METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure (METIS Trial)

Instituto de Cardiologia do Rio Grande do Sul

Status and phase: Completed; Phase 3; Phase 2

Conditions: Myocardial Ischemia; Heart Failure

Treatments: Drug: Methotrexate; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT00759811

UP4062

Details and patient eligibility

About

The aim of the study is to evaluate the efficacy of methotrexate to improve physical capacity in patients with symptomatic ischemic heart failure.

Full description

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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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)

Exclusion criteria

• 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
• Neoplasm
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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50 participants in 2 patient groups, including a placebo group

Methotrexate

Experimental group

Description:

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.

Treatment:

Drug: Methotrexate

Placebo

Placebo Comparator group

Description:

Patients receiving conventional treatment to heart failure who will receive placebo oral plus folic acid 5mg oral once a week for 12 weeks.

Treatment:

Drug: Placebo