Clinical trial NCT02672163: Autologous Atrial Appendage Derived Cells in the Treatment of Heart Failure
Official title: Epicardial Delivery of Autologous Atrial Appendage Micrografts During Coronary Artery Bypass Surgery - Safety and Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Keywords: autologous micrografts
heart failure
coronary artery bypass surgery
cell therapy
atrial appendage
epicardial cell delivery
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
First posted: 2016-02-03
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety; need for vasoactive medication
timeFrame: 6 months
measure: Safety; cardiac index in l/min/m
timeFrame: 6 months
measure: Safety; hemoglobin in g/l
timeFrame: 6 months
measure: Safety; oxygen saturation in the pulmonary arterial blood (SvO2) in %
timeFrame: 6 months
measure: Safety; serum potassium level in mmol/l
timeFrame: 6 months
measure: Safety; blood glucose level in mmol/l
timeFrame: 6 months
measure: Safety; Left ventricular ejection fraction (EF) in %
timeFrame: 6 months
measure: Safety; pericardial effusion in mm
timeFrame: 6 months
measure: Safety: telemetric monitoring of rhythm
timeFrame: 6 months
measure: Feasibility: Success in completing the delivery of the cell sheet to the myocardium
timeFrame: 6 months
measure: Feasibility: Waiting time in minutes for the cell sheet
timeFrame: 6 months
measure: Feasibility: Waiting time in minutes for the heart
timeFrame: 6 months
measure: Feasibility: Closing the right atrial appendage
timeFrame: 6 months
Secondary outcomes:
measure: Left ventricular wall thickness
timeFrame: 6 months
measure: Change in the amount of myocardial scar tissue
timeFrame: 6 months
measure: Change in left ventricular ejection fraction
timeFrame: 6 months
measure: Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels
timeFrame: 6 months
measure: New York Heart Association class
timeFrame: 6 months
measure: Days in hospital
timeFrame: 1 month
measure: Changes in the quality of life.
timeFrame: 6 months
measure: Change in movement and diastolic function of left ventricular wall
timeFrame: 6 months
measure: Local changes in systolic and diastolic function
timeFrame: 3 months
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Annu Nummi
Study officials:
affiliation: Heart and Lung Center, Helsinki University Hospital
name: Ari Harjula, Prof
role: STUDY_DIRECTOR
References:
citation: Lehtinen M, Patila T, Vento A, Kankuri E, Suojaranta-Ylinen R, Poyhia 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.
citation: Lehtinen M, Schildt J, Ahonen A, Nikkinen P, Lauerma K, Sinisalo J, Kankuri E, Vento A, Patila 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.
citation: Lehtinen M, Patila 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.
citation: 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. doi: 10.2174/1566523216666160104141809.
citation: Nummi A, Mulari S, Stewart JA, Kivisto S, Teittinen K, Nieminen T, Lampinen M, Patila T, Sintonen H, Juvonen T, Kupari M, Suojaranta R, Kankuri E, Harjula A, Vento A; AADC consortium. Epicardial Transplantation of Autologous Cardiac Micrografts During Coronary Artery Bypass Surgery. Front Cardiovasc Med. 2021 Sep 14;8:726889. doi: 10.3389/fcvm.2021.726889. eCollection 2021.
citation: Nummi A, Nieminen T, Patila T, Lampinen M, Lehtinen ML, Kivisto S, Holmstrom M, Wilkman E, Teittinen K, Laine M, Sinisalo J, Kupari M, Kankuri E, Juvonen T, Vento A, Suojaranta R, Harjula A; AADC consortium. Epicardial delivery of autologous atrial appendage micrografts during coronary artery bypass surgery-safety and feasibility study. Pilot Feasibility Stud. 2017 Dec 20;3:74. doi: 10.1186/s40814-017-0217-9. eCollection 2017.