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.
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.
Dominguez-Rodriguez
Alberto
A
Department of Cardiology, Coronary Care Unit, University Hospital of Canarias, Ofra s/n La Cuesta E-38320, Tenerife, Spain. adrvdg@hotmail.com
Abreu-Gonzalez
Pedro
P
Garcia-Gonzalez
Martín J
MJ
Kaski
Juan Carlos
JC
Reiter
Russel J
RJ
Jimenez-Sosa
Alejandro
A
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
D000975:Antioxidants; C035749:2-hydroxybutyrate dehydrogenase; D006884:Hydroxybutyrate Dehydrogenase; D008550:Melatonin