Coronary Artery Disease, Ischemic Heart Disease, Myocardial Ischemia
Conditions
Keywords
STROMAL CELLS, ADIPOSE STROMAL CELLS, REVASCULARIZATION, MYOCARDIUM REVASCULARIZATION, CARDIAC SURGERY, CORONARY ARTERY DISEASE
Brief summary
Treatment of ischemic myocardium has been the subject of intense research in recent years and stem cell therapy is one of the great promises. The InCor laboratory has studied cells from different backgrounds as candidates for cell therapy in the context of myocardial infarction. Evidence in preclinical studies of the application of stromal (mesenchymal) adipose tissue (hASC) in the ischemic heart by both the InCor group (in the animal model in rodents and pigs) and others in the literature suggest relevant benefits on the decrease of deterioration post-infarction. More recently it has been demonstrated that it arises mainly from the formation of new vessels due to paracrine factors, which are secreted by the injected cells. There are currently no studies in Brazil in which the safety of injecting different doses of hASC cells into the heart has been particularly evaluated. Recently, two studies have demonstrated the clinical applicability of hASC in patients with peripheral ischemic disease and stroke. Thus, the objective of this work will be to test the hypothesis that the implantation of autologous stromal cells derived from adipose tissue combined with myocardial revascularization surgery in patients with coronary artery disease
Detailed description
To test the hypothesis that the implantation of adipose-derived autologous cells derived from adipose tissue (hASCs) combined with coronary artery bypass grafting in patients with coronary artery disease is safe and well tolerated, besides being able to promote regional perfusion increase in the injected segments.
Interventions
BIOLOGICALStromal Cells Injection
Adipose stromal cell
Sponsors
Hospital do Coracao
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
DOUBLE BLIND
Intervention model description
It is a randomized, prospective, double-blind, placebo-controlled clinical study. Eligible patients will be randomly divided into 4 groups (one control group and 3 active treatment groups): 10 PATIENTS EACH ARM Control Group - saline injection Low dose group (BD) - hASC injection (1x106 / kg body weight) Intermediate dose group (DI) - injection of hASC (2x106 / kg body weight) High dose group (AD) - hASC injection (4x106 / kg body weight)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* signing the Informed Consent Form (TCLE) * the patient must be a patient with obstructive atherosclerotic coronary artery disease * sex: both men and women are eligible- * Age: between 18 and 80 years of age * the patient should present clinical evidence (angina pectoris or angina equivalent) OR imaging (stress echocardiography, myocardial perfusion scintigraphy, cardiac magnetic resonance imaging) of myocardial ischemia, invasively stratified with coronary angiography * the presence of myocardial ischemia should be confirmed by at least 2 (two) distinct diagnostic methods performed within one year of the patient's inclusion in the study * the patient is a candidate for myocardial revascularization surgery but coronary obstructive lesions, in their entirety, are NOT amenable for surgical treatment in the opinion of the surgeon (main surgeon), depending on the anatomical type, extent or distal involvement of the lesions OR, even if they can be treated surgically as a whole, an unsatisfactory surgical outcome is anticipated in terms of functional gain (restoration of myocardial perfusion)
Exclusion criteria
do not meet ALL criteria for inclusion * have a concomitant severe disease, at an advanced stage, or with an unquestionable shortening of life expectancy (\<1 year), or that prevents complementary examinations and / or attendance at follow-up visits * have a confirmed diagnosis, previous history and / or past treatment of neoplasia, of any location and staging, in the last 5 years * being in clinical treatment or awaiting surgical treatment of neoplasia, any location and staging * present, during the outpatient investigation, unequivocal findings of neoplasia * have symptoms attributable exclusively to left ventricular dysfunction, although of ischemic etiology, without the evidence of current myocardial ischemia, by at least two (2) methods of evaluation * presented severe left ventricular dysfunction as defined by transthoracic echocardiography due to the finding of a left ventricular ejection fraction \<0.25 (Simpson's method) * have a history or current diagnosis of severe ventricular arrhythmias such as sustained ventricular tachycardia unless an automatic cardioverter-defibrillator has been implanted previously * Concurrent heart diseases of other etiologies (valvular, idiopathic, hypertensive, Chagasic, etc.). * have a history of acute coronary syndrome (unstable angina or acute myocardial infarction) in the last 3 months * present chronic renal failure in dialysis treatment * have participated in other cell therapy studies in the past 2 years * Pregnant women * patients diagnosed with acquired immunodeficiency syndrome (AIDS)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unplanned myocardial revascularization surgery | 12 months | Need for urgent surgical myocardial revascularization |
| Unplanned myocardial revascularization through angioplasty | 12 months | Need for urgent non-surgical myocardial revascularization |
| Cardiovascular Death | 12 months | Death due to stroke, myocardial infarction or other cardiovascular causes |
| Unstable angina | 12 months | Occurence of angina requiring hospitalization |
| Acute myocardial infarction | 12 months after procedure | Occurence of acute myocardial infarction (with or without ST segment elevation) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurence of acute pulmonary edema | 12 months | — |
| Pulmonary embolism | 12 months | — |
| All cause mortality | 12 months | — |
| Septic shock | 12 months | Disseminated infection requiring vasopressors |
| New onset cancer | 12 month | Diagnosis of any cancer at any stage during study period |
| Acute respiratory failure of any cause | 12 months | — |
| Stroke | 12 months | — |
| Cardiogenic shock | 12 months | — |
| Occurence of complex ventricular arrhythmia | 12 months | — |
| New onset atrial fibrilation | 12 months | — |
Outcome results
None listed