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

Sponsor

Medicure (Industry)

Overall Status

Completed

CT.gov ID

NCT00402506

Collaborator

(none)

3,000

Enrollment

Locations

Duration (Months)

1500

Patients Per Site

150.2

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Anticipated 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 :

Nov 1, 2006

Actual Study Completion Date :

Sep 1, 2007

Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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