Retrograde Application of Bone Marrow Aspirate Concentrate

Study Overview
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Brief Summary
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The aim of our prospective randomised study is to assess the efficacy of the retrograde application of non-selected bone marrow autologous cells concentrate (BMAC) in patients with heart failure with reduced ejection fraction of left ventricle (HFREF) of ischemic aetiology. The evaluated preparation is concentrated BMAC, obtained using Harvest SmartPReP2 technology.

Detailed Description
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Our assumption is that non-selected BMAC administrations will lead to improvements in the left ventricular ejection fraction (LV EF), the left ventricular end-systolic and end-diastolic diameters and volumes (measured with magnetic resonance imaging) compared to standard heart failure therapy. Furthermore, it will be associated with improved exercise tolerance in the six-minute corridor walk test and an improvement in the life quality of patients without increasing the incidence of severe ventricular arrythmias.

Official Title
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Retrograde Application of Bone Marrow Aspirate Concentrate (BMAC) Through Coronary Sinus in Patients With Congestive Heart Failure of Ischemic Etiology

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: BMAC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with chronic heart failure and left ventricular ejection fraction ≤ 40% with coronary artery disease and with symptoms of heart failure in the NYHA class ≥ 3 on standard heart failure therapy for 3 months and in a stabilised state for at least 1 month Age ≥18 years Informed, written consent by the patient Ability to comply fully with the study protocol Negative pregnancy test (and effective contraception) in women with childbearing potential Exclusion Criteria: Previous bone marrow disease (especially myelodysplastic syndrome or non-Hodgkin's lymphoma) Acute myocardial infarction ˂ 1 week Active infection or antibiotics treatment ˂ 1 week Previous malingant ventricular arrhythmias without cardioverter-defibrilator (ICD) implantation Anemia (HTC≤28%), leukocythosis (≥ 14.000/mm3) or thrombocytopenia (≤50.000/mm3) Previous bleeding diathesis Need for hematopoietic growth factor treatment (e.g. erythropoetin, G-CSF) Impossibility of aspiration 240ml of bone marrow Hepathopathy or cirrhosis (bilirubin, ALT or AST ≥ 2,5x upper limit of normal) Terminal renal insufficiency or haemodyalysis Uncontrolled hypertension Need for high dose (> 7.5mg/day) corticotherapy within the next 6 months Inability to stop anticoagulation therapy (>72 hours) before bone marrow aspiration Known malignancies requiring actino or chemotherapy, or previous actinotherapy Patients with a BMI >40 Known allergy to contrast agents Other comorbidities with a life expectancy of 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Bone marrow autologous cells concentrate (BMAC)<br>retrograde administration on non-selected BMAC via coronary sinus | Drug: BMAC<br>* retrograde administration on non-selected BMAC via coronary sinus<br>|
| Placebo Comparator: Control<br>standard treatment o heart failure | Drug: BMAC<br>* retrograde administration on non-selected BMAC via coronary sinus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular end-systolic diameter (LVESd) | Left ventricular end-systolic diameter | 12 month | 
| Left ventricular end-systolic volume (LVESV) | Left ventricular end-systolic volume | 12 month | 
| Left ventricular end-diastolic diameter (LVEDd) | Left ventricular end-diastolic diameter | 12 month | 
| Left ventricular end-diastolic volume (LVEDV) | Left ventricular end-diastolic volume | 12 month | 
| ejection fraction of left ventricle (EF LV) | ejection fraction of left ventricle | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| corridor walk test | walk distance in 6 min corridor walk test | 12 month | 
| QoL | Quality of patients´ life using the Minnesota questionnaire | 12 month |