Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial design

Abstract

Aims: Cardiopoiesis is a conditioning programme that aims to upgrade the cardioregenerative aptitude of patient-derived stem cells through lineage specification. Cardiopoietic stem cells tested initially for feasibility and safety exhibited signs of clinical benefit in patients with ischaemic heart failure (HF) warranting definitive evaluation. Accordingly, CHART-1 is designed as a large randomized, sham-controlled multicentre study aimed to validate cardiopoietic stem cell therapy.

Methods: Patients (n = 240) with chronic HF secondary to ischaemic heart disease, reduced LVEF (<35%), and at high risk for recurrent HF-related events, despite optimal medical therapy, will be randomized 1:1 to receive 600 × 10(6) bone marrow-derived and lineage-directed autologous cardiopoietic stem cells administered via a retention-enhanced intramyocardial injection catheter or a sham procedure. The primary efficacy endpoint is a hierarchical composite of mortality, worsening HF, Minnesota Living with Heart Failure Questionnaire score, 6 min walk test, LV end-systolic volume, and LVEF at 9 months. The secondary efficacy endpoint is the time to cardiovascular death or worsening HF at 12 months. Safety endpoints include mortality, readmissions, aborted sudden deaths, and serious adverse events at 12 and 24 months.

Conclusion: The CHART-1 clinical trial is powered to examine the therapeutic impact of lineage-directed stem cells as a strategy to achieve cardiac regeneration in HF populations. On completion, CHART-1 will offer a definitive evaluation of the efficacy and safety of cardiopoietic stem cells in the treatment of chronic ischaemic HF.

Trial registration: NCT01768702.

Keywords: Cardiopoiesis; Heart failure; Ischaemic cardiomyopathy; Regenerative medicine; Stem cell.

Figure 1

Study flow chart. MSC, mesenchymal stem cells.

Figure 2

Cardiopoietic stem cell procurement and processing prior to the delivery procedure. Following bone marrow harvest, mesenchymal stem cells (MSCs) are purified and expanded. Following standard operating procedures, cardiopoiesis is imposed for lineage guidance of MSCs to derive cardiopoietic stem cells. Stem cells meeting pre‐defined release criteria are delivered in an autologous fashion to patients with ischaemic cardiomyopathy using a catheter‐based endomyocardial delivery procedure.

Figure 3

Catheter‐based delivery system. Endomyocardial delivery catheter designed for enhanced endomyocardial retention of stem cells (C‐Cathez®) features a thumbwheel control for distal catheter tip deflection (upper left panel), a curved needle design with side holes (inset), and a luer lock connector for study injection with adjustable needle advancing mechanism (lower left).