Official 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”

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 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.

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2009

See article for more detailed description: Contemporary Clinical Trials 28 (2007) 532-539

Intervention(s) in this Clinical Trial

• Drug: melatonin
  • Patients will receive a total intravenous melatonin dose of 11.61 mg (approximately 166 microgram/kg) or placebo. The dose will be distributed in a volume of 500 ml of a isotonic and sterile solution of 100 microM melatonin during 150 minutes with a drip rate of 4.2 ml/min.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A

Primary Measures

• The primary efficacy end point in this study is to determine whether melatonin treatment reduces of infarct size as determined by the cumulative release of alpha-hydroxybutyrate dehydrogenase.
  • Time Frame: within the first 72 hours
    Safety Issue?: Yes

Secondary Measures

• 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 90 days
    Safety Issue?: Yes

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-elevation myocardial infarction showing:
• > 2 mm ST elevation in 2 anterior or lateral leads; or > 2 mm ST 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Fundación Canaria Rafael Clavijo para la Investigación Biomédica

Overall Clinical Trial Officials and Contacts

Alberto Dominguez-Rodriguez, MD, PhD, FESC Principal Investigator Unaffiliated.  

Overall Contact: Alberto Dominguez-Rodriguez, MD, PhD, FESC +34 922 679030 adrvdg@hotmail.com

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00640094

Study ID Number: 2005-000821-49

ClinicalTrials.gov Identifier: NCT00640094

Health Authority: United States: Food and Drug Administration