Autologous Atrial Appendage Derived Cells in the Treatment of Heart Failure

Heart Failure Clinical Trial

Official title:

Epicardial Delivery of Autologous Atrial Appendage Micrografts During Coronary Artery Bypass Surgery - Safety and Feasibility Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02672163
• Other study ID #: 180/13/03/02/2013
• Status: Completed
• Phase: N/A
• Start date: February 2016
• Est. completion date: December 2019

Study information

• Verified date: March 2020
• Source: Helsinki University Central Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate the safety and clinical feasibility of epicardially delivered autologous atrial appendage micrografts in the treatment of heart failure. The micrografts consisting atrial-derived cells and their extracellular matrix, are placed on an infarction scar during CABG surgery.

Description:

The atrial appendages are a tissue reservoir for cardiomyocyte stem and precursor cells. During coronary artery bypass graft (CABG) surgery part of the right atrial appendage can be excised upon insertion of the right atrial cannula of the heart-lung machine. This study aims to address the surgical feasibility and patient safety of epicardially delivered atrial appendage micrografts during CABG surgery.

Autologous cardiac cells are harvested from right atrial appendage during CABG of six patients. Micrografts consisting atrial appendage-derived cells (AADCs) and their extracellular matrix (ECM) of the atrial appendage are mechanically processed. The cells are placed on a tissue-engineered sheet with fibrin gel and tissue clue and further delivered epicardially on top of a infarction scar. Parameters including echocardiography reflecting cardiac insufficiency are studied pre- and post-operatively as well as at three and six months of the follow-up. Cardiac functional magnetic resonance imaging is performed preoperatively and at six-months follow-up. 20 patients will be recruited to serve as a control group. They are scheduled for elective CABG and are treated according to the normal hospital protocol, without the ECM sheet.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Informed consent obtained

• Left ventricular ejection fraction (LVEF) between =50% and =15%

• New York Heart Association (NYHA) Class II-IV heart failure symptoms

Exclusion Criteria:

• Heart failure due to left ventricular outflow tract obstruction

• History of life-threatening and possibly repeating ventricular arrhythmias or resuscitation, or an implantable cardioverter-defibrillator

• Stroke or other disabling condition within 3 months before screening

• Severe valve disease or scheduled valve surgery

• Renal dysfunction (GFR <84 ml/min/1.73m)

• Other disease limiting life expectancy

• Contraindications for coronary angiogram or MRI

• Participation in some other clinical trial

Related Conditions & MeSH terms

• Heart Failure

Intervention

Procedure:
• CABG surgery
Elective CABG surgery
• AADC therapy
Atrial appendage derived cells are placed on the site of a infarct scar with matrix sheet

Locations

Country	Name	City	State
Finland	Annu Nummi	Helsinki

Sponsors (1)

Lead Sponsor	Collaborator
Helsinki University Central Hospital

Country where clinical trial is conducted

Finland, 

References & Publications (4)

Lampinen M, Vento A, Laurikka J, Nystedt J, Mervaala E, Harjula A, Kankuri E. Rational Autologous Cell Sources For Therapy of Heart Failure - Vehicles and Targets For Gene and RNA Therapies. Curr Gene Ther. 2016;16(1):21-33. Review. — View Citation

Lehtinen M, Pätilä T, Kankuri E, Lauerma K, Sinisalo J, Laine M, Kupari M, Vento A, Harjula A; Helsinki BMMC Collaboration. Intramyocardial bone marrow mononuclear cell transplantation in ischemic heart failure: Long-term follow-up. J Heart Lung Transplant. 2015 Jul;34(7):899-905. doi: 10.1016/j.healun.2015.01.989. Epub 2015 Feb 7. — View Citation

Lehtinen M, Pätilä T, Vento A, Kankuri E, Suojaranta-Ylinen R, Pöyhiä R, Harjula A; Helsinki BMMC Collaboration. Prospective, randomized, double-blinded trial of bone marrow cell transplantation combined with coronary surgery - perioperative safety study. Interact Cardiovasc Thorac Surg. 2014 Dec;19(6):990-6. doi: 10.1093/icvts/ivu265. Epub 2014 Aug 20. — View Citation

Lehtinen M, Schildt J, Ahonen A, Nikkinen P, Lauerma K, Sinisalo J, Kankuri E, Vento A, Pätilä T, Harjula A; Helsinki BMMC Collaboration. Combining FDG-PET and 99mTc-SPECT to predict functional outcome after coronary artery bypass surgery. Eur Heart J Cardiovasc Imaging. 2015 Sep;16(9):1023-30. doi: 10.1093/ehjci/jev032. Epub 2015 Mar 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety; need for vasoactive medication	For assessing haemodynamics during the operation and at the intensive care unit	6 months
Primary	Safety; cardiac index in l/min/m	For assessing haemodynamics during the operation and at the intensive care unit	6 months
Primary	Safety; hemoglobin in g/l	For assessing haemodynamics during the operation and at the intensive care unit	6 months
Primary	Safety; oxygen saturation in the pulmonary arterial blood (SvO2) in %	For assessing haemodynamics during the operation and at the intensive care unit	6 months
Primary	Safety; serum potassium level in mmol/l	For assessing haemodynamics during the operation and at the intensive care unit	6 months
Primary	Safety; blood glucose level in mmol/l	For assessing haemodynamics during the operation and at the intensive care unit	6 months
Primary	Safety; Left ventricular ejection fraction (EF) in %	For assessing cardiac function during and after the operation by echocardiogram	6 months
Primary	Safety; pericardial effusion in mm	For assessing cardiac function after the operation by echocardiogram	6 months
Primary	Safety: telemetric monitoring of rhythm	For assessing cardiac function after the operation	6 months
Primary	Feasibility: Success in completing the delivery of the cell sheet to the myocardium	Measured in 0= success, 1= no success	6 months
Primary	Feasibility: Waiting time in minutes for the cell sheet	Waiting time in minutes for the finished cell sheet to be placed on the myocardium after doing all the required anastomoses	6 months
Primary	Feasibility: Waiting time in minutes for the heart	Waiting time in minutes for the the heart after doing all the anastomoses and before the cell sheet is finished	6 months
Primary	Feasibility: Closing the right atrial appendage	Closing the right atrial appendage after removing the standardized tissue piece for preparing the cell sheet. According to the hospital protocol, appendage is closed with purse string suture. 0 = no additional suturing needed, 1 = additional suturing needed.	6 months
Secondary	Left ventricular wall thickness	Measured by MRI	6 months
Secondary	Change in the amount of myocardial scar tissue	Measured by MRI	6 months
Secondary	Change in left ventricular ejection fraction	Measured by MRI	6 months
Secondary	Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels		6 months
Secondary	New York Heart Association class		6 months
Secondary	Days in hospital		1 month
Secondary	Changes in the quality of life.	measured by questionnaire	6 months
Secondary	Change in movement and diastolic function of left ventricular wall	Measured by MRI	6 months
Secondary	Local changes in systolic and diastolic function	Measured by echocardiogram	3 months