Heart FailurePhase 2/3METISNCT00759811
METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure (METIS Trial)
A Phase 2/3 study testing Methotrexate in people with Heart Failure and Myocardial Ischemia, run by Instituto de Cardiologia do Rio Grande do Sul at 1 site in Brazil.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure, Myocardial Ischemia
- What is being tested?
- Methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteBrazil
- Study dates
- Dec 2007to Nov 2008
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia
Porto Alegre, Rio Grande do Sul, 90620001
About this study
Official title: METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure: Randomized Double-blind, Placebo-controlled Trial (METIS Trial)
The aim of the study is to evaluate the efficacy of methotrexate to improve physical capacity in patients with symptomatic ischemic heart failure.
Read the 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.
- Conditions
- Heart Failure, Myocardial Ischemia
- Being tested
- Methotrexate, Placebo
- Keywords
- Heart Failure, Myocardial Ischemia, Methotrexate, Inflammation, Anti-Inflammatory Agents, Inflammation Mediators
- Medical subject headings
- Heart Failure, Myocardial Ischemia, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
Also called Rheumatrex, Trexall
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.
PlaceboDrug
Also called Control
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Methotrexate |
| 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline and 12 weeks
Secondary outcomes (5)
Improve in Heart Failure Functional Class Measured Using New York Heart Association
Measured: 12 weeks
Improve in Quality of Life Measured Using the Brazilian Edition SF-36
Measured: 12 weeks
Reduction of Inflammatory Marker Measured Using C-reactive Protein Blood Levels
Measured: 12 weeks
Incidence of All Cause Mortality, Hospitalization for Worsening Heart Failure, Myocardial Infarct, Stroke or Myocardial Revascularization Need
Measured: 12 weeks
Incidence of Adverse Effects of the Treatment
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2008 (estimated)
- Study startDec 2007
- Primary completionNov 2008
- Study completionNov 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Instituto de Cardiologia do Rio Grande do Sul
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Medeiros Moreira, Instituto de Cardiologia do Rio Grande do Sul
- Investigators
- Carlos AM Gottschall, MD MSc PhD, Study director, Instituto de Cardiologia do Rio Grande do SulDaniel M Moreira, MD, Principal investigator, Instituto de Cardiologia do Rio Grande do SulJefferson L Vieira, MD, Study director, Instituto de Cardiologia do Rio Grande do Sul
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00759811
- Sponsor's protocol ID
- UP4062
- Acronym
- METIS
- Status last verified
- Mar 2013
- First submitted
- 24 Sep 2008
- Last updated
- 8 May 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 19944358
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- METhotrexate Therapy Effects in the Physical Capacity of Patients With ISchemic Heart Failure: Randomized Double-blind, Placebo-controlled Trial (METIS Trial)
- ClinicalTrials.gov ID
- NCT00759811
- Acronym / sponsor ID
- METIS / UP4062
- Conditions
- Heart Failure, Myocardial Ischemia
- Keywords
- Heart Failure, Myocardial Ischemia, Methotrexate, Inflammation, Anti-Inflammatory Agents, Inflammation Mediators
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Instituto de Cardiologia do Rio Grande do SulUniversity, hospital or other
- Study start
- Dec 2007
- Primary completion
- Nov 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 25 Sep 2008 (estimated)
- Results
- Posted 8 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methotrexate | Experimental | Drug: MethotrexatePatients 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 comparator | Drug: PlaceboPatients receiving conventional treatment to heart failure who will receive placebo oral plus folic acid 5mg oral once a week for 12 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethotrexateAlso: Rheumatrex, TrexallPatients 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. | Drug | Methotrexate |
| PlaceboAlso: ControlPatients 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. | Drug | Placebo |
Primary outcome
Change in Physical Capacity Measured Using the 6-minute Walk Test Distance
Time frame: 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).
5 secondary outcomes
Improve in Heart Failure Functional Class Measured Using New York Heart Association
Time frame: 12 weeks
Improve in Quality of Life Measured Using the Brazilian Edition SF-36
Time frame: 12 weeks
Reduction of Inflammatory Marker Measured Using C-reactive Protein Blood Levels
Time frame: 12 weeks
Incidence of All Cause Mortality, Hospitalization for Worsening Heart Failure, Myocardial Infarct, Stroke or Myocardial Revascularization Need
Time frame: 12 weeks
Incidence of Adverse Effects of the Treatment
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19944358Moreira 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carlos AM Gottschall, MD MSc PhD study director
Instituto de Cardiologia do Rio Grande do Sul
Daniel M Moreira, MD principal investigator
Instituto de Cardiologia do Rio Grande do Sul
Jefferson L Vieira, MD study director
Instituto de Cardiologia do Rio Grande do Sul
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Methotrexate in people with Heart Failure and Myocardial Ischemia, run by Instituto de Cardiologia do Rio Grande do Sul at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Physical Capacity Measured Using the 6-minute Walk Test Distance (time frame: Baseline and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00759811, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2013.