Implantation of Autologous CD133+ Stem Cells in Patients Undergoing CABG
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Heart Failure
- Sponsor
- University Health Network, Toronto
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Freedom from Major Adverse Cardiac Event
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
Following myocardial infarct, cellular therapy is a potential approach to repopulate the injured myocardium, to treat heart failure and restore cardiac function. The purpose of this study is to assess the safety, feasibility and efficacy of intramyocardial delivery of selected autologous CD133+ bone marrow stem cells at the time of coronary artery bypass grafting in patients with chronic ischemic cardiomyopathy.
Detailed Description
CD133+ are well characterized distinct early progenitor group of stem cells that possess high engraftment, pluripotent and angiogenic capacity and proved to be valuable for cardiac repair by promoting neovascularization, inhibition of apoptosis and cardiomyogenesis. The investigators proposed research protocol involves patients with chronic ischemic heart disease and left ventricular dysfunction undergoing coronary artery bypass grafting (CABG). In this phase II clinical trial, prospective, randomized, 2 arm, double-blind, placebo-controlled study, the investigators will assess the safety, feasibility and functional effect of intra-myocardial injection of highly selected autologous CD133+ bone marrow stem cells to placebo.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years, and ≤75 years.
- •Patients with severe chronic ischemic cardiomyopathy manifested by Canadian Cardiovascular Society (CCS) class II or greater angina, and/or New York Heart Association (NYHA) class II or greater dyspnea, AND who have undergone diagnostic coronary angiography demonstrating ≥70% diameter narrowing of at least two major coronary arteries or branches or ≥50% diameter narrowing of the left main coronary artery.
- •Significant left ventricular systolic dysfunction evaluated by echocardiography or LV angiography (LV ejection fraction ≤45% but ≥25%) due to a prior myocardial infarction. This area of left ventricular dysfunction should be akinetic or severely hypokinetic, not dyskinetic or aneurysmal, when assessed by echocardiography or LV angiogram.
- •No contraindications or exclusions (see below).
- •Willingness to participate and ability to provide informed consent.
Exclusion Criteria
- •contraindications to magnetic resonance imaging (MRI) including presence of an implantable cardiac defibrillator (ICD) or permanent pacemaker (PPM), or cases in which it is anticipated that an ICD or PPM will be implanted prior to the 6 month follow-up or claustrophobia (thus precluding performance of follow-up MRI scans).
- •Need for urgent or emergent revascularization.
- •Anticipated for concomitant surgical procedure at the time of CABG (e.g. valve repair or replacement, aneurysm resection, etc.).
- •Hemodynamically unstable patients, as defined by heart rate ≤40/min or ≥100/min, and/or systolic blood pressure \<90 mmHg or ≥200 mmHg, and/or ongoing need for intravenous inotropic or vasopressor medications.
- •Patients with confirmed myocardial infarction within 14 days, and/or rising cardiac biomarker proteins (i.e. CK-MB or troponin), and/or worsening ECG changes.
- •Prior CABG surgery.
- •Stroke within 3 months prior to plan CABG.
- •Immunosuppressive medication (e.g. prednisone, cyclophosphamide, etanercept, etc.)
- •Severe chronic renal insufficiency (serum creatinine ≥ 200 mmol/dl or need for dialysis),liver disease, (diagnosis of cirrhosis, chronic hepatitis, or elevated serum transaminases ≥3 times the upper limit of normal), cerebrovascular disease requiring concomitant carotid endarterectomy, peripheral arterial disease (claudication as the primary factor limiting activity), active non-dermatological malignancy requiring on-going treatment, or any other condition that would place the patient at increased risk for complications during the first 6 months after the procedure in the judgement of the attending cardiologist or cardiac surgeon.
- •Contra-indication to bone marrow aspiration (Thrombocytopenia \<50,000 mm3, INR \>2.0 ).
Outcomes
Primary Outcomes
Freedom from Major Adverse Cardiac Event
Time Frame: 6 months
cardiac death, myocardial infarct, repeat coronary bypass grafting or percutaneous intervention of bypassed artery.
Freedom from major arrhythmia
Time Frame: 6 months
sustained ventricular tachycardia or survived sudden death.
Secondary Outcomes
- Device performance end point(baseline)
- Global ventricular function assessed by echocardiographic measures of ejection fraction(6 months)
- Relief of symptom severity after CABG surgery(6 months)
- Quality of Life after CABG surgery(6 months)
- Regional myocardial perfusion and function assessed by magnetic resonance scans(6 months)