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

Primary Purpose

Heart Failure, Myocardial Ischemia

Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Methotrexate
Placebo
Sponsored by
Instituto de Cardiologia do Rio Grande do Sul
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Heart Failure, Myocardial Ischemia, Methotrexate, Inflammation, Anti-Inflammatory Agents, Inflammation Mediators

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Methotrexate

Placebo

Arm 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.

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Improve in Heart Failure Functional Class Measured Using New York Heart Association
Improve in Quality of Life Measured Using the Brazilian Edition SF-36
Reduction of Inflammatory Marker Measured Using C-reactive Protein Blood Levels
Incidence of All Cause Mortality, Hospitalization for Worsening Heart Failure, Myocardial Infarct, Stroke or Myocardial Revascularization Need
Incidence of Adverse Effects of the Treatment

Full Information

First Posted
September 24, 2008
Last Updated
March 29, 2013
Sponsor
Instituto de Cardiologia do Rio Grande do Sul
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1. Study Identification

Unique Protocol Identification Number
NCT00759811
Brief Title
METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure (METIS Trial)
Acronym
METIS
Official Title
METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure: Randomized Double-blind, Placebo-controlled Trial (METIS Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
December 2007 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
November 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto de Cardiologia do Rio Grande do Sul

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Myocardial Ischemia
Keywords
Heart Failure, Myocardial Ischemia, Methotrexate, Inflammation, Anti-Inflammatory Agents, Inflammation Mediators

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Methotrexate
Arm Type
Experimental
Arm 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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients receiving conventional treatment to heart failure who will receive placebo oral plus folic acid 5mg oral once a week for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
Rheumatrex, Trexall
Intervention 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. 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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Control
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Physical Capacity Measured Using the 6-minute Walk Test Distance
Description
The primary outcome of the study was the difference in 6MWT distance before and after the treatment (change in meters evaluated by t test).
Time Frame
Baseline and 12 weeks
Secondary Outcome Measure Information:
Title
Improve in Heart Failure Functional Class Measured Using New York Heart Association
Time Frame
12 weeks
Title
Improve in Quality of Life Measured Using the Brazilian Edition SF-36
Time Frame
12 weeks
Title
Reduction of Inflammatory Marker Measured Using C-reactive Protein Blood Levels
Time Frame
12 weeks
Title
Incidence of All Cause Mortality, Hospitalization for Worsening Heart Failure, Myocardial Infarct, Stroke or Myocardial Revascularization Need
Time Frame
12 weeks
Title
Incidence of Adverse Effects of the Treatment
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carlos AM Gottschall, MD MSc PhD
Organizational Affiliation
Instituto de Cardiologia do Rio Grande do Sul
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Daniel M Moreira, MD
Organizational Affiliation
Instituto de Cardiologia do Rio Grande do Sul
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jefferson L Vieira, MD
Organizational Affiliation
Instituto de Cardiologia do Rio Grande do Sul
Official's Role
Study Director
Facility Information:
Facility Name
Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia
City
Porto Alegre
State/Province
Rio Grande do Sul
ZIP/Postal Code
90620001
Country
Brazil

12. IPD Sharing Statement

Citations:
PubMed Identifier
19944358
Citation
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: 10.1016/j.cardfail.2009.06.439. Epub 2009 Aug 5.
Results Reference
result

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

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