Clinical trial NCT01741558: The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS (TETHYS Trial)
Official title: The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS: Randomized Double-blind, Placebo-controlled Trial (TETHYS Trial)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Myocardial Infarction
Keywords: Myocardial Ischemia
Myocardial Infarction
Methotrexate
Inflammation
Anti-Inflammatory Agents
Inflammation Mediators
Lead sponsor: Instituto de Cardiologia do Rio Grande do Sul
Sponsor class: OTHER
Collaborators: name: Instituto de Cardiologia de Santa Catarina
First posted: 2012-12-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Area under the curve of creatine kinase
timeFrame: During 72 hours after the infarct
Secondary outcomes:
measure: Area under the curve for creatine kinase MB fraction and troponin I high sensitive
timeFrame: During 72 hours after the infarct
measure: Compare the peaks of CK, CK-MB and troponin I ultra-sensitive
timeFrame: During 72 hours after the infarct
measure: Compare the levels of high-sensitivity C-reactive protein at admission, after 72 hours and after 3 months
timeFrame: After 72 hours and after 3 months
measure: Compare the levels of erythrocyte sedimentation rate on admission and after 72 hours
timeFrame: On admission and after 72 hours
measure: Compare B-type natriuretic peptide (BNP) levels on admission, after 72 hours and after 3 months
timeFrame: On admission, after 72 hours and after 3 months
measure: Compare the "TIMI frame count" of the culprit artery
timeFrame: On admission
measure: Compare the Killip score on admission and after 72 hours
timeFrame: On admission and after 72 hours
measure: Assess ventricular ejection fraction with transthoracic echocardiography during the first 72 hours after 3 months
timeFrame: During the first 72 hours after 3 months
measure: Assess mortality at 3 months
timeFrame: At 3 months;
measure: Evaluate reinfarction in 3 months
timeFrame: In 3 months
measure: Rate side effects
timeFrame: In 72 hours
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia
state: Rio Grande do Sul
city: São José
country: Brazil
facility: Instituto de Cardiologia de Santa Catarina
state: Santa Catarina
Study officials:
affiliation: Instituto de Cardiologia do Rio Grande do Sul
name: Daniel M. Moreira, MD. MSc.
role: STUDY_CHAIR
affiliation: Instituto de Cardiologia do Rio Grande do Sul
name: Daniel M. Moreira, MD. MSc
role: STUDY_DIRECTOR
affiliation: Instituto de Cardiologia do Rio Grande do Sul
name: Daniel M. Moreira, MD. MSc.
role: PRINCIPAL_INVESTIGATOR
affiliation: Instituto de Cardiologia do Rio Grande do Sul
name: Carlos AM Gottschall, MD MSc PhD
role: STUDY_DIRECTOR
affiliation: Instituto de Cardiologia de Santa Catarina
name: Maria E. Lueneberg, MD.
role: STUDY_DIRECTOR
affiliation: Instituto de Cardiologia de Santa Catarina
name: Roberto L. da Silva, MD.
role: STUDY_DIRECTOR
affiliation: Instituto de Cardiologia de Santa Catarina
name: Tammuz Fattah, MD.
role: STUDY_DIRECTOR
References:
citation: Moreira DM, Lueneberg ME, da Silva RL, Fattah T, Gottschall CAM. MethotrexaTE THerapy in ST-Segment Elevation MYocardial InfarctionS: A Randomized Double-Blind, Placebo-Controlled Trial (TETHYS Trial). J Cardiovasc Pharmacol Ther. 2017 Nov;22(6):538-545. doi: 10.1177/1074248417699884. Epub 2017 Mar 22.