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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Coronary Artery Bypass Graft Surgery, Myocardial Ischemia, Reperfusion Injury

Intervention / Treatment
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* Drug: (MC-1) Pyridoxal 5'-phosphate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: (MC-1) Pyridoxal 5'-phosphate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| combined incidence of cardiovascular death or nonfatal myocardial infarction on days up to and including post-operative day (POD) 30 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronary, surgery, ischemia, reperfusion injury, cardiac, heart, neurological, cardiopulmonary bypass, cardioprotection, myocardium, myocardial, myocardial revascularization