title: Rationale and design of the TETHYS trial: the effects of methotrexate therapy on myocardial infarction with ST-segment elevation.
abstract: BACKGROUND
  Methotrexate is a drug that has shown anti-ischemic effects in animal studies and positive results in heart failure clinical trials.
  
  
  METHODS
  We will randomly assign 80 patients with acute myocardial infarction to receive methotrexate (0.05 mg/kg bolus followed by 0.05 mg/kg/h for 6 h) or matching placebo. The primary outcome will be the area under the curve (AUC) for creatine kinase (CK) release for 72 h. Secondary outcomes will be the peak levels of CK, CK-MB fraction and troponin I, AUC for CK-MB and troponin I, levels of B-type natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) at admission and at 30 days, left ventricular ejection fraction (LVEF) at baseline and at 30 days, death, TIMI (thrombolysis in myocardial infarction) frame count in the culprit artery, Killip score after 72 h and rate of reinfarction at 30 days.
  
  
  RESULTS
  We expect a reduction in the AUC for CK, CK-MB and troponin release in the methotrexate group compared to the placebo group. We also expect a reduction in the levels of BNP, hsCRP and ESR and an improvement of LVEF and TIMI frame count in the methotrexate group.
  
  
  CONCLUSIONS
  This trial may be the first to demonstrate the anti-inflammatory and anti-ischemic effects of methotrexate in patients with acute myocardial infarction.
authors.affiliation: Instituto de Cardiologia de Santa Catarina, São José, and Instituto de Cardiologia do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Daniel Medeiros
authors.initials: DM
authors.lastname: Moreira
authors.forename: Maria Emilia
authors.initials: ME
authors.lastname: Lueneberg
authors.forename: Roberto Leo
authors.initials: RL
authors.lastname: da Silva
authors.forename: Tammuz
authors.initials: T
authors.lastname: Fattah
authors.forename: Carlos Antonio
authors.initials: CA
authors.lastname: Mascia Gottschall
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D003402:Creatine Kinase / Q000378:metabolism; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D004311:Double-Blind Method; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D013223:Statistics as Topic / Q000379:methods; D016896:Treatment Outcome; D014336:Troponin / Q000378:metabolism; D055815:Young Adult
chemical_list: D002317:Cardiovascular Agents; D014336:Troponin; D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form; D008727:Methotrexate