Cell Repair in Heart Failure

• Safety: up to one year
  
• Efficacy
  
• Co-primary endpoints at 180 Days
  
• Perfusion (MIBI SPECT)
  
• Function (CMR)
  

• Efficacy: at 180 days
  
• Perfusion (CMR)
  
• Function (ECHO, SPECT)
  
• Exercise (VO2 Max)
  
• QOL
  

Study Objectives:

1. Evaluate the safety of a single administration of bone marrow mononuclear cells by retrograde coronary venous delivery.
2. Evaluate the bioactivity of bone marrow mononuclear cells in mediating increased perfusion in viable underperfused areas of myocardium.
3. Evaluate the ability of bone marrow mononuclear cells to improve myocardial function specifically regional wall motion and cardiac synchronisation.
4. Evaluate the use of potential bioactivity assays and clinical outcomes for assessing bone marrow mononuclear cell- induced myocardial changes.

Study Design:

A phase I/II, randomised, double-blind, placebo controlled, single-centre study of bone marrow mononuclear cells by percutaneous retrograde coronary venous delivery to patients with ischaemic heart failure and no standard revascularisation options.

Study Population:

Patients with symptomatic ischaemic heart failure, not amenable to conventional revascularisation strategies (PCI, CABG, LVAD) or transplantation.

Independent Eligibility:

The results of the screening procedures will be compiled and submitted to an independent interventional cardiologist and cardiac surgeon who are not associated with the study for consideration for enrolment. It will be the independent reviewer’s responsibility to confirm eligibility prior to a patient participating in the study.

Product:

Autologous bone marrow mononuclear, the first 6 safety and feasibility patients (open-labelled) will receive a sub-population of Indium-111 labelled cells to assess feasibility of delivery. The remaining patients will either receive Active: Bone marrow mononuclear cells and 5 % HSA Placebo: 5% HSA

Route:

Retrograde coronary venous delivery The total dose of bone marrow mononuclear cells or placebo will be divided into two, each administered as a 10ml bolus into a selective coronary veins. There will be significant patient heterogeneity regarding size of ischaemic viable territory present and anatomy of venous system. We aim to treat two veins, individual SPECT and venogram results will be used to direct the venous anatomy to be targeted. An attempt will be made to cover as large an area as possible of a patient’s ischaemic viable territory. The total dose of cells will remain constant between patients.

Safety:

The first 6 patients will receive cells as an adjunct to Cardiac resynchronization Therapy and ICD. An external Data Safety and Monitoring Board has also been appointed to oversee this study.