Direct Endomyocardial Injection of Autologous Bone Marrow Cells to Treat Ischaemic Heart Failure

Study Overview
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Brief Summary
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The purpose of this study is to determine whether direct endomyocardial injection of autologous bone marrow cells is effective for enhancement of neovascularisation in patients with ischaemic heart failure.

Detailed Description
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Coronary artery disease (CAD) remains to be one of the leading causes of mortality and morbidity worldwide. Despite the optimal use of anti-anginal medications and coronary revascularization, a large number of patients with CAD suffer from severe symptoms with disabling angina and heart failure (HF). Experimental and pilot clinical studies provided evidence of the safety and potential efficacy of a strategy of intramyocardial transplantation of autologous bone marrow (BM) cells for neovascularisation of chronically ischemic myocardium. Nevertheless, the possible potent placebo effect on symptoms observed in these pilot studies highlights the need for a randomized, placebo-controlled group to prove the clinical efficacy of cell based angiogenic therapy for treatment of severe CAD.

Official Title
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Double-blind Placebo Controlled Trial on Direct Endomyocardial Injection of Autologous Bone Marrow Cells for Enhancement of Neovascularization in Patients With Ischaemic Heart Failure (END-HF)

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Procedure: Endomyocardial Injection of Autologous Bone Marrow Cells
* Procedure: Endomyocardial Injection of Plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years old Canadian cardiovascular (CV) Class II-IV angina and/or NYHA class II-III HF symptoms Received stable and best cardiac medical therapy including long-acting nitrates, beta-blocker, and angiotensin-converting enzyme inhibitors without control of symptoms. Not suitable for conventional revascularization by their referring cardiologist. LVEF <40% by echocardiography. Recent coronary angiogram (within the last 6 months) to document the coronary anatomy and insure the presence of CAD that is not amenable to standard revascularization procedures. creatinine less than 250mmol/L, normal liver function, and normal blood count: WBC, granulocytes; platelet count, Hb. Reversible perfusion defect on single photon emission computed tomography (SPECT) Able to walk on treadmill Hemodynamically stable Subject is willing to comply with specified follow-up evaluations. All patients give written informed consent. Exclusion Criteria: Atrial fibrillation History of syncope or major ventricular arrhythmias such as sustained ventricular tachycardia or ventricular fibrillation Severe valve disease Aortic or mitral valve prosthesis History of cancer in last 5 years Acute or chronic active sepsis, including HIV positive; hepatitis B or C positive Left ventricular wall thickness less than 8 mm in the target territory Left ventricular thrombus and/or spontaneous echo-contrast in the LV detected by echocardiography or LV aneurysm Severe aorto-femoral-iliac disease Recent heart attack within the last 30 days Hypertrophic or restrictive cardiomyopathy Severe co-morbidity associated with a reduction in life expectancy of less than 1 year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous bone marrow cells<br> | Procedure: Endomyocardial Injection of Autologous Bone Marrow Cells<br>* Endomyocardial Injection of Autologous Bone Marrow Cells<br>* Other names: END-HF;|
| Placebo Comparator: Plasma<br> | Procedure: Endomyocardial Injection of Plasma<br>* Endomyocardial Injection of Plasma<br>* Other names: END-HF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI ejection fraction |  | MRI ejection fraction changed from baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in exercise duration and MVO2 using standardized treadmill testing(modified Bruce protocol) from baseline to 6 months |  | Baseline to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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END-HF