Allogeneic Stem Cells Implantation Combined With Coronary Bypass Grafting in Patients With Ischemic Cardiomyopathy

• ClinicalTrials.gov Identifier: NCT01753440
• Recruitment Status: Completed
• First Posted: December 20, 2012
• Last Update Posted: May 7, 2019
• Sponsor: AHEPA University Hospital
• Information provided by (Responsible Party): Kyriakos Anastasiadis, AHEPA University Hospital

Tracking Information

• First Submitted Date: December 18, 2012
• First Posted Date: December 20, 2012
• Last Update Posted Date: May 7, 2019
• Actual Study Start Date: November 2012
• Actual Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 3, 2019)

• iMP-related adverse events [ Time Frame: 12 months ]
  Major adverse cardiac and cerebrovascular events including death, postoperative myocardial infarction, need for revascularization, stroke, hospitalization for worsening heart failure, myocardial rupture, infectious myocarditis, or sustained ventricular arrhythmias.
• Hypersensitivity [ Time Frame: 12 months ]
  Hypersensitivity reaction (fever, urticaria, hemolytic anemia, hypotension, immune thrombocytopenia)

Original Primary Outcome Measures (submitted: December 19, 2012)

• Left ventricular ejection fraction [ Time Frame: one year ]
  Change in left ventricular ejection fraction assesed with echocardiography after intramyocardial implantation of allogeneic mesenchymal stem cells.
• Myocardial segmental perfusion [ Time Frame: one year ]
  change in segmental perfusion as assesed with SPECT after intramyocardial implantation of allogeneic mesenchymal stem cells.

Current Secondary Outcome Measures (submitted: May 3, 2019)

• Scar reduction [ Time Frame: 4 months ]
  Myocardial scar size reduction assessed with SPECT
• Scar reduction [ Time Frame: 12 months ]
  Myocardial scar size reduction assess with SPECT
• LVEF [ Time Frame: 12 months ]
  Left ventricular ejection fraction
• Change in quality of life [ Time Frame: 12 months ]
  Quality of life evaluated with MLHFQ

Original Secondary Outcome Measures (submitted: December 19, 2012)

• all-cause mortality [ Time Frame: one year ]
• all-cause morbidity [ Time Frame: one year ]
• major adverse cardiac and cerebrovascular events [ Time Frame: one year ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Allogeneic Stem Cells Implantation Combined With Coronary Bypass Grafting in Patients With Ischemic Cardiomyopathy
• Official Title: Study on the Safety and Efficacy of Allogeneic Mesenchymal Stem Cell Implantation Combined With Bypass Grafting in Patients With Coronary Artery Disease and Ischemic Cardiomyopathy.
• Brief Summary: The aim of the present study is to investigate safety and efficacy of intramyocardial implantation of a novel mesenchymal precursor cell type (iMP) in patients with ischemic cardiomyopathy at the time of coronary artery bypass grafting.
• Detailed Description: This study aims to investigates in situ cardiac regeneration utilizing precision delivery of a novel mesenchymal precursor cell type (iMP) during coronary artery bypass surgery (CABG) in patients with ischemic cardiomyopathy (LVEF < 40 %). Preoperative scintigraphy imaging (SPECT) will be used to identify hibernating myocardium not suitable for conventional myocardial revascularization for iMP implantation. iMP cells will be implanted intramyocardially in predefined viable peri-infarct areas that show poor perfusion, which could not be grafted due to poor target vessel quality. Postoperatively, SPECT will be used to identify changes in scar area.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Coronary Artery Disease
• Ischemic Cardiomyopathy

Intervention

Procedure: Intramyocardial implantation of of a novel mesenchymal precursor cell type (iMP).

Intramyocardial implantation of a novel mesenchymal precursor cell type (iMP).

Study Arms

Stem cells implantation

Patients with severe coronary artery disease and chronic ischemic cardiomyopathy with a LVEF ≤40% who are scheduled for elective CABG according to accepted guidelines. Additional criteria include the following: age <75 years, history of myocardial infarction (not less than 14 days before the procedure), LVEF ≤40 % assessed with echocardiography, and a distinct area of dyskinetic or akinetic left ventricular myocardium corresponding with the infarct localization.

Intervention: Procedure: Intramyocardial implantation of of a novel mesenchymal precursor cell type (iMP).

Publications *

• Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, Tracy M, Ghersin E, Johnston PV, Brinker JA, Breton E, Davis-Sproul J, Schulman IH, Byrnes J, Mendizabal AM, Lowery MH, Rouy D, Altman P, Wong Po Foo C, Ruiz P, Amador A, Da Silva J, McNiece IK, Heldman AW, George R, Lardo A. Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA. 2012 Dec 12;308(22):2369-79. Erratum in: JAMA. 2013 Aug 21;310(7):750. George, Richard [added]; Lardo, Albert [added].
• Anastasiadis K, Antonitsis P, Doumas A, Koliakos G, Argiriadou H, Vaitsopoulou C, Tossios P, Papakonstantinou C, Westaby S. Stem cells transplantation combined with long-term mechanical circulatory support enhances myocardial viability in end-stage ischemic cardiomyopathy. Int J Cardiol. 2012 Mar 22;155(3):e51-3. doi: 10.1016/j.ijcard.2011.07.062. Epub 2011 Aug 17.
• Menasche P. Cardiac cell therapy: lessons from clinical trials. J Mol Cell Cardiol. 2011 Feb;50(2):258-65. doi: 10.1016/j.yjmcc.2010.06.010. Epub 2010 Jun 30. Review.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 3, 2019): 11
• Original Estimated Enrollment (submitted: December 19, 2012): 30
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age from 18 to 75 years
• Severe coronary artery disease amenable to surgical revascularization according to current guidelines
• History of acute myocardial infarction at least 14 days previously
• Left ventricular ejection fraction (LVEF) ≤ 40% as assessed with echocardiography
• Distinct area of dyskinetic or akinetic left ventricular myocardium corresponding with the infarct localization
• Patient's informed consent obtained

Exclusion Criteria:

• Emergency operation
• Debilitating chronic disease (eg. malignancy or terminal renal failure)
• Concomitant valve surgery
• Previous cardiac surgery
• Malignant ventricular arrhythmias
• Haematologic disease
• Woman in reproductive age
• Severe psychiatric illness

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Greece

Administrative Information

• NCT Number: NCT01753440
• Other Study ID Numbers: AHEPA_CTL_01
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Kyriakos Anastasiadis, AHEPA University Hospital
• Study Sponsor: AHEPA University Hospital
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kyriakos Anastasiadis, MD, PhD FETCS; AHEPA University Hospital

• PRS Account: AHEPA University Hospital
• Verification Date: May 2019