The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS (TETHYS Trial)
Study Details
Study Description
Brief Summary
Experimental studies suggest that anti-inflammatory and immunomodulatory drugs could reduce the inflammatory profile in acute ischemic disease and reduce the area of ischemia. Methotrexate is a drug that has shown promise in ischemic disease in animal studies.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Atherosclerosis and ischemic disease have clear association with inflammation. There is an anti-inflammatory action of methotrexate by increasing adenosine. Experimental studies demonstrate reduction of infarct induced in animals treated with methotrexate. We expect a reduction in the area under the curve of creatine kinase (CK), creatine kinase MB fraction (CK-MB) and Troponin I high sensitive, decreased levels of B-type natriuretic peptide (BNP) and improvement in left ventricular ejection fraction.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Methotrexate Established treatment associated with methotrexate |
Drug: Methotrexate
The treatment group will receive a bolus dose of 0.05 mg/kg of methotrexate before primary angioplasty followed by 0.05 mg/kg per hour for 6 hours
Other Names:
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| Placebo Comparator: Placebo (Riboflavin) Established treatment associated with placebo (riboflavin sodium fosfate 0.1%). We use riboflavin in placebo group to remain the double-blind fashion: methotrexate has a yellow color and riboflavin in that concentration has the same color. |
Drug: Riboflavin
We use riboflavin in placebo group to remain the double-blind fashion: methotrexate has a yellow color and riboflavin in that concentration has the same color.
|
Outcome Measures
Primary Outcome Measures
- Area under the curve of creatine kinase [During 72 hours after the infarct]
The primary end point was the reduction of the size of the infarct as assessed by the area under the curve (AUC) (expressed in arbitrary units) for creatine kinase (CK) during 72 hours after the infarct
Secondary Outcome Measures
- Area under the curve for creatine kinase MB fraction and troponin I high sensitive [During 72 hours after the infarct]
The primary end point was the reduction of the size of the infarct as assessed by the area under the curve (AUC) (expressed in arbitrary units) for creatine kinase MB fraction(CK-MB) and Troponin I high sensitive during 72 hours after the infarct
- Compare the peaks of CK, CK-MB and troponin I ultra-sensitive [During 72 hours after the infarct]
Compare the peaks of CK, CK-MB and troponin I ultra-sensitive
- Compare the levels of high-sensitivity C-reactive protein at admission, after 72 hours and after 3 months [After 72 hours and after 3 months]
Compare the levels of high-sensitivity C-reactive at admission, after 72 hours and after 3 months
- Compare the levels of erythrocyte sedimentation rate on admission and after 72 hours [On admission and after 72 hours]
Compare the levels of erythrocyte sedimentation rate on admission and after 72 hours
- Compare B-type natriuretic peptide (BNP) levels on admission, after 72 hours and after 3 months [On admission, after 72 hours and after 3 months]
Compare B-type natriuretic peptide (BNP) levels on admission, after 72 hours and after 3 months
- Compare the "TIMI frame count" of the culprit artery [On admission]
Compare the "TIMI frame count" of the culprit artery
- Compare the Killip score on admission and after 72 hours [On admission and after 72 hours]
Compare the Killip score on admission and after 72 hours;
- Assess ventricular ejection fraction with transthoracic echocardiography during the first 72 hours after 3 months [During the first 72 hours after 3 months]
Assess ventricular ejection fraction with transthoracic echocardiography during the first 72 hours after 3 months
- Assess mortality at 3 months [At 3 months;]
Assess mortality at 3 months;
- Evaluate reinfarction in 3 months [In 3 months]
Evaluate reinfarction in 3 months
- Rate side effects [In 72 hours]
Evaluation in 72 hours the changes in the levels of hematocrit, hemoglobin, leukocytes and platelets, changes in the levels of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase and prothrombin Time; changes in the levels of plasma creatinine, gastrointestinal effects (oral ulcers, diarrhea, nausea and vomiting), skin changes (rash, pruritus, and alopecia) and pulmonary effects (pneumonitis and pneumonia).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age over 18 years;
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Chest pain suggestive of acute myocardial infarction initiated within 12 hours;
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Electrocardiogram with ST-segment elevation greater than or equal to 0.2 mV in at least 2 contiguous leads;
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Choice of primary angioplasty
Exclusion Criteria:
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Prior acute myocardial infarction;
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Prior heart failure;
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Angioplasty in the last 3 months;
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Cardiac arrest or cardiogenic shock;
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History of renal insufficiency (serum creatinine greater than 2.0 mg/dl);
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History of alcohol abuse (consumption equal to or greater than 20 drinks per week);
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Illicit drug use;
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Evidence of rheumatoid arthritis;
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Neoplasia;
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Infectious diseases;
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Prior anemia (hematocrit below 30%);
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Use of anti-inflammatory hormonal or non-hormonal last week;
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Xanthines excessive consumption (more than two and a half cups of coffee or two and a half mate gourds);
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Pregnancy;
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Disagreement with the term of consent;
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia | Porto Alegre | Rio Grande do Sul | Brazil | 90620001 |
| 2 | Instituto de Cardiologia de Santa Catarina | São José | Santa Catarina | Brazil | 88103901 |
Sponsors and Collaborators
- Instituto de Cardiologia do Rio Grande do Sul
- Instituto de Cardiologia de Santa Catarina
Investigators
- Study Chair: Daniel M. Moreira, MD. MSc., Instituto de Cardiologia do Rio Grande do Sul
- Study Director: Daniel M. Moreira, MD. MSc, Instituto de Cardiologia do Rio Grande do Sul
- Principal Investigator: Daniel M. Moreira, MD. MSc., Instituto de Cardiologia do Rio Grande do Sul
- Study Director: Carlos AM Gottschall, MD MSc PhD, Instituto de Cardiologia do Rio Grande do Sul
- Study Director: Maria E. Lueneberg, MD., Instituto de Cardiologia de Santa Catarina
- Study Director: Roberto L. da Silva, MD., Instituto de Cardiologia de Santa Catarina
- Study Director: Tammuz Fattah, MD., Instituto de Cardiologia de Santa Catarina
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UP 4747/12
- CAAE 04482712.3.0000.5333