Adipose Stromal Cells Injection in the Myocardium for Induction of Revascularization

Phase 3

Withdrawn

• Conditions: Myocardial Ischemia; Coronary Artery Disease; Ischemic Heart Disease
• Interventions: Biological: Stromal Cells Injection

• Registration Number: NCT04005989
• Lead Sponsor: Hospital do Coracao

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.

Study Timeline

• Study First Submitted: 2019-06-13
• Study First Submitted QC: 2019-07-01
• Study First Posted: 2019-07-02
• Status Verified: 2021-07
• Study Start: 2021-12-01
• Last Update Submitted: 2022-09-20
• Last Update Posted: 2022-09-22
• Primary Completion: 2022-11-30
• Study Completion: 2022-12-20

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High dose group	Stromal Cells Injection	injection of hASC (4x10e6 / kg body weight)
PLACEBO GROUP	Stromal Cells Injection	injection of saline solution
Intermediate Dose	Stromal Cells Injection	injection of hASC (2x10e6 / kg of body weight)
Low dose group	Stromal Cells Injection	hASC injection (1x10e6 / kg body weight)

Primary Outcome Measures

Name	Time	Method
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)
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

Secondary Outcome Measures

Name	Time	Method
New onset atrial fibrilation	12 months
Occurence of complex ventricular arrhythmia	12 months
All cause mortality	12 months
Stroke	12 months
Cardiogenic shock	12 months
Occurence of acute pulmonary edema	12 months
Pulmonary embolism	12 months
Acute respiratory failure of any cause	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