title: A unicenter, randomized, double-blind, parallel-group, placebo-controlled study of Melatonin as an Adjunct in patients with acute myocaRdial Infarction undergoing primary Angioplasty The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial: study design and rationale.
abstract: BACKGROUND
  Experimental studies have documented the beneficial effects of the endogenously produced antioxidant, melatonin, in reducing tissue damage and limiting cardiac pathophysiology in models of experimental ischemia-reperfusion. Melatonin confers cardioprotection against ischemia-reperfusion injury most likely through its direct free radical scavenging activities and its indirect actions in stimulating antioxidant enzymes. These actions of melatonin permit it to reduce molecular damage and limit infarct size in experimental models of transient ischemia and subsequent reperfusion.
  
  
  METHODS
  The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial is an unicenter, prospective, randomized, double-blind, placebo-controlled, phase 2 study of the intravenous administration of melatonin. The primary efficacy end point of this study is to determine whether melatonin treatment reduces infarct size determined by the cumulative release of alpha-hydroxybutyrate dehydrogenase (area under the curve: 0 to 72 h). Other secondary end points will be the clinical events occurring within the first 90 days: death, sustained ventricular arrhythmias, resuscitation from cardiac arrest, cardiogenic shock, heart failure, major bleedings, stroke, need for revascularization, recurrent ischemia, re-infarctions and rehospitalization.
  
  
  CONCLUSIONS
  The MARIA trial tests a novel pharmacologic agent, melatonin, in patients with acute myocardial infarction and the hypothesis that it will confer cardioprotection against ischemia-reperfusion injury. If successful, the finding would support the use of melatonin in therapy of ischemic-reperfusion injury of the heart.
authors.affiliation: Department of Cardiology, Coronary Care Unit, University Hospital of Canarias, Ofra s/n La Cuesta E-38320, Tenerife, Spain. adrvdg@hotmail.com
authors.forename: Alberto
authors.initials: A
authors.lastname: Dominguez-Rodriguez
authors.forename: Pedro
authors.initials: P
authors.lastname: Abreu-Gonzalez
authors.forename: Martín J
authors.initials: MJ
authors.lastname: Garcia-Gonzalez
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Kaski
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.forename: Alejandro
authors.initials: A
authors.lastname: Jimenez-Sosa
mesh_terms: D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000975:Antioxidants / Q000008:administration & dosage*; D019540:Area Under Curve; D002423:Cause of Death; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006884:Hydroxybutyrate Dehydrogenase / Q000097:blood; D007262:Infusions, Intravenous; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D010359:Patient Readmission; D011446:Prospective Studies; D012008:Recurrence; D012107:Research Design
chemical_list: D000975:Antioxidants; C035749:2-hydroxybutyrate dehydrogenase; D006884:Hydroxybutyrate Dehydrogenase; D008550:Melatonin