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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Alberto Domínguez Rodríguez, Fundación Canaria Rafael Clavijo para la Investigación Biomédica
ClinicalTrials.gov Identifier:
NCT00640094
First received: March 12, 2008
Last updated: July 22, 2016
Last verified: July 2016
  Purpose

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.


Condition Intervention Phase
Acute Myocardial Infarction
Drug: melatonin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-blind, Parallel-group, Placebo-controlled Study of Melatonin as an Adjunct in Patients With Acute myocaRdial Infarction Undergoing Primary Angioplasty

Resource links provided by NLM:


Further study details as provided by Fundación Canaria Rafael Clavijo para la Investigación Biomédica:

Primary Outcome Measures:
  • Infarct size [ Time Frame: 5-7 days post-reperfusion ] [ Designated as safety issue: Yes ]
    The primary efficacy end point in this study is to determine whether melatonin treatment reduces infarct size (percentage of total myocardial necrotic mass) by cardiac magnetic resonance


Secondary Outcome Measures:
  • 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 ]

Enrollment: 272
Study Start Date: May 2013
Estimated Study Completion Date: November 2016
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: Melatonin
Melatonin: intravenous infusion and intracoronary bolus
Drug: melatonin
Patients will receive a total intravenous melatonin dose of 12 mg + intracoronary melatonin dose of 2 mg. The intravenous dose will be distributed in a volume of 50 ml of a isotonic and sterile solution and administered by intravenous infusion during 60 minutes. The intracoronary dose will be distributed in a volume of 10 ml of a isotonic and sterile solution and administered as a bolus.
Other Name: 5-methoxy-tryptamine
Placebo Comparator: B: Placebo of melatonin
Placebo: intravenosus infusion and intracoronary bolus
Drug: melatonin
Patients will receive a total intravenous melatonin dose of 12 mg + intracoronary melatonin dose of 2 mg. The intravenous dose will be distributed in a volume of 50 ml of a isotonic and sterile solution and administered by intravenous infusion during 60 minutes. The intracoronary dose will be distributed in a volume of 10 ml of a isotonic and sterile solution and administered as a bolus.
Other Name: 5-methoxy-tryptamine

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

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00640094

Locations
Spain
Hospital General Universitario Santa Lucia
Cartagena, Murcia, Spain, 30202
University Hospital of Canarias
La Laguna, Tenerife, Spain, E-38320
Hospital Universitario Marqués de Valdecilla
Santander, Spain
Sponsors and Collaborators
Alberto Domínguez Rodríguez
Investigators
Principal Investigator: Alberto Dominguez-Rodriguez, MD, PhD, FESC
  More Information

Publications:
Responsible Party: Alberto Domínguez Rodríguez, MD, PhD, FESC, Fundación Canaria Rafael Clavijo para la Investigación Biomédica
ClinicalTrials.gov Identifier: NCT00640094     History of Changes
Other Study ID Numbers: 2005-000821-49 
Study First Received: March 12, 2008
Last Updated: July 22, 2016
Health Authority: United States: Food and Drug Administration
Spain: Ethics Committee
Spain: Ministry of Health
Spain: Spanish Agency of Medicines

Keywords provided by Fundación Canaria Rafael Clavijo para la Investigación Biomédica:
Melatonin
Acute myocardial infarction
Primary angioplasty

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Melatonin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants

ClinicalTrials.gov processed this record on July 28, 2016