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

This study has been completed.
Sponsor:
Information provided by:
Medicure
ClinicalTrials.gov Identifier:
NCT00402506
First received: November 20, 2006
Last updated: November 15, 2007
Last verified: November 2007
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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

Resource links provided by NLM:


Further study details as provided by Medicure:

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

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

Estimated Enrollment: 3000
Study Start Date: November 2006
Study Completion Date: September 2007
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00402506

Locations
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
Medicure
Investigators
Principal Investigator: Michel Carrier, MD Montreal Heart Institute
Principal Investigator: Robert A Harrington, MD Duke Clinical Research Institute
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00402506     History of Changes
Other Study ID Numbers: 06004
Study First Received: November 20, 2006
Last Updated: November 15, 2007
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Medicure:
coronary
surgery
ischemia
reperfusion injury
cardiac
heart
neurological
cardiopulmonary bypass
cardioprotection
myocardium
myocardial
myocardial revascularization

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

ClinicalTrials.gov processed this record on October 20, 2014