Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609001045202
Ethics application status
Approved
Date submitted
2/12/2009
Date registered
8/12/2009
Date last updated
8/12/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
Comparison of intracoronary selected CD 133+ bone marrow stem cells in cardiac recovery after acute myocardial infarct and left ventricular dysfunction: COMPARE-AMI a randomized controlled double blind clinical study
Scientific title
An evaluation of the safety and efficacy of intracoronary selected CD 133+ bone marrow stem cells in cardiac recovery after acute myocardial infarct and left ventricular dysfunction: COMPARE-AMI a randomized controlled double blind clinical study
Secondary ID [1] 1176 0
nil
Universal Trial Number (UTN)
U1111-1112-6736
Trial acronym
COMPARE-AMI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myocardial infarct 252322 0
Heart failure 252358 0
Condition category
Condition code
Cardiovascular 252509 252509 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Early in the morning, bone marrow harvest under local analgesia, up to 100 ml, this takes approximately 60 minutes. Cell processing in the CEll therapy laboratory: CD133+ stem cells purification using the CliniMACS system from Miltenyi Biotech Inc. Later in the same day, and withing 24hrs from bone marrow harvest: intracoronary injection of autologous CD133+ selected stem cells, up to 10 millions cells. This procedure requires percutaneous intervention, requires approximately 60 to 90 minutes.
Intervention code [1] 255627 0
Treatment: Other
Comparator / control treatment
Placebo: intracoronary injection of plasma solution, indistinguishable from cell suspension. These patients will undergo bone marrow aspiration, and intracoronary injection of placebo plasma solution.
Control group
Placebo

Outcomes
Primary outcome [1] 253396 0
Primary safety endpoint:
The change at 4 months in the coronary atherosclerotic burden progression in the proximal and distal to stented segment of the infarct-related artery in treated patients as compared to controls. Intravascular ultrasound (IVUS) and fractional flow reserve (FFR, pressure catheter) are used to characterize the atherosclerotic plaque.
Timepoint [1] 253396 0
4 months after myocardial infarct and injection.
Primary outcome [2] 253397 0
Primary efficacy endpoint:
- The change in global left ventricular ejection fraction (LVEF) at 4 months relative to baseline measured by magnetic resonance imaging
Timepoint [2] 253397 0
4 months after myocardial infarct and injection.
Secondary outcome [1] 262479 0
Device performance end point:
Ability to produce a
final cell product that contains a target CD133+ cells higher than 1x106 with a purity superior to 30% and a recovery superior to 10 %. this is evaluated by flow cytometry (FACs) analysis after processing the bone marrow.
Timepoint [1] 262479 0
Baseline
Secondary outcome [2] 262480 0
Safety:
-The occurrence of a Major Adverse Cardiac Event (MACE) defined as cardiac death, myocardial infarction creatine-kinase (CK) and creatine-kinase-muscle and brain (CK-MB) over 2 times the upper limit of normal), coronary bypass grafting, or a repeat percutaneous intervention of the culprit lesion.
-The occurrence of major arrhythmias defined as sustained ventricular tachycardia or survived sudden death.
Timepoint [2] 262480 0
4 months after myocardial infarct and injection.
Secondary outcome [3] 262481 0
Efficacy:
-Presence of clinically evident heart failure.
-The change in global left ventricular ejection fraction (LVEF) at 4 months relative to baseline measured by quantitative left ventriculography (QLV).
-The change in the infarct area viability at 4 months relative to baseline measured by positron emission tomography (PET) scan.
-The changes in vital signs at follow up (Blood pressure: Systolic, diastolic, mean, Heart rate).
-The number, doses of prescribed heart failure medication (inhibitors of angiotensin-converting enzyme (ACE) or Angiotensin II Receptor Blockers (ARB), B-blockers, Digoxin, Loop diuretics, Spironolactone) and anti-arrhythmic drugs.
-The change in global and regional wall motion score Index measured by quantitative left ventriculography (QLV, centerline method).
-The change in global and regional wall motion score index as measured by resting echocardiography.
-The change in global and regional wall motion score index as measured at maximal dobutamine infusion during low dose dobutamine echocardiography (LDDE).
-The change in magnetic resonance imaging (MRI) assessments (left ventricular (LV) mass, LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF), infarct size = late enhancement volume).
-The change in 99mTc-methoxyisobutyl isonitrile (MIBI) scan (MIBI) assessments ( Resting perfusion defect, LVEF, LVEDV, LVESV).
Timepoint [3] 262481 0
4 months after myocardial infarct and injection.
Secondary outcome [4] 262482 0
Safety and efficacy:
-The occurrence of a Major Adverse Cardiac Event (MACE).
-The change in global and regional wall motion score index as measured by resting echocardiography.
-The change in LVEF relative to baseline measured by resting echo.
-The change in MRI assessments (LV mass, LVEDV, LVESV, LVEF, infarct size measured by the late enhancement volume).
Timepoint [4] 262482 0
12 months after myocardial infarct and injection.

