Autologous Atrial Appendage Derived Cells in the Treatment of Heart Failure

NCT02672163 | Completed DMC

• 1 other identifier: 180/13/03/02/2013
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure

Keywords

autologous micrografts; heart failure; coronary artery bypass surgery; cell therapy; atrial appendage; epicardial cell delivery

Outcome Measures

Primary Outcomes (13)

• Safety; need for vasoactive medication

  For assessing haemodynamics during the operation and at the intensive care unit

  6 months

• Safety; cardiac index in l/min/m

  For assessing haemodynamics during the operation and at the intensive care unit

  6 months

• Safety; hemoglobin in g/l

  For assessing haemodynamics during the operation and at the intensive care unit

  6 months

• Safety; oxygen saturation in the pulmonary arterial blood (SvO2) in %

  For assessing haemodynamics during the operation and at the intensive care unit

  6 months

• Safety; serum potassium level in mmol/l

  For assessing haemodynamics during the operation and at the intensive care unit

  6 months

• Safety; blood glucose level in mmol/l

  For assessing haemodynamics during the operation and at the intensive care unit

  6 months

• Safety; Left ventricular ejection fraction (EF) in %

  For assessing cardiac function during and after the operation by echocardiogram

  6 months

• Safety; pericardial effusion in mm

  For assessing cardiac function after the operation by echocardiogram

  6 months

• Safety: telemetric monitoring of rhythm

  For assessing cardiac function after the operation

  6 months

• Feasibility: Success in completing the delivery of the cell sheet to the myocardium

  Measured in 0= success, 1= no success

  6 months

• 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

• 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

• 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 Outcomes (9)

• Left ventricular wall thickness

  6 months

• Change in the amount of myocardial scar tissue

  6 months

• Change in left ventricular ejection fraction

  6 months

• Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels

  6 months

• New York Heart Association class

  6 months

Study Arms (2)

AACD-Therapy group

EXPERIMENTAL

6 patients are recruited to the AADC-therapy group. Autologous atrial appendage derived cells (AADCs) are harvested from the appendage tissue removed during the venal cannulation of bypass. The cells and their extracellular matrix are placed with tissue clue to Cormatrix-sheet and further on top of the myocardium in the area of infarction scar. The procedure is done simultaneously with CABG surgery. The patients will be carefully monitored after the operations and cardiac MRI and echocardiogram will be performed previously to surgery as well as during the follow ups.

Procedure: CABG surgery; Procedure: AADC therapy

Control group

ACTIVE COMPARATOR

20 patients are recruited to form the control group. They are patients scheduled for elective CABG surgery and they meet the same inclusion and exclusion criteria as the therapy group. There patients are followed as the hospital protocol with out any additional imagination or blood tests.

Procedure: CABG surgery

Interventions

CABG surgery PROCEDURE

Elective CABG surgery

AACD-Therapy group; Control group

AADC therapy PROCEDURE

Atrial appendage derived cells are placed on the site of a infarct scar with matrix sheet

AACD-Therapy group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent obtained
• Left ventricular ejection fraction (LVEF) between ≤50% and ≥15%
• New York Heart Association (NYHA) Class II-IV heart failure symptoms

You may not qualify if:

• 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

Sponsors & Collaborators

• Helsinki University Central Hospital: lead

Study Sites (1)

Annu Nummi

Helsinki, 00029, Finland

Location

Related Publications (6)

• 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.

  PMID: 25142068 BACKGROUND

• 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.

  PMID: 25762563 BACKGROUND

• 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.

  PMID: 25797522 BACKGROUND

• 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.

  PMID: 26725880 BACKGROUND

• 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.

  PMID: 34595223 DERIVED

• 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.

  PMID: 29276625 DERIVED

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Ari Harjula, Prof

  Heart and Lung Center, Helsinki University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Clinical research

Study Record Dates

• First Submitted: December 28, 2015
• First Posted: February 3, 2016
• Study Start: February 1, 2016
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: March 5, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)