None listed
Conditions
Brief summary
The aim of this study is to evaluate the efficacy and safety of percutaneous catheter-based direct intramyocardial injection of autologous bone marrow cells, a new therapeutic strategy, in patients with severe CAD experiencing symptoms of angina and chronic ischaemic heart failure, where all conventional medical treatment options have been exhausted. Our recent randomised, placebo controlled trial (Angiogenesis - Protect CAD) demonstrated the beneficial effects of bone marrow cell therapy over placebo saline injection on symptoms, functional capacity and LVEF in patients with chronic myocardial ischaemia who failed conventional medical treatment and revascularisation procedures. However, the clinical implications of this treatment for severe CAD needs to be demonstrated in a larger population with more definitive primary endpoints. Positive evidence to support the use of this therapeutic approach may have a profound impact on the health and well being of chronically ill CAD patients, by providing a catheter-based treatment that is cost-effective and utilises easily reproducible techniques for the harvesting and injection of bone marrow. Furthermore, the patients's own bone marrow may be considered as a readily available resource which overcomes issues associated with immunological rejection response.
Interventions
Device - Myostar injection catheter.
On the day of the endomyocardial injection procedure, bone marrow cells will be obtained from the iliac crest under local anaesthesia in a sterile environment. A total of 80 ml of marrow blood will be aspirated, placed in heparinised phosphate buffered saline, and transported immediately to a culture laboratory dedicated to cell manipulation for bone marrow transplantation. Mononuclear cells will be isolated by Ficoll density gradient centrifugation, washed
Device - Myostar injection catheter. On the day of the endomyocardial injection procedure, bone marrow cells will be obtained from the iliac crest under local anaesthesia in a sterile environment. A total of 80 ml of marrow blood will be aspirated, placed in heparinised phosphate buffered saline, and transported immediately to a culture laboratory dedicated to cell manipulation for bone marrow transplantation. Mononuclear cells will be isolated by Ficoll density gradient centrifugation, washed twice in phosphate buffered saline, re-suspended in phosphate buffered saline enriched with 10% autologous plasma at a concentration of 10 to the 7th power cells per ml, and returned directly to Cardiac Catheterisation Laboratory (CCL) for use. The composition of the final cell suspension will be determined by flow cytometry. Standard bone marrow examinations (smear and trephine biopsy) will be performed, as well as microbiological examination and culture, to exclude any abnormalities. Following bone marrow aspiration, participants will be transported to the CCL where an initial diagnostic left ventriculography and coronary angiography will be performed to visualise the target region for implantation procedure and the corresponding coronary anatomy. An electromechanical mapping system (NOGA XP, Biosense) will be employed to identify the target ischaemic area/s for injection and to pinpoint any scarred or infarcted areas of myocardium. The system uses a location pad with coils generating ultralow magnetic field energy, a stationary reference catheter with a miniature magnetic field sensor located on the body surface, a navigation sensor mapping catheter and electrodes providing endocardial signals, and a workstation for information processing and 3-dimensional left ventricular reconstruction. Once the mapping procedure is complete, percutaneous myocardial injection of autologous bone marrow cells (10 to 12 injections of 0.1 ml of bone marrow of concentration of 10 7th power cells per mL at each pre-determined target site) will occur on the same day in the CCL. Once all results of the six month follow-up investigations is known, the treatment arm allocation of participants will be "unblinded". Participants in the control group will be given the option to crossover to the treatment group, that is, to receive autologous bone marrow endomyocardial injection.
Sponsors
John Hunter Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Age 18 -80 years. CCS classification II-IV angina and/or NYHA classification II-III heart failure symptoms. Received stable and “best” cardiac medical therapy including diuretics, long-acting nitrates, beta-blocker, and angiotensin-converting enzyme inhibitors without control of symptoms. Not suitable for conventional revascularization (due to diffuse disease, chronic total occlusion, lack of graftable vessels or any combination thereof). LVEF <40% by echocardiography. Recent coronary angiogram (within the last 6 months) to document the coronary anatomy and insure the presence of Coronary Artery Disease (CAD) that is not amenable to standard revascularization procedures. Serum creatinine less than 250mmol/L, normal liver function, and normal blood count: white blood cell (WBC) count, granulocytes; platelet count, haemolglobin (Hb). Reversible perfusion defect on SPECT. Hemodynamically stable. Subject is willing to comply with specified follow-up evaluations.
Exclusion criteria
Atrial fibrillation. History of syncope or major ventricular arrhythmias such as sustained ventricular tachycardia or ventricular fibrillation. Severe valve disease. Aortic or mitral valve prosthesis. History of cancer in last 5 years. Acute or chronic active sepsis, including human immunodeficiency virus (HIV) positive; hepatitis B or C positive. Left ventricular (LV) wall thickness less than 8 mm in the target territory (by echocardiography or MRI). LV thrombus and/or spontaneous echo-contrast in the LV detected by echocardiography or LV aneurysm. Severe aorto-femoral-iliac disease. Recent heart attack within the last 30 days. Hypertrophic or restrictive cardiomyopathy. Severe co-morbidity associated with a reduction in life expectancy of less than 1 year.
Outcome results
None listed