The Melatonin Adjunct in the Acute myocaRdial Infarction Treated With Angioplasty (MARIA)

• Major cardiac events: Death, sustained ventricular arrhythmias, resuscitation from cardiac arrest, cardiogenic shock, heart failure, major bleedings, stroke, need for revascularization, recurrent ischemia, re-infarctions and re-hospitalization. [ Time Frame: within the first year ] [ Designated as safety issue: Yes ]
• Changes in left ventricular ejection fraction evaluated by cardiac magnetic resonance [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]

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.

Study design: The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial is a 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 cardiac magnetic resonance 5-7 days post-reperfusion. Other secondary end points will be the clinical events occurring within the first year: death, sustained ventricular arrhythmias, resuscitation from cardiac arrest, cardiogenic shock, heart failure, major bleedings , stroke, need for revascularization, recurrent ischemia, re-infarctions and rehospitalization; and changes in left ventricular ejection fraction from baseline to 4 months of follow-up.

Implications: 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.

• Experimental: A: Melatonin
  Melatonin: intravenous infusion and intracoronary bolus
  Intervention: Drug: melatonin
• Placebo Comparator: B: Placebo of melatonin
  Placebo: intravenosus infusion and intracoronary bolus
  Intervention: Drug: melatonin

Inclusion Criteria:

1. Aged between 18 and 75 years.
2. Having experienced continuous ischemic (cardiac) symptoms for at least 20 minutes.
3. Having onset of symptoms of qualifying acute myocardial infarction within the past 6 hours and be expected to undergo primary angioplasty.

4. Having an electrocardiogram indicative of an acute ST segment -elevation myocardial infarction showing:

   > 2 mm ST segment elevation in 2 anterior or lateral leads; or > 2 mm ST segment elevation in 2 inferior leads coupled with ST depression in 2 contiguous anterior leads for a total ST deviation of > 8 mm; or new left bundle branch block with at least 1 mm concordant ST elevation.

5. Being willing to provide informed consent (informed consent may be provided by a legally authorized representative if the patient is not able to provide it according to local ethical standards).
6. Being willing and able to be followed for at least 3 months for evaluation.

Exclusion Criteria:

A patient will be ineligible for study entry if he/she meets any of the following criteria:

1. prehospital thrombolysis,
2. Killip class IV on admission,
3. known history of prior myocardial infarction,
4. known history of renal failure,
5. history of severe allergic reaction,
6. history of autoimmune diseases,
7. pregnancy,
8. severe concurrent illness with reduced short-term prognosis,
9. inability to give informed consent and
10. participation in another study within the past 30 days.