Rapid Delivery of Autologous Bone Marrow Derived Stem Cells in Acute Myocardial Infarction Patients.

Study Overview
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Brief Summary
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The primary objective of the study is to determine the feasibility and safety of intracoronary administration of autologous bone marrow derived mononuclear cell product in patients at risk for clinically significant cardiac dysfunction following AMI. The secondary objective of the study is to assess the effect on cardiac function and infarct region perfusion. A concurrent placebo control patient group meeting eligibility but not receiving autologous bone marrow derived stem cells will be evaluated similar to the treated group to assess the rate of significant spontaneous improvement in cardiac function.

Detailed Description
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Emerging evidence indicate that progenitor stem cells derived from bone marrow can be used to improve cardiac function in acute myocardial infarction patients. There is a great potential for stem cell therapy, using a variety of cell precursors to contribute to new blood vessel formation and muscle preservation in the myocardial infarct zone. The administration of cells via an infusion through the infarct related artery appears to be feasible and result in a clinical effect in some studies. Across the globe AMI is the leading cause of morbidity and mortality. This cannot be prevented by optimal standard therapies i.e. balloon or stent dilation of the infarct vessels. The study is a double blind, placebo controlled, randomized, multicenter trial. Male or female patients between 18-75 years with first incidence of Acute Myocardial Infarction(AMI) and LVEF less than or equal to 40% are included in the study. Patients who have undergone successful percutaneous intervention (PCI) within ≤ 24 hours after onset of symptoms (PTCA/stent) or / and Thrombolysed patients having TIMI-3 flow are eligible to take part in the study. A total of 30 subjects will be recruited and randomly assigned to receive concentrated BMMNC or placebo. All patients will undergo bone marrow aspiration within 3-10 days from the index event(infarction). Bone Marrow(BM) will be processed utilizing point of care technology. Following cell processing, the concentrated BMMNC or placebo control is infused directly into the infarct related artery using the stop flow method. Clinical follow up for all the subjects at 1,30, 60, 90, 180 and 360 days will be performed from the day of the procedure, with primary and secondary end points evaluated for both study arms.

Official Title
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Intracoronary Infusion of Concentrated Autologous Bone Marrow Mononuclear Cells in Acute Myocardial Infarction Patients Utilizing a Novel Point-of-Care Device for Rapid-Delivery of Stem Cells (AMIRST)

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Other: Autologous Bone marrow mononuclear cells
* Other: Placebo control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female of age 18 - 75 years Incidence of first myocardial infarction Acute STEMI with LV hypokinesia involving anteroseptal, lateral or inferior walls LVEF < 40% pre-intervention Successful percutaneous intervention (PCI) within ≤ 24 hours after onset of symptoms (PTCA/stent) or / and Thrombolysed patients having TIMI-3 flow. Written informed consent Exclusion Criteria: Multi-vessel coronary disease requiring surgical intervention (CABG) or left main coronary artery disease > 50% blockage Previous history of CABG Pulmonary edema Cardiogenic shock Myocarditis Renal or hepatic dysfunction Hematologic disease General Exclusion Criteria: Alcohol or drug dependency, active or uncontrolled acute myocarditis HIV, HBV, or HCV infections Evidence of malignant or hematological diseases Metal implants of any kind Claustrophobia Renal insufficiency History of bleeding disorder Anemia (haemoglobin <8.5mg/dl) Platelet count <100,000/ml

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Implantation of bone marrow derived mononuclear cells | Other: Autologous Bone marrow mononuclear cells<br>* Intracoronary administration of concentrated BMMNC on the same day of BM aspiration using point of care technology.<br>* Other names: BMMNC treatment group;|
| Placebo Comparator: Placebo Control<br>Infusion of autologous peripheral blood | Other: Placebo control<br>* Intracoronary infusion of autologous peripheral blood.<br>* Other names: Placebo control group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events as a measure of safety | Feasibility and safety of Intracoronary infusion of autologous BMMNCs processed through intraoperative point of care technology, freedom from arrhythmia's. | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the global Left Ventricular Ejection Fraction(LVEF), LV volumes-End Systolic Volume (ESV) and End Diastolic Volume (EDV), infarct size, myocardial mass, myocardial viability and regional wall motion abnormalities. | Changes in the global Left Ventricular Ejection Fraction(LVEF), LV volumes-End Systolic Volume (ESV) and End Diastolic Volume (EDV), infarct size, myocardial mass, myocardial viability and regional wall motion abnormalities measured by Cardiac MRI and assessed by central Core lab. | 12 Months | 
| Major adverse cardiac events (MACE) | MACE was defined as the composites of any cause of death, myocardial infarction, revascularization of the target vessel, re-hospitalization for heart failure, and life-threatening arrhythmia. | 12 Months | 
| Quality of life | Quality of life assessment is done using short-form 36, Minnesota living with heart failure questionnaire and Seattle Angina Questionnaire | 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cell therapy, Bone marrow stem cells, cardiac cell therapy