Clinical trial NCT04005989: Adipose Stromal Cells Injection in the Myocardium for Induction of Revascularization
Official title: Adipose Stromal Cells Injection in the Myocardium for Induction of Revascularization
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Ischemic Heart Disease
Myocardial Ischemia
Coronary Artery Disease
Keywords: STROMAL CELLS
ADIPOSE STROMAL CELLS
REVASCULARIZATION
MYOCARDIUM REVASCULARIZATION
CARDIAC SURGERY
CORONARY ARTERY DISEASE
Lead sponsor: Hospital do Coracao
Sponsor class: OTHER
First posted: 2019-07-02
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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)
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Cardiovascular Death
timeFrame: 12 months
measure: Unstable angina
timeFrame: 12 months
measure: Acute myocardial infarction
timeFrame: 12 months after procedure
measure: Unplanned myocardial revascularization surgery
timeFrame: 12 months
measure: Unplanned myocardial revascularization through angioplasty
timeFrame: 12 months
Secondary outcomes:
measure: All cause mortality
timeFrame: 12 months
measure: Stroke
timeFrame: 12 months
measure: Cardiogenic shock
timeFrame: 12 months
measure: Occurence of complex ventricular arrhythmia
timeFrame: 12 months
measure: New onset atrial fibrilation
timeFrame: 12 months
measure: Occurence of acute pulmonary edema
timeFrame: 12 months
measure: Pulmonary embolism
timeFrame: 12 months
measure: Acute respiratory failure of any cause
timeFrame: 12 months
measure: Septic shock
timeFrame: 12 months
measure: New onset cancer
timeFrame: 12 month
Other outcomes:
Locations:
Study officials:
References: