Pyridoxal and Pyridoxal Phosphate and (MC-1) Pyridoxal-5'-phosphate in Myocardial Ischemia and Reperfusion Injury and Coronary Artery Bypass Graft Surgery - Clinical Trials Registry

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Drug: (MC-1) Pyridoxal-5'-phosphate

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 over 700,000 CABG procedures are performed per year.

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 sensori-motor abnormalities associated with stroke.

MC-1 is a naturally occurring small molecule. 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 effects of MC-1 compared to placebo on cardiovascular and neurological events following CABG surgery.

Study Type

Interventional

Enrollment

900

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Canada
- Quebec
  - Montreal, Quebec, Canada, H1T 1C8
    - Montreal Heart Institute
United States
- North Carolina
  - Durham, North Carolina, United States, 27710-7510
    - Duke University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients must be scheduled to undergo CABG surgery (during routine scheduling times) planned to use cardiopulmonary bypass

Patients must be considered at high risk for subsequent neurological or myocardial complications defined as meeting 2 or more of the following:

Age >65
Current smoker
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 greater than or equal to 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 by creatinine ≥ 133 micromol/L (1.5 mg/dL), but < 250 micromol/L (2.8 mg/dL)
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
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 a serum creatinine value ≥ 250 micromol/L (2.8 mg/dL) or nephritic syndrome at screening (or obtained within 30 days prior to screening visit)
History of liver cirrhosis, chronic active hepatitis, or severe liver dysfunction , or liver transaminase ≥3 times 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
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
History of alcohol or drug abuse within the past year
Participation in any other investigation drug or device study within 30 days of randomization

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Combined incidence of cardiovascular death, nonfatal myocardial infarction and nonfatal cerebral infarction on days up to and including post-operative day 30.

Secondary Outcome Measures

Outcome Measure
Combined incidence of cardiovascular death, nonfatal myocardial infarction and nonfatal cerebral infarction up to and including post-operative day (POD) 90
Incidence of cardiovascular death up to and including POD 4, POD 30, POD 90
Incidence of nonfatal myocardial infarction up to and including POD 4, POD 30, POD 90
Incidence of all cause morality up to and including POD 4, POD 30, POD 90
Global disability as measured by the Modified Rankin scale at POD 30 and POD 90
MMSE score at POD 30 and POD 90
Among patients with a confirmed cerebral infarction, severity of stroke as measured by the National Institutes of Health Stroke Scale (NIHSS) at the time of stroke diagnosis and at subsequent study visits up to and including POD 90
Psychometric testing results as measured by a short battery of tests at POD 4, POD 30 and POD 90 on a subset of approximately 150 volunteers per treatment arm
CK-MB AUC (0-24 hours)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medicure

Investigators

Principal Investigator: Jean-Claude Tardif, MD, FRCPC, FACC, Montreal Heart Institute Research Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2004

Study Completion

October 1, 2005

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria