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

Phase 1

• Conditions: Acute Myocardial Infarction
• Interventions: Other: Autologous Bone marrow mononuclear cells; Other: Placebo control

• Registration Number: NCT01536106
• Lead Sponsor: TotipotentRX Cell Therapy Pvt. Ltd.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2011-07-16
• Study First Submitted QC: 2012-02-17
• Study First Posted: 2012-02-20
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-03
• Last Update Posted: 2013-09-04
• Study Start: 2013-12
• Primary Completion: 2015-01
• Study Completion: 2015-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment	Autologous Bone marrow mononuclear cells	Implantation of bone marrow derived mononuclear cells
Placebo Control	Placebo control	Infusion of autologous peripheral blood

Primary Outcome Measures

Name	Time	Method
Number of adverse events as a measure of safety	12 Months	Feasibility and safety of Intracoronary infusion of autologous BMMNCs processed through intraoperative point of care technology, freedom from arrhythmia's.

Secondary Outcome Measures

Name	Time	Method
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.	12 Months	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.
Major adverse cardiac events (MACE)	12 Months	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.
Quality of life	12 Months	Quality of life assessment is done using short-form 36, Minnesota living with heart failure questionnaire and Seattle Angina Questionnaire

Trial Locations

Locations (3)

Fortis Escorts Heart Institute and Research Centre; 🇮🇳 New Delhi, India

Fortis Flt. Lt. Rajan Dhall Hospital; 🇮🇳 New Delhi, India

CARE Hospitals, Banjara Hills; 🇮🇳 Hyderabad, India