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

Phase 2

Completed

• Conditions: Heart Failure; Myocardial Ischemia
• Interventions: Drug: Methotrexate; Drug: Placebo

• Registration Number: NCT00759811
• Lead Sponsor: Instituto de Cardiologia do Rio Grande do Sul

Brief Summary

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

Detailed 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2007-12
• Study First Submitted: 2008-09-24
• Study First Submitted QC: 2008-09-24
• Study First Posted: 2008-09-25
• Primary Completion: 2008-11
• Study Completion: 2008-11
• Results First Submitted: 2009-09-04
• Status Verified: 2013-03
• Results First Submitted QC: 2013-03-29
• Last Update Submitted: 2013-03-29
• Results First Posted: 2013-05-08
• Last Update Posted: 2013-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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)

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Change in Physical Capacity Measured Using the 6-minute Walk Test Distance	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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia; 🇧🇷 Porto Alegre, Rio Grande do Sul, Brazil