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

Phase 2

• Conditions: Myocardial Infarction
• Interventions: Drug: Methotrexate; Drug: Riboflavin

• Registration Number: NCT01741558
• Lead Sponsor: Instituto de Cardiologia do Rio Grande do Sul

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.

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 Timeline

• Study First Submitted: 2012-12-03
• Study First Submitted QC: 2012-12-03
• Study First Posted: 2012-12-05
• Status Verified: 2013-04
• Study Start: 2013-04
• Last Update Submitted: 2013-04-05
• Last Update Posted: 2013-04-09
• Primary Completion: 2014-08
• Study Completion: 2014-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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

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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;

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Methotrexate	Methotrexate	Established treatment associated with methotrexate
Placebo (Riboflavin)	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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).

Trial Locations

Locations (2)

Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia; 🇧🇷 Porto Alegre, Rio Grande do Sul, Brazil

Instituto de Cardiologia de Santa Catarina; 🇧🇷 São José, Santa Catarina, Brazil