Prospective, Controlled and Randomized Clinical Trial on Cardiac Cell Regeneration With Laser and Autologous Bone Marrow Stem Cells, in Patients With Coronary Disease and Refractory Angina

Study Overview
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Brief Summary
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Coronary disease is one of the most frequent pathology of the modern world and the leading cause of death in the investigators country. In Spain more than 50.000 coronary percutaneous intervention and more than 5.000 coronary artery bypass graft (CABG) procedures are performed every year. Despite this data about 12% of patients have diffuse coronary disease and are not candidates to conventional therapies. Also between 15-25% of patients undergoing coronary bypass grafting receive an incomplete revascularization due to the poor quality of the coronary vessels. Transmyocardial revascularization (TMR) is a surgical procedure that uses a laser to create channels through the myocardial, so this laser stimulates local angiogenesis and provides blood in the ischemic area. Results of this procedure have shown clear benefits in terms of reduction of angina and increase of survival of patients, compared to medical treatment. Cell therapy in heart disease is offering in recent years encouraging results despite the methodological difficulties that being able to use this technique sometimes involves. The basis lies in the potential ability of stem cells to differentiate into any type of adult cell. In the case of cardiac cell therapy, stem cells can differentiate into myocardial cells or vascular cells capable of developing angiogenesis. Further studies are needed to draw firm conclusions about the clinical impact that the use of stem cells has on cardiovascular disease. Recently a system has been developed to create, at the same time and in a simple and effective way, the laser channels and the introduction of stem cells on the edges of these channels. This system called PHOENIX ™ consists of a laser probe capable of creating transmural channels in the myocardium. Based on the what has just been explained, it is quite possible that the combination of both therapies can increase successful results regarding the reduction in angina these patients need. Initially, and after having some experience with this type of treatment, the results could be analyzed and compared with the results obtained through laser therapy, with the help of a controlled clinical trial, such as the one the investigators are proposing.

Official Title
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Prospective, Controlled and Randomized Clinical Trial on Cardiac Cell Regeneration With Laser and Autologous Bone Marrow Stem Cells, in Patients With Coronary Disease and Refractory Angina

Conditions
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Angina, Coronary Disease

Intervention / Treatment
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* Procedure: Transmyocardial revascularization (TMR) with Holmium YAG laser
* Procedure: Transmyocardial revascularization (TMR) with Holmium YAG laser plus the patient's own stem cells extracted from bone marrow.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18 years of age. Patients with at least one area of myocardial ischemia or chronic myocardial infarction of the left ventricle demonstrated by any imaging technique not amenable to conventional revascularization and angina refractory to medical treatment. Ejection fraction> 25% measured in the six months prior to the procedure. Participants must be mentally competent to give consent for inclusion in the clinical trial Exclusion Criteria: Patients with unstable angina defined as the need for intravenous nitrates at the time of surgery. Recent myocardial infarction (within 15 days before the procedure). Patients with decompensated heart failure at the time of surgery. Severe or life threatening arrhythmia (ventricular tachycardia or fibrillation) in the week before the procedure. Patients requiring some type of concomitant valvular surgery. Patients with severe obstructive lung disease criteria who are considered as not capable of bearing general anesthesia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment Control<br>Transmyocardial revascularization (TMR) with Holmium YAG (yttrium aluminium garnet) laser, according to habitual clinical practice in the Department of Cardiovascular Surgery. | Procedure: Transmyocardial revascularization (TMR) with Holmium YAG laser<br>* Transmyocardial revascularization (TMR) is a surgical procedure that uses a laser to create channels through the myocardial, so this laser stimulates local angiogenesis and provides blood in the ischemic area.<br>|
| Experimental: Experimental Treatment<br>Transmyocardial revascularization (TMR) with Holmium YAG laser plus the patient's own stem cells extracted from bone marrow. | Procedure: Transmyocardial revascularization (TMR) with Holmium YAG laser plus the patient's own stem cells extracted from bone marrow.<br>* The system called PHOENIXTM consists of a laser probe with Holmium:YAG energy capable of creating transmural channels in the myocardium. Surrounding this fibre 3 needles with side holes are arranged so that the implantation of stem cells is done on the edges of the channel and not on the channel itself. This device is capable of distributing stem cells in those channels created by the laser, carrying out both procedures simultaneously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New York Heart Association (NYHA)classification for angina | The main variable under study is the percentage of patients achieving a decrease in two levels of the NYHA classification for angina. | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The demographic, intra and postoperative variables | The demographic variables and patients' cardiovascular history will be collected. All the intra and postoperative variables will be collected, as well as the data obtained by cytometry (amount of cells injected into each appropriate patient) | one year | 
| Tests | Before surgery and 12 months after it a test of ischemia provocation through isotopes will be carried out in order to measure the percentage of ischemic area (SPECT or Single Photon Emission Computed Tomography) and maximum effort capacity before the occurrence of the angina. The ejection fraction, the end-systolic volume and the end-diastolic volume of the left ventricle will be examined through an echocardiogram and a pre- and postoperative cardiac magnetic resonance imaging study. | one year | 
| Quality of Life | The EQ-5D questionnaire (standardised instrument for use as a measure of health outcome)will be completed for the subjective assessment of the quality of life that the patient perceives to have. | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Refractory angina, Transmyocardial revascularization, Stem cells, Diffuse coronary disease not amenable to percutaneous coronary intervention, and angina, despite proper medical treatment