Clinical trial NCT00759811: METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure (METIS Trial)
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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Heart Failure
Myocardial Ischemia
Keywords: Heart Failure
Myocardial Ischemia
Methotrexate
Inflammation
Anti-Inflammatory Agents
Inflammation Mediators
Lead sponsor: Instituto de Cardiologia do Rio Grande do Sul
Sponsor class: OTHER
First posted: 2008-09-25
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Physical Capacity Measured Using the 6-minute Walk Test Distance
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Improve in Heart Failure Functional Class Measured Using New York Heart Association
timeFrame: 12 weeks
measure: Improve in Quality of Life Measured Using the Brazilian Edition SF-36
timeFrame: 12 weeks
measure: Reduction of Inflammatory Marker Measured Using C-reactive Protein Blood Levels
timeFrame: 12 weeks
measure: Incidence of All Cause Mortality, Hospitalization for Worsening Heart Failure, Myocardial Infarct, Stroke or Myocardial Revascularization Need
timeFrame: 12 weeks
measure: Incidence of Adverse Effects of the Treatment
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia
state: Rio Grande do Sul
Study officials:
affiliation: Instituto de Cardiologia do Rio Grande do Sul
name: Carlos AM Gottschall, MD MSc PhD
role: STUDY_DIRECTOR
affiliation: Instituto de Cardiologia do Rio Grande do Sul
name: Daniel M Moreira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto de Cardiologia do Rio Grande do Sul
name: Jefferson L Vieira, MD
role: STUDY_DIRECTOR
References:
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.