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

Sponsored by:	Instituto de Cardiologia do Rio Grande do Sul
Information provided by:	Instituto de Cardiologia do Rio Grande do Sul
ClinicalTrials.gov Identifier:	NCT00759811

Purpose

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

Condition	Intervention	Phase
Heart Failure Myocardial Ischemia	Drug: Methotrexate Drug: Placebo	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Single Group Assignment, Efficacy Study
Official Title:	METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure: Randomized Double-blind, Placebo-controlled Trial (METIS Trial)

Resource links provided by NLM:

MedlinePlus related topics: Heart Failure

Drug Information available for: Methotrexate

U.S. FDA Resources

Further study details as provided by Instituto de Cardiologia do Rio Grande do Sul:

Primary Outcome Measures:

Improve in physical capacity measured using the 6-minute walk test distance [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Improve in quality of life measured using the Brazilian edition SF-36 [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Improve in heart failure functional class measured using New York Heart Association [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Reduction of inflammatory marker measured using C-reactive protein blood levels [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Incidence of all cause mortality, hospitalization for worsening heart failure, myocardial infarct, stroke or myocardial revascularization need [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Incidence of adverse effects of the treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment:	50
Study Start Date:	December 2007
Study Completion Date:	November 2008
Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Methotrexate: Experimental 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.	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: Placebo Comparator Patients receiving conventional treatment to heart failure who will receive placebo oral plus folic acid 5mg oral once a week for 12 weeks.	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. 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.

Arms

Assigned Interventions

Methotrexate: Experimental

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.

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: Placebo Comparator

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

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. 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.

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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00759811

Locations

Brazil, Rio Grande do Sul
Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia
Porto Alegre, Rio Grande do Sul, Brazil, 90620001

Sponsors and Collaborators

Instituto de Cardiologia do Rio Grande do Sul

Investigators

Study Director:	Carlos AM Gottschall, MD MSc PhD	Instituto de Cardiologia do Rio Grande do Sul
Principal Investigator:	Daniel M Moreira, MD	Instituto de Cardiologia do Rio Grande do Sul
Study Director:	Jefferson L Vieira, MD	Instituto de Cardiologia do Rio Grande do Sul

More Information

No publications provided

Responsible Party:	Instituto de Cardiologia do Rio Grande do Sul ( Daniel Medeiros Moreira )
Study ID Numbers:	UP4062
Study First Received:	September 24, 2008
Last Updated:	August 7, 2009
ClinicalTrials.gov Identifier:	NCT00759811 History of Changes
Health Authority:	Brazil: Ethics Committee

Keywords provided by Instituto de Cardiologia do Rio Grande do Sul:

Heart Failure
Myocardial Ischemia
Methotrexate

Inflammation
Anti-Inflammatory Agents
Inflammation Mediators

Study placed in the following topic categories:

Thrombin
Anti-Inflammatory Agents
Antimetabolites
Heart Failure
Heart Diseases
Immunologic Factors
Myocardial Ischemia
Vascular Diseases
Folate

Ischemia
Folinic Acid
Folic Acid Antagonists
Immunosuppressive Agents
Vitamin B9
Inflammation
Folic Acid
Methotrexate
Antirheumatic Agents

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Myocardial Ischemia
Physiological Effects of Drugs
Reproductive Control Agents
Pathologic Processes
Therapeutic Uses
Abortifacient Agents
Methotrexate
Cardiovascular Diseases

Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Heart Failure
Heart Diseases
Vascular Diseases
Enzyme Inhibitors
Ischemia
Abortifacient Agents, Nonsteroidal
Folic Acid Antagonists
Immunosuppressive Agents
Pharmacologic Actions
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 11, 2009