Adipose Stromal Cells Injection in the Myocardium for Induction of Revascularization

NCT04005989 | Withdrawn Phase 3

• 1 other identifier: ADMIRE
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Conditions

Ischemic Heart Disease; Myocardial Ischemia; Coronary Artery Disease

Keywords

STROMAL CELLS; ADIPOSE STROMAL CELLS; REVASCULARIZATION; MYOCARDIUM REVASCULARIZATION; CARDIAC SURGERY; CORONARY ARTERY DISEASE

Outcome Measures

Primary Outcomes (5)

• Cardiovascular Death

  Death due to stroke, myocardial infarction or other cardiovascular causes

  12 months

• Unstable angina

  Occurence of angina requiring hospitalization

  12 months

• Acute myocardial infarction

  Occurence of acute myocardial infarction (with or without ST segment elevation)

  12 months after procedure

• Unplanned myocardial revascularization surgery

  Need for urgent surgical myocardial revascularization

  12 months

• Unplanned myocardial revascularization through angioplasty

  Need for urgent non-surgical myocardial revascularization

  12 months

Secondary Outcomes (10)

• All cause mortality

  12 months

• Stroke

  12 months

• Cardiogenic shock

  12 months

• Occurence of complex ventricular arrhythmia

  12 months

• New onset atrial fibrilation

  12 months

Study Arms (4)

PLACEBO GROUP

PLACEBO COMPARATOR

injection of saline solution

Biological: Stromal Cells Injection

Low dose group

ACTIVE COMPARATOR

hASC injection (1x10e6 / kg body weight)

Biological: Stromal Cells Injection

Intermediate Dose

ACTIVE COMPARATOR

injection of hASC (2x10e6 / kg of body weight)

Biological: Stromal Cells Injection

High dose group

ACTIVE COMPARATOR

injection of hASC (4x10e6 / kg body weight)

Biological: Stromal Cells Injection

Interventions

Stromal Cells Injection BIOLOGICAL

Adipose stromal cell

High dose group; Intermediate Dose; Low dose group; PLACEBO GROUP

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hospital do Coracao: lead

MeSH Terms

Conditions

Myocardial Ischemia; Coronary Artery Disease

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: DOUBLE BLIND
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: July 2, 2019
• Study Start: December 1, 2021
• Primary Completion: November 30, 2022
• Study Completion: December 20, 2022
• Last Updated: September 22, 2022

Record last verified: 2021-07