Clinical trial NCT01536106: Rapid Delivery of Autologous Bone Marrow Derived Stem Cells in Acute Myocardial Infarction Patients.
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Acute Myocardial Infarction
Keywords: Cell therapy, Bone marrow stem cells, cardiac cell therapy
Lead sponsor: TotipotentRX Cell Therapy Pvt. Ltd.
Sponsor class: INDUSTRY
Collaborators: name: TotipotentRX Corporation
First posted: 2012-02-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of adverse events as a measure of safety
timeFrame: 12 Months
Secondary outcomes:
measure: 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.
timeFrame: 12 Months
measure: Major adverse cardiac events (MACE)
timeFrame: 12 Months
measure: Quality of life
timeFrame: 12 Months
Other outcomes:
Locations:
city: Hyderabad
country: India
facility: CARE Hospitals, Banjara Hills
city: New Delhi
country: India
facility: Fortis Escorts Heart Institute and Research Centre
city: New Delhi
country: India
facility: Fortis Flt. Lt. Rajan Dhall Hospital
Study officials:
affiliation: TotipotentRX Cell Therapy Pvt. Ltd.
name: Venkatesh Ponemone, PhD
role: STUDY_DIRECTOR
affiliation: TotipotentRX Cell Therapy Pvt. Ltd.
name: Kenneth Harris, MS
role: STUDY_CHAIR
affiliation: Fortis Escorts Heart Institute and Research Centre
name: Ashok Seth, FRCP, FACC
role: PRINCIPAL_INVESTIGATOR
affiliation: Fortis Flt. Lt. Rajan Dhall Hospital
name: Upendra Kaul, MD,DM, FACC
role: PRINCIPAL_INVESTIGATOR
affiliation: CARE Hospitals Hyderabad, India
name: Sreenivas A Kumar, MD, DM, FACC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roncalli J, Mouquet F, Piot C, Trochu JN, Le Corvoisier P, Neuder Y, Le Tourneau T, Agostini D, Gaxotte V, Sportouch C, Galinier M, Crochet D, Teiger E, Richard MJ, Polge AS, Beregi JP, Manrique A, Carrie D, Susen S, Klein B, Parini A, Lamirault G, Croisille P, Rouard H, Bourin P, Nguyen JM, Delasalle B, Vanzetto G, Van Belle E, Lemarchand P. Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial. Eur Heart J. 2011 Jul;32(14):1748-57. doi: 10.1093/eurheartj/ehq455. Epub 2010 Dec 2.
citation: Strauer BE, Yousef M, Schannwell CM. The acute and long-term effects of intracoronary Stem cell Transplantation in 191 patients with chronic heARt failure: the STAR-heart study. Eur J Heart Fail. 2010 Jul;12(7):721-9. doi: 10.1093/eurjhf/hfq095.
citation: Dohmann HF, Silva SA, Sousa AL, Braga AM, Branco RV, Haddad AF, Oliveira MA, Moreira RC, Tuche FA, Peixoto CM, Tura BR, Borojevic R, Ribeiro JP, Nicolau JC, Nobrega AC, Carvalho AC. Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction - MiHeart/AMI study. Trials. 2008 Jul 3;9:41. doi: 10.1186/1745-6215-9-41.