Clinical trial NCT01467232: IMPACT-CABG Trial: IMPlantation of Autologous CD133+ sTem Cells in Patients Undergoing Coronary Artery Bypass Grafting
Official title: Implantation of Autologous CD133+ Stem Cells in Patients Undergoing CABG
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Heart Attack
Coronary Artery Bypass Surgery
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Miltenyi Biotec, Inc.
First posted: 2011-11-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Following myocardial infarct, cellular therapy is a potential approach to repopulate the injured myocardium, to treat heart failure and restore cardiac function. The purpose of this study is to assess the safety, feasibility and efficacy of intramyocardial delivery of selected autologous CD133+ bone marrow stem cells at the time of coronary artery bypass grafting in patients with chronic ischemic cardiomyopathy.

Detailed description: CD133+ are well characterized distinct early progenitor group of stem cells that possess high engraftment, pluripotent and angiogenic capacity and proved to be valuable for cardiac repair by promoting neovascularization, inhibition of apoptosis and cardiomyogenesis.

The investigators proposed research protocol involves patients with chronic ischemic heart disease and left ventricular dysfunction undergoing coronary artery bypass grafting (CABG). In this phase II clinical trial, prospective, randomized, 2 arm, double-blind, placebo-controlled study, the investigators will assess the safety, feasibility and functional effect of intra-myocardial injection of highly selected autologous CD133+ bone marrow stem cells to placebo.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 years, and ≤75 years.
* Patients with severe chronic ischemic cardiomyopathy manifested by Canadian Cardiovascular Society (CCS) class II or greater angina, and/or New York Heart Association (NYHA) class II or greater dyspnea, AND who have undergone diagnostic coronary angiography demonstrating ≥70% diameter narrowing of at least two major coronary arteries or branches or ≥50% diameter narrowing of the left main coronary artery.
* Significant left ventricular systolic dysfunction evaluated by echocardiography or LV angiography (LV ejection fraction ≤45% but ≥25%) due to a prior myocardial infarction. This area of left ventricular dysfunction should be akinetic or severely hypokinetic, not dyskinetic or aneurysmal, when assessed by echocardiography or LV angiogram.
* No contraindications or exclusions (see below).
* Willingness to participate and ability to provide informed consent.

Exclusion Criteria:

* contraindications to magnetic resonance imaging (MRI) including presence of an implantable cardiac defibrillator (ICD) or permanent pacemaker (PPM), or cases in which it is anticipated that an ICD or PPM will be implanted prior to the 6 month follow-up or claustrophobia (thus precluding performance of follow-up MRI scans).
* Need for urgent or emergent revascularization.
* Anticipated for concomitant surgical procedure at the time of CABG (e.g. valve repair or replacement, aneurysm resection, etc.).
* Hemodynamically unstable patients, as defined by heart rate ≤40/min or ≥100/min, and/or systolic blood pressure \<90 mmHg or ≥200 mmHg, and/or ongoing need for intravenous inotropic or vasopressor medications.
* Patients with confirmed myocardial infarction within 14 days, and/or rising cardiac biomarker proteins (i.e. CK-MB or troponin), and/or worsening ECG changes.
* Prior CABG surgery.
* Stroke within 3 months prior to plan CABG.
* Immunosuppressive medication (e.g. prednisone, cyclophosphamide, etanercept, etc.)
* Severe chronic renal insufficiency (serum creatinine ≥ 200 mmol/dl or need for dialysis),liver disease, (diagnosis of cirrhosis, chronic hepatitis, or elevated serum transaminases ≥3 times the upper limit of normal), cerebrovascular disease requiring concomitant carotid endarterectomy, peripheral arterial disease (claudication as the primary factor limiting activity), active non-dermatological malignancy requiring on-going treatment, or any other condition that would place the patient at increased risk for complications during the first 6 months after the procedure in the judgement of the attending cardiologist or cardiac surgeon.
* Contra-indication to bone marrow aspiration (Thrombocytopenia \<50,000 mm3, INR \>2.0 ).
* Hemoglobin less than 10g/dL, white blood cell count less than 4,000/mm3, absolute neutrophil count less than 1500/mm3
* Active infection, with a temperature greater than 37.5°C within 48 hours prior to surgery and an unexplained white blood cell count in excess of 10,000/mm3
* Myelodysplastic syndrome
* Significant cognitive impairment
* Any condition associated with a life expectancy of less than 6 months
* Known allergic reaction or contraindication to any of the components of the CD133+ enriched cells
* Participation in other studies
* History of severe ventricular tachyarrhythmia's requiring treatment
* Positive laboratory test results or a history of syphilis, Hepatitis B Virus, Hepatitis C Virus, Human T-Lymphotropic Virus Type 1 and 2, and Human Immunodeficiency Virus.
* Pregnant woman
* Inability or unwillingness to provide written informed consent

Primary outcomes:
measure: Freedom from Major Adverse Cardiac Event
timeFrame: 6 months
measure: Freedom from major arrhythmia
timeFrame: 6 months
Secondary outcomes:
measure: Regional myocardial perfusion and function assessed by magnetic resonance scans
timeFrame: 6 months
measure: Global ventricular function assessed by echocardiographic measures of ejection fraction
timeFrame: 6 months
measure: Relief of symptom severity after CABG surgery
timeFrame: 6 months
measure: Device performance end point
timeFrame: baseline
measure: Quality of Life after CABG surgery
timeFrame: 6 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Peter Munk Cardiac Center/ University Health Network
state: Ontario
Study officials:
affiliation: Peter Munk Cardiac Centre / University Health Network
name: Terrence M Yau, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Noiseux N, Mansour S, Weisel R, Stevens LM, Der Sarkissian S, Tsang K, Crean AM, Larose E, Li SH, Wintersperger B, Vu MQ, Prieto I, Li RK, Roy DC, Yau TM. The IMPACT-CABG trial: A multicenter, randomized clinical trial of CD133+ stem cell therapy during coronary artery bypass grafting for ischemic cardiomyopathy. J Thorac Cardiovasc Surg. 2016 Dec;152(6):1582-1588.e2. doi: 10.1016/j.jtcvs.2016.07.067. Epub 2016 Aug 13.