Adipose Stromal Cells Injection in the Myocardium for Induction of Revascularization (ADMIRE)
Primary Purpose
Ischemic Heart Disease, Myocardial Ischemia, Coronary Artery Disease
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Stromal Cells Injection
Sponsored by
About this trial
This is an interventional treatment trial for Ischemic Heart Disease focused on measuring STROMAL CELLS, ADIPOSE STROMAL CELLS, REVASCULARIZATION, MYOCARDIUM REVASCULARIZATION, CARDIAC SURGERY, CORONARY ARTERY DISEASE
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)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
PLACEBO GROUP
Low dose group
Intermediate Dose
High dose group
Arm Description
injection of saline solution
hASC injection (1x10e6 / kg body weight)
injection of hASC (2x10e6 / kg of body weight)
injection of hASC (4x10e6 / kg body weight)
Outcomes
Primary Outcome Measures
Cardiovascular Death
Death due to stroke, myocardial infarction or other cardiovascular causes
Unstable angina
Occurence of angina requiring hospitalization
Acute myocardial infarction
Occurence of acute myocardial infarction (with or without ST segment elevation)
Unplanned myocardial revascularization surgery
Need for urgent surgical myocardial revascularization
Unplanned myocardial revascularization through angioplasty
Need for urgent non-surgical myocardial revascularization
Secondary Outcome Measures
All cause mortality
Stroke
Cardiogenic shock
Occurence of complex ventricular arrhythmia
New onset atrial fibrilation
Occurence of acute pulmonary edema
Pulmonary embolism
Acute respiratory failure of any cause
Septic shock
Disseminated infection requiring vasopressors
New onset cancer
Diagnosis of any cancer at any stage during study period
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04005989
Brief Title
Adipose Stromal Cells Injection in the Myocardium for Induction of Revascularization
Acronym
ADMIRE
Official Title
Adipose Stromal Cells Injection in the Myocardium for Induction of Revascularization
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Due to logistic issues during COVID-19 pandemic
Study Start Date
December 1, 2021 (Anticipated)
Primary Completion Date
November 30, 2022 (Anticipated)
Study Completion Date
December 20, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital do Coracao
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Heart Disease, Myocardial Ischemia, Coronary Artery Disease
Keywords
STROMAL CELLS, ADIPOSE STROMAL CELLS, REVASCULARIZATION, MYOCARDIUM REVASCULARIZATION, CARDIAC SURGERY, CORONARY ARTERY DISEASE
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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)
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
DOUBLE BLIND
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PLACEBO GROUP
Arm Type
Placebo Comparator
Arm Description
injection of saline solution
Arm Title
Low dose group
Arm Type
Active Comparator
Arm Description
hASC injection (1x10e6 / kg body weight)
Arm Title
Intermediate Dose
Arm Type
Active Comparator
Arm Description
injection of hASC (2x10e6 / kg of body weight)
Arm Title
High dose group
Arm Type
Active Comparator
Arm Description
injection of hASC (4x10e6 / kg body weight)
Intervention Type
Biological
Intervention Name(s)
Stromal Cells Injection
Intervention Description
Adipose stromal cell
Primary Outcome Measure Information:
Title
Cardiovascular Death
Description
Death due to stroke, myocardial infarction or other cardiovascular causes
Time Frame
12 months
Title
Unstable angina
Description
Occurence of angina requiring hospitalization
Time Frame
12 months
Title
Acute myocardial infarction
Description
Occurence of acute myocardial infarction (with or without ST segment elevation)
Time Frame
12 months after procedure
Title
Unplanned myocardial revascularization surgery
Description
Need for urgent surgical myocardial revascularization
Time Frame
12 months
Title
Unplanned myocardial revascularization through angioplasty
Description
Need for urgent non-surgical myocardial revascularization
Time Frame
12 months
Secondary Outcome Measure Information:
Title
All cause mortality
Time Frame
12 months
Title
Stroke
Time Frame
12 months
Title
Cardiogenic shock
Time Frame
12 months
Title
Occurence of complex ventricular arrhythmia
Time Frame
12 months
Title
New onset atrial fibrilation
Time Frame
12 months
Title
Occurence of acute pulmonary edema
Time Frame
12 months
Title
Pulmonary embolism
Time Frame
12 months
Title
Acute respiratory failure of any cause
Time Frame
12 months
Title
Septic shock
Description
Disseminated infection requiring vasopressors
Time Frame
12 months
Title
New onset cancer
Description
Diagnosis of any cancer at any stage during study period
Time Frame
12 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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)
12. IPD Sharing Statement
Learn more about this trial
Adipose Stromal Cells Injection in the Myocardium for Induction of Revascularization
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