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

Heart Failure Clinical Trial

— METIS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00759811
• Other study ID #: UP4062
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 24, 2008
• Last updated: March 29, 2013
• Start date: December 2007
• Est. completion date: November 2008

Study information

• Verified date: March 2013
• Source: Instituto de Cardiologia do Rio Grande do Sul
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Heart Failure
• Myocardial Ischemia

Intervention

Drug:
• 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. 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.
• Placebo
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.

Locations

Country	Name	City	State
Brazil	Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia	Porto Alegre	Rio Grande do Sul

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Cardiologia do Rio Grande do Sul

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

Moreira DM, Vieira JL, Gottschall CA. The effects of METhotrexate therapy on the physical capacity of patients with ISchemic heart failure: a randomized double-blind, placebo-controlled trial (METIS trial). J Card Fail. 2009 Dec;15(10):828-34. doi: 10.101 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Physical Capacity Measured Using the 6-minute Walk Test Distance	The primary outcome of the study was the difference in 6MWT distance before and after the treatment (change in meters evaluated by t test).	Baseline and 12 weeks	Yes
Secondary	Improve in Heart Failure Functional Class Measured Using New York Heart Association		12 weeks	Yes
Secondary	Improve in Quality of Life Measured Using the Brazilian Edition SF-36		12 weeks	Yes
Secondary	Reduction of Inflammatory Marker Measured Using C-reactive Protein Blood Levels		12 weeks	Yes
Secondary	Incidence of All Cause Mortality, Hospitalization for Worsening Heart Failure, Myocardial Infarct, Stroke or Myocardial Revascularization Need		12 weeks	No
Secondary	Incidence of Adverse Effects of the Treatment		12 weeks	No