A Safety and Efficacy Study to Confirm the Cardioprotective Effects of MC-1 in Patients Undergoing High-Risk CABG

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00402506
Recruitment Status : Completed
First Posted : November 22, 2006
Last Update Posted : November 16, 2007
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Brief Summary:
The purpose of this study is to determine the effect of MC-1 on the combined incidence of cardiovascular death and nonfatal myocardial infarction (MI) up to and including 30 days following coronary artery bypass graft (CABG) surgery compared with placebo.

Condition or disease Intervention/treatment Phase
Coronary Artery Bypass Graft Surgery Myocardial Ischemia Reperfusion Injury Drug: (MC-1) Pyridoxal 5'-phosphate Phase 3

Detailed Description:

Coronary artery bypass grafting (CABG) effectively relieves angina, results in longer survival, and a better quality of life in specific subgroups of patients with obstructive coronary artery disease. Due to the high incidence of coronary artery disease worldwide, as well as the effectiveness of the surgical procedure, CABG surgery makes up one of the top ten most frequently performed procedures in North America and Europe. In the United States it is estimated that approximately 467,000 CABG procedures were performed in 2003.

Despite the benefits of CABG surgery, patients undergoing these procedures may also suffer serious adverse outcomes including operative mortality, myocardial infarction, unstable angina, ventricular failure, life-threatening arrhythmia, renal insufficiency, and stroke. Some of the proposed causes of cardiovascular morbidity and mortality after CABG include perioperative ischemia, inadequate myocardial protection and reperfusion injury. The impact of these serious complications is significant. Incidence rates of death and MI following CABG surgery range from 5% to 12% depending on risk status. Results from large clinical trials have recently demonstrated the importance of neurologic deficits as a problematic outcome of CABG. These deficits include memory impairment, psychomotor, visuospatial, attention and language abilities as measured by neuropsychological testing as well as sensorimotor abnormalities associated with stroke.

MC-1 is a naturally occurring metabolite of vitamin B6. Evidence from pre-clinical and clinical studies suggests that MC-1 protects the heart from ischemic damage and ischemia-reperfusion injury. This trial will assess the cardioprotective effects of MC-1 compared to placebo in patients undergoing high-risk CABG surgery.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: MEND-CABG II: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Cardioprotective Effects of MC-1 in Patients Undergoing High-Risk CABG Surgery
Study Start Date : November 2006
Actual Study Completion Date : September 2007

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. combined incidence of cardiovascular death or nonfatal myocardial infarction on days up to and including post-operative day (POD) 30

Secondary Outcome Measures :
  1. length of hospital stay for index hospitalization
  2. length of stay in intensive care unit (ICU) or coronary care unit (CCU) for index hospitalization
  3. incidence of cardiovascular death up to and including POD 90

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must be scheduled to undergo CABG surgery (during routine scheduling times) and had planned to use cardiopulmonary bypass.
  • Provide informed consent
  • Age ≥ 18
  • Male patients, or female patients not of childbearing potential or who have had a negative pregnancy test and are practicing adequate contraception
  • Patients must be considered at high risk for subsequent myocardial complications defined as meeting 2 or more of the following:

    • Age ≥ 65
    • Current or recent smoker (within last 6 months)
    • History of diabetes mellitus requiring treatment other than diet
    • Evidence of left ventricular dysfunction or congestive heart failure assessed by:

      • Ejection fraction (EF) ≤ 45%
      • Left ventricular end diastolic pressure (LVEDP) or pulmonary wedge pressure (PWP) ≥ 20 mm Hg
      • Pulmonary edema by chest X-ray
      • Cardiothoracic ratio > 50% on chest X-ray
    • History of a previous non-disabling stroke, transient ischemic attack, or carotid endarterectomy
    • Urgent CABG intervention defined as the need to stay in the hospital (although patient may be operated on within a normal scheduling routine)
    • History of a myocardial infarction that occurred more than 48 hours but less than 6 weeks prior to CABG surgery
    • Prior peripheral artery surgery or angioplasty
    • Moderate renal dysfunction defined as creatinine clearance ≥ 30 ml/min, but < 60 ml/min
    • Presence of at least one asymptomatic carotid artery stenosis (≥ 50%) either in one or two carotid arteries

Exclusion Criteria:

  • Planned associated valve surgery or concurrent carotid endarterectomy
  • Planned aortic dissection repair or aortic root reconstruction
  • Screening visit occurring less than 4 hours before scheduled CABG surgery
  • Mini-Mental State Examination (MMSE) score less than 24 at the screening visit
  • Current cardiogenic shock, acute left ventricular rupture, ventricular septal rupture, or papillary muscle rupture
  • Uncontrolled diabetes defined as fasting serum blood glucose value equal to or greater than 24 mmol/L (432 mg/dl) at the time of screening (if fasting serum blood glucose not obtained at screening, values obtained within 30 days prior to screening visit may be used)
  • Myocardial infarction occurring < 48 hours prior to planned CABG surgery
  • Severe renal dysfunction defined as an estimated creatinine clearance value of < 30 ml/min or nephrotic syndrome at screening (or measured creatinine clearance value obtained within 30 days prior to screening visit)
  • History of liver cirrhosis, chronic active hepatitis (known positive serum test within 6 months of enrolment), or severe liver dysfunction; or liver transaminase ≥ 3 times upper limit of normal (ULN) at screening (or obtained within 30 days prior to screening visit).
  • History of malignancy during last 5 years except for basal cell carcinoma
  • Planned surgery for atrial fibrillation
  • Planned associated transmyocardial revascularization
  • Planned associated ventricular remodeling
  • Pregnancy or potential for pregnancy
  • Any medical or psychiatric condition which, in the opinion of the investigator, makes the patient an unsuitable candidate for the study
  • Significant, ongoing alcohol or drug abuse
  • Participation in any other investigational drug or device study within 30 days of randomization

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00402506

United States, North Carolina
Duke Clinical Research Institute
Durham, North Carolina, United States, 27705
Canada, Quebec
Montreal Heart Institute
Montreal, Quebec, Canada, H1T 1C8
Sponsors and Collaborators
Principal Investigator: Michel Carrier, MD Montreal Heart Institute
Principal Investigator: Robert A Harrington, MD Duke Clinical Research Institute

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00402506     History of Changes
Other Study ID Numbers: 06004
First Posted: November 22, 2006    Key Record Dates
Last Update Posted: November 16, 2007
Last Verified: November 2007

Keywords provided by Medicure:
reperfusion injury
cardiopulmonary bypass
myocardial revascularization

Additional relevant MeSH terms:
Myocardial Ischemia
Coronary Artery Disease
Reperfusion Injury
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Coronary Disease
Arterial Occlusive Diseases
Postoperative Complications
Pyridoxal Phosphate
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs