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Published on: January 21, 2018
Transendocardial injection of expanded autologous CD34+ cells after myocardial infarction: Design of the EXCELLENT
Jerome Roncalli1, François Roubille2, Nicolas Meyer3
1Department of Cardiology, Institute Cardiomet, Centre d'Investigations Cliniques Biotherapies 1436, INSERM I2MC 1297, Toulouse University Hospital, Toulouse, France.
Insights
This study investigates autologous CD34+ cell therapy for acute myocardial infarction (AMI). It evaluates the safety and potential efficacy of transendocardial cell delivery in patients with reduced left ventricular ejection fraction, aiming to improve cardiac repair.
Area of Science:
- Cardiology
- Regenerative Medicine
- Cell Therapy
Background:
- Acute myocardial infarction (AMI) leads to cardiomyocyte necrosis, impacting left ventricular (LV) function and patient outcomes.
- CD34+ cell therapy shows promise for myocardial repair and improving outcomes post-AMI.
- Optimizing CD34+ cell dose and administration route is crucial for clinical effectiveness.
Purpose of the Study:
- To evaluate the safety and potential efficacy of transendocardial expanded CD34+ cell administration in patients with AMI and reduced LV ejection fraction.
- To assess the feasibility of an automated manufacturing platform for autologous CD34+ cell expansion and delivery.
- To determine the impact of CD34+ cell therapy on major adverse cardiac events and LV remodeling.
Main Methods:
- A multicentre, open-label, randomized controlled phase I/IIb trial design.
- Patients with large AMI and LV ejection fraction <50% randomized 3:1 to cell therapy plus standard care or standard care alone.
- Autologous CD34+ cells expanded for 9 days using an automated platform and administered via transendocardial injection.
Main Results:
- The primary endpoint is the incidence of major adverse cardiac events over 6 months.
- Secondary endpoints include changes in LV end-systolic volume index and infarct viability.
- This trial is the first to assess automated CD34+ cell expansion and transendocardial delivery in AMI patients.
Conclusions:
- Autologous CD34+ cell therapy for AMI faces current technological limitations.
- This study provides initial data on the feasibility and potential effects of this novel therapeutic approach.
- Further research is needed to overcome constraints and optimize CD34+ cell therapy for myocardial regeneration.
Aims:
The extent of irreversible cardiomyocyte necrosis after acute myocardial infarction (AMI) is a major determinant of residual left ventricular (LV) function and clinical outcome. Cell therapy based on CD34+ cells has emerged as an option to help repair the myocardium and to improve outcomes. The dose of CD34+ cells and the route of administration are two important factors that will determine the clinical effectiveness of the approach, provided it is robust and feasible. Here, we describe the rationale and design of the multicentre open-label randomized controlled phase I/IIb trial evaluating the safety and the likelihood of efficacy of transendocardial expanded CD34+ cell administration in patients presenting with AMI and a reduced LV ejection fraction.
Methods:
Patients with a large AMI and LV ejection fraction <50% are randomized 3:1 to transendocardial expanded CD34+ cell injection plus standard of care or standard of care alone. Patients randomized to intervention are treated with lenograstim for 5 days before 220 ± 10 mL blood cell harvest from which autologous CD34+ cells are purified and expanded for 9 days using an automated good manufacturing practice compliant platform. The primary endpoint is the incidence of major adverse cardiac events over 6 months. The main secondary endpoints are LV end systolic volume index and the viability of the infarcted segments.
Conclusions:
Autologous CD34+ cell therapy is currently limited by technological constraints. This is the first trial to evaluate the feasibility and potential effect of CD34+ cells after automated expansion and transendocardial administration in patients with large AMI.
