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Completed

NCT Number: NCT00759811

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

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

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Key information

Conditions

Heart Failure Cardiovascular Diseases Heart Diseases Inflammation Myocardial Ischemia Pathologic Processes Pathological Conditions, Signs and Symptoms Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia

Porto Alegre, Rio Grande do Sul, 90620001, Brazil

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

methotrexate

Drug

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.

All patients will have evaluated at the baseline and after 12 weeks: physical capacity by the 6-minutes walk test, quality of life by the Brazilian edition SF-36 and inflammatory marker by C-reactive protein. They also will be tested for ALT, AST, blood cell count, creatinine, and prothrombin time at baseline, after 6 weeks and after 12 weeks.

Other names: Rheumatrex, Trexall

Placebo

Drug

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

All patients will have evaluated at the baseline and after 12 weeks: physical capacity by the 6-minutes walk test, quality of life by the Brazilian edition SF-36 and inflammatory marker by C-reactive protein. They also will be tested for ALT, AST, blood cell count, creatinine, and prothrombin time at baseline, after 6 weeks and after 12 weeks.

Other names: Control

Primary outcomes

  1. Change in Physical Capacity Measured Using the 6-minute Walk Test Distance

    Time frame: 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).

Secondary outcomes

  1. Improve in Heart Failure Functional Class Measured Using New York Heart Association

    Time frame: 12 weeks

  2. Improve in Quality of Life Measured Using the Brazilian Edition SF-36

    Time frame: 12 weeks

  3. Reduction of Inflammatory Marker Measured Using C-reactive Protein Blood Levels

    Time frame: 12 weeks

  4. Incidence of All Cause Mortality, Hospitalization for Worsening Heart Failure, Myocardial Infarct, Stroke or Myocardial Revascularization Need

    Time frame: 12 weeks

  5. Incidence of Adverse Effects of the Treatment

    Time frame: 12 weeks

Sponsors and collaborators

Lead sponsor

Instituto de Cardiologia do Rio Grande do Sul

Other

Registry information

Official study title

METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure: Randomized Double-blind, Placebo-controlled Trial (METIS Trial)

Acronym: METIS

Important dates

Study start
2007
Primary completion
2008
Study completion
2008
First posted
Sep 25, 2008
Registry last updated
May 8, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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