Eligibility
Key inclusion criteria
acute ST-elevation myocardial infarct successfully reperfused by means of coronary stent implantation and demonstrated a substantial persistent LV dysfunction defined by a LVEF <50% but >25% on echocardiography obtained within 48 hours after the successful reperfusion therapy.
Minimum age
30 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
known previous myocardial infarct, cardiogenic shock, chronic cardiomyopathy, liver disease, renal failure, concomitant disease with a life expectancy of less than 1 year, alcohol or drug dependency, contraindication for bone marrow (BM) aspiration, blood transfusion in the previous 24 hours, hematopoietic disease, chronic inflammatory disease, malignancy, stroke in the previous 3 months or transient ischemic attack in the previous 24 hours.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients are screened in our cardiovascular center, after acute myocardial infarct and reperfusion therapy. Patients who fulfill the inclusion criteria are asked for informed consent, this informed consent is for participation in the randomized trial, for bone marrow aspiration, for infusion of stem cell/placebo,and for baseline and follow up testing and clinical visits.
For patient allocation, we use similar sequentially numbered, sealed envelopes. Half of envelopes will contain CD133+ treatment cards, and the remaining half envelopes will contain placebo cards.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Similar sequentially numbered, sealed envelopes. Half of envelopes will contain CD133+ treatment cards, and the remaining half envelopes will contain placebo cards.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
20/11/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment outside Australia
Country [1] 2349 0
Canada
State/province [1] 2349 0
Quebec

Funding & Sponsors
Funding source category [1] 256114 0
Hospital
Name [1] 256114 0
Centre Hospitalier de l'Universite de Montreal
CHUM
Country [1] 256114 0
Canada
Primary sponsor type
Commercial sector/Industry
Name
Miltenyi Biotech Inc.
Address
120 Presidential Way, Suite 305
Woburn, MA 01801
USA
Country
United States of America
Secondary sponsor category [1] 251460 0
None
Name [1] 251460 0
Address [1] 251460 0
Country [1] 251460 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258203 0
Centre Hospitalier de l'universite de Montreal
Ethics committee address [1] 258203 0
3840 St-Urbain St
Montreal, Quebec
H2W 1T8
Canada
Ethics committee country [1] 258203 0
Canada
Date submitted for ethics approval [1] 258203 0
Approval date [1] 258203 0
29/06/2007
Ethics approval number [1] 258203 0
HD05-025

Summary
Brief summary
Our proposed research protocol involves patients presenting an acute myocardial infarction with left ventricular dysfunction. It is a phase II, prospective, randomized, 2 arms, double-blind, placebo-controlled clinical trial recruiting 40 patients to test the safety, feasibility and the functional effect of the intracoronary administration of a selected population of Autologous bone marrow CD133+ cells as compared to placebo.
Following a successful primary or rescue percutaneous intervention (PCI) for an acute myocardial infarct (MI), patients are eligible for inclusion in this study if the following criteria are fulfilled: age between 30 and 75 years, chest pain for more than 30 minutes and less than 24 hours, ST segment elevation >1 mm in 2 consecutive leads in the limb leads or >2 mm in the precordial leads and an increase in CK or CKMB. Patients need to be < 7 days of admission for their acute ST elevation myocardial infarction, have successful stenting of the culprit stenosis with a normal thrombolysis in myocardial infarction (TIMI) flow, a reference lumen >3mm, single vessel disease, an LVEF <50 and >25%, regional wall motion abnormalities (moderate to severe hypokinesia, akinesia, dyskinesia) in at least 2 adjacent segments on the resting Echocardiography obtained within 48 hours after the acute event, clinically and hemodynamically stable over the last 12 hours.
A total of 40 patients in the participating center will be recruited.
Trial website
Trial related presentations / publications
Mansour S, Roy DC, Bouchard V, Nguyen BK, Stevens LM, Gobeil JF, Rivard A, Leclerc G, Noiseux N. COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133+ Bone Marrow Stem Cells to Placebo in Patients After Acute Myocardial Infarction and Left Ventricular Dysfunction: Study Rationale and Design. J. of Cardiovasc. Trans. Res. 2009 in press.

Mansour S, Roy DC, Lemieux B, Ouellet C, Stevens LM, Noiseux N. Stem cell therapy for the broken heart: mini-organ transplantation. Transplant Proc. 2009;41(8):3353-3357.
Public notes

Contacts
Principal investigator
Name 30566 0
Address 30566 0
Country 30566 0
Phone 30566 0
Fax 30566 0
Email 30566 0
Contact person for public queries
Name 13813 0
Dr Samer Monsour/Dr Nicolas Noiseux
Address 13813 0
CHUM
Cardiology
3840 St-Urbain
Montreal, Quebec
Canada
H2W 1T8
Country 13813 0
Canada
Phone 13813 0
+1 514-890-8100
Fax 13813 0
+1 514-412-7212
Email 13813 0
[email protected]/[email protected]
Contact person for scientific queries
Name 4741 0
Dr Samer Monsour/Dr Nicolas Noiseux
Address 4741 0
CHUM
Cardiology
3840 St-Urbain
Montreal, Quebec
Canada
H2W 1T8
Country 4741 0
Canada
Phone 4741 0
+1 514-890-8100
Fax 4741 0
+1 514-412-7212
Email 4741 0
[email protected]/[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseBone marrow cell therapy and cardiac reparability: Better cell characterization will enhance clinical success.2018https://dx.doi.org/10.2217/rme-2017-0134
EmbaseImpact of intracoronary injection of CD133+ bone marrow stem cells on coronary atherosclerotic progression in patients with STEMI: A COMPARE-AMI IVUS substudy.2016https://dx.doi.org/10.1097/MCA.0000000000000302
N.B. These documents automatically identified may not have been verified by the study sponsor.