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

Myocardial Infarction Clinical Trial

— TETHYS  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01741558
• Other study ID #: UP 4747/12
• Secondary ID: CAAE 04482712.3.
• Status: Not yet recruiting
• Phase: Phase 2
• First received: December 3, 2012
• Last updated: April 5, 2013
• Start date: April 2013
• Est. completion date: December 2014

Study information

• Verified date: April 2013
• Source: Instituto de Cardiologia do Rio Grande do Sul
• Contact: Daniel M. Moreira, MSc.
• Phone: 554884175590
• Email: danielmedeirosmoreira[@]gmail.com
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: December 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

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
• 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.

Locations

Country	Name	City	State
Brazil	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

Sponsors (2)

Lead Sponsor	Collaborator
Instituto de Cardiologia do Rio Grande do Sul	Instituto de Cardiologia de Santa Catarina

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Compare the "TIMI frame count" of the culprit artery	Compare the "TIMI frame count" of the culprit artery	On admission	No
Secondary	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	No
Secondary	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	No
Secondary	Assess mortality at 3 months	Assess mortality at 3 months;	At 3 months;	No
Secondary	Evaluate reinfarction in 3 months	Evaluate reinfarction in 3 months	In 3 months	No
Secondary	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	Yes