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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Fundación Canaria Rafael Clavijo para la Investigación Biomédica
Sponsor:
Information provided by (Responsible Party):
Alberto Dominguez-Rodriguez, MD, PhD, FESC, Fundación Canaria Rafael Clavijo para la Investigación Biomédica
ClinicalTrials.gov Identifier:
NCT00640094
First received: March 12, 2008
Last updated: September 26, 2014
Last verified: September 2014
  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 an unicentric, 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.


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: A Unicentric, 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:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 272
Study Start Date: May 2013
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A 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 microMolar melatonin during 150 minutes with a drip rate of 4.2 ml/min.

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
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

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

Locations
Spain
Hospital General Universitario Santa Lucia Active, not recruiting
Cartagena, Murcia, Spain, 30202
University Hospital of Canarias Recruiting
La Laguna, Tenerife, Spain, E-38320
Contact: Alberto Dominguez-Rodriguez, MD, PhD, FESC    +34 922 679040    adrvdg@hotmail.com   
Sub-Investigator: Pedro Abreu-Gonzalez, PhD         
Sub-Investigator: Juan Carlos Kaski, MD, DM, DSc, FRCP, FESC, FACC.         
Sub-Investigator: Russel J Reiter, PhD         
Hospital Universitario Marqués de Valdecilla Recruiting
Santander, Spain
Contact: José M. de la Torre Hernández, PhD       he1thj@humv.es   
Principal Investigator: José M. de la Torre Hernández, PhD         
Sponsors and Collaborators
Alberto Dominguez-Rodriguez, MD, PhD, FESC
Investigators
Principal Investigator: Alberto Dominguez-Rodriguez, MD, PhD, FESC
  More Information

Publications:
Responsible Party: Alberto Dominguez-Rodriguez, MD, PhD, FESC, 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: September 26, 2014
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
Cardiovascular Diseases
Heart Diseases
Ischemia
Myocardial Ischemia
Necrosis
Pathologic Processes
Vascular Diseases
Melatonin
Antioxidants
Central Nervous System Agents
Central Nervous System Depressants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014