and 12 weeks
The primary outcome of the study was the difference in 6MWT distance before and after the treatment (change in meters evaluated by t test).
次要结局
- Improve in Heart Failure Functional Class Measured Using New York Heart Association(12 weeks)
- Improve in Quality of Life Measured Using the Brazilian Edition SF-36(12 weeks)
- Reduction of Inflammatory Marker Measured Using C-reactive Protein Blood Levels(12 weeks)
- Incidence of All Cause Mortality, Hospitalization for Worsening Heart Failure, Myocardial Infarct, Stroke or Myocardial Revascularization Need(12 weeks)
- Incidence of Adverse Effects of the Treatment(12 weeks)
研究者
Daniel Medeiros Moreira
MSc.
Instituto de Cardiologia do Rio Grande do Sul