The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS (TETHYS Trial)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS: Randomized Double-blind, Placebo-controlled Trial (TETHYS Trial)

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Methotrexate
* Drug: Riboflavin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 18 years; Chest pain suggestive of acute myocardial infarction initiated within 12 hours; Electrocardiogram with ST-segment elevation greater than or equal to 0.2 mV in at least 2 contiguous leads; Choice of primary angioplasty Exclusion Criteria: Prior acute myocardial infarction; Prior heart failure; Angioplasty in the last 3 months; Cardiac arrest or cardiogenic shock; History of renal insufficiency (serum creatinine greater than 2.0 mg/dl); History of alcohol abuse (consumption equal to or greater than 20 drinks per week); Illicit drug use; Evidence of rheumatoid arthritis; Neoplasia; Infectious diseases; Prior anemia (hematocrit below 30%); Use of anti-inflammatory hormonal or non-hormonal last week; Xanthines excessive consumption (more than two and a half cups of coffee or two and a half mate gourds); Pregnancy; Disagreement with the term of consent;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methotrexate<br>Established treatment associated with methotrexate | Drug: Methotrexate<br>* 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<br>* Other names: MTX;|
| Placebo Comparator: Placebo (Riboflavin)<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve of creatine kinase | 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 | During 72 hours after the infarct | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve for creatine kinase MB fraction and troponin I high sensitive | 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 | During 72 hours after the infarct | 
| Compare the peaks of CK, CK-MB and troponin I ultra-sensitive | Compare the peaks of CK, CK-MB and troponin I ultra-sensitive | During 72 hours after the infarct | 
| Compare the levels of high-sensitivity C-reactive protein at admission, after 72 hours and after 3 months | Compare the levels of high-sensitivity C-reactive at admission, after 72 hours and after 3 months | After 72 hours and after 3 months | 
| Compare the levels of erythrocyte sedimentation rate on admission and after 72 hours | Compare the levels of erythrocyte sedimentation rate on admission and after 72 hours | On admission and after 72 hours | 
| Compare B-type natriuretic peptide (BNP) levels 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 | On admission, after 72 hours and after 3 months | 
| Compare the TIMI frame count of the culprit artery | Compare the TIMI frame count of the culprit artery | On admission | 
| Compare the Killip score on admission and after 72 hours | Compare the Killip score on admission and after 72 hours; | On admission and after 72 hours | 
| Assess ventricular ejection fraction with transthoracic echocardiography during the first 72 hours after 3 months | Assess ventricular ejection fraction with transthoracic echocardiography during the first 72 hours after 3 months | During the first 72 hours after 3 months | 
| Assess mortality at 3 months | Assess mortality at 3 months; | At 3 months; | 
| Evaluate reinfarction in 3 months | Evaluate reinfarction in 3 months | In 3 months | 
| Rate side effects | 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). | In 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myocardial Ischemia, Myocardial Infarction, Methotrexate, Inflammation, Anti-Inflammatory Agents, Inflammation Mediators