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

Myocardial Ischemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00402506
• Other study ID #: 06004
• Status: Completed
• Phase: Phase 3
• First received: November 20, 2006
• Last updated: November 15, 2007
• Start date: November 2006
• Est. completion date: September 2007

Study information

• Verified date: November 2007
• Source: Medicure
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3000
• Est. completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Bypass Graft Surgery
• Coronary Artery Disease
• Myocardial Ischemia
• Reperfusion Injury

Intervention

Drug:
• (MC-1) Pyridoxal 5'-phosphate

Locations

Country	Name	City	State
Canada	Montreal Heart Institute	Montreal	Quebec
United States	Duke Clinical Research Institute	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Medicure

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Kandzari DE, Labinaz M, Cantor WJ, Madan M, Gallup DS, Hasselblad V, Joseph D, Allen A, Green C, Hidinger KG, Krucoff MW, Christenson RH, Harrington RA, Tcheng JE. Reduction of myocardial ischemic injury following coronary intervention (the MC-1 to Eliminate Necrosis and Damage trial). Am J Cardiol. 2003 Sep 15;92(6):660-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	combined incidence of cardiovascular death or nonfatal myocardial infarction on days up to and including post-operative day (POD) 30
Secondary	length of hospital stay for index hospitalization
Secondary	length of stay in intensive care unit (ICU) or coronary care unit (CCU) for index hospitalization
Secondary	incidence of cardiovascular death up to and including POD 90