IMPACT-CABG Trial: IMPlantation of Autologous CD133+ sTem Cells in Patients Undergoing CABG

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor:
Collaborators:
Miltenyi Biotec, Inc.
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Maisonneuve-Rosemont Hospital
Information provided by (Responsible Party):
Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier:
NCT01033617
First received: December 14, 2009
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

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 time of coronary artery bypass grafting in patients with chronic ischemic cardiomyopathy.


Condition Intervention Phase
Myocardial Infarct
Heart Failure
Procedure: Injection of stem cells at time of coronary artery bypass grafting
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The IMPlantation of Autologous CD133+ sTem Cells in Patients Undergoing CABG With Left Ventricular Dysfunction: the IMPACT-CABG Study

Resource links provided by NLM:


Further study details as provided by Centre hospitalier de l'Université de Montréal (CHUM):

Primary Outcome Measures:
  • Freedom from Major Adverse Cardiac Event: cardiac death, myocardial infarct, repeat coronary bypass grafting or percutaneous intervention of bypassed artery. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Freedom from major arrhythmia: sustained ventricular tachycardia or survived sudden death. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Regional myocardial perfusion and function assessed by magnetic resonance scans. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Device performance end point: Feasibility to produce from 100ml of bone marrow aspiration a final cell product that contains a target CD133+ cells higher than 0.5 million with a purity superior to 30% and a recovery superior to 10%. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • On symptom severity and quality of life after CABG surgery. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: December 2009
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Saline solution with autologous plasma.
Procedure: Injection of stem cells at time of coronary artery bypass grafting
Following completion of the distal coronary artery bypasses, autologous CD133+ stem cells,or placebo solution containing plasma and indistinguishable will be injected in the myocardium. A total of 2.0 ml with 10-15 injections will be injected.
Other Name: CD133+ autologous stem cells OR placebo solution containing autologous plasma
Experimental: CD133+ stem cells
Autologous CD133+ intramyocardial injection at time of coronary artery bypass grafting.
Procedure: Injection of stem cells at time of coronary artery bypass grafting
Following completion of the distal coronary artery bypasses, autologous CD133+ stem cells,or placebo solution containing plasma and indistinguishable will be injected in the myocardium. A total of 2.0 ml with 10-15 injections will be injected.
Other Name: CD133+ autologous stem cells OR placebo solution containing autologous plasma

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.

Our 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, we will assess the safety, feasibility and functional effect of intra-myocardial injection of highly selected autologous CD133+ bone marrow stem cells to placebo.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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, AND who have undergone diagnostic coronary angiography demonstrating ≥70% diameter narrowing of at least 2 major coronary arteries or branches or ≥50% diameter narrowing of the left main coronary artery.
  • A significant left ventricular systolic dysfunction evaluated by echocardiography or LV angiography (LV ejection fraction ≤45% but ≥25%) due to prior myocardial infarction. This area of left ventricular dysfunction should be akinetic or severely hypokinetic, not dyskinetic or aneurismal, when assessed by echocardiography or LV angiogram. This territory should be irrigated by one or a branch of the three major vascular territories (i.e. right coronary artery, left circumflex, or left anterior descending artery distribution) that will be bypassed during the surgical procedure.
  • No contraindications or exclusions (see below).
  • Willingness to participate and ability to provide informed consent.

Exclusion Criteria:

  • Contraindications to magnetic resonance imaging 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 (thus precluding performance of follow-up MR scans), claustrophobia.
  • Lack of ischemic symptoms (angina) prior to referral for CABG (i.e., patients with only 'silent' ischemia will be excluded).
  • Need for urgent or emergent revascularization.
  • Need 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. troponin), and/or worsening ECG changes.
  • Prior CABG surgery.
  • Stroke within 3 months prior to planned 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 elevation of 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 in the judgment of the attending cardiologist or cardiac surgeon
  • Contra-indication for bone marrow aspiration (Thrombocytopenia <50.000 mm3, INR >2.0, use of antiplatelet agents other than aspirin).
  • 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 hrs prior to surgery and an unexplained white blood cell count in excess of 10,000/mm3
  • Myelodysplastic syndrome (MDS)
  • Significant cognitive impairment
  • Any condition associated with a life expectancy of less than 6 months
  • Patients known allergic reaction or contraindication to any of the component of the CD133+ enriched cells
  • Participation in other studies
  • History of severe ventricular tachy-arrythmias
  • Positive laboratory test results for syphilis, HIV, HBC, HCV, HTLV1 and HTLV2
  • Pregnant woman
  • Inability or unwillingness to provide written informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01033617

Contacts
Contact: Nicolas Noiseux, MD, MSc, FRCSC +1 514-890-8131 noiseuxn@videotron.ca

Locations
Canada, Quebec
Centre de recherche du CHUM (CRCHUM) Recruiting
Montreal, Quebec, Canada, H2W 1T8
Contact: Nicolas Noiseux, MD, MSc, FRCSC    514-890-8131    noiseuxn@videotron.ca   
Contact: Samer Mansour, MD    514-890-8100    msamer@hotmail.com   
Principal Investigator: Nicolas Noiseux, MD, MSc, FRCSC         
Principal Investigator: Samer Mansour, MD         
Principal Investigator: Denis-Claude Roy, MD         
Sub-Investigator: Louis-Mathieu Stevens, MD, PhD         
Sub-Investigator: Ignacio Prieto, MD         
Sub-Investigator: Carl Chartrand-Lefebvre, MD         
Sub-Investigator: Fadi Basile, MD         
Sub-Investigator: Pierre Ghosn, MD         
Sub-Investigator: Joe Helou, MD         
Sponsors and Collaborators
Centre hospitalier de l'Université de Montréal (CHUM)
Miltenyi Biotec, Inc.
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Maisonneuve-Rosemont Hospital
Investigators
Principal Investigator: Nicolas Noiseux, MD, MSc, FRCSC Montreal University
  More Information

No publications provided

Responsible Party: Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier: NCT01033617     History of Changes
Other Study ID Numbers: HD08.147
Study First Received: December 14, 2009
Last Updated: March 25, 2014
Health Authority: Canada: Health Canada

Keywords provided by Centre hospitalier de l'Université de Montréal (CHUM):
Stem cells
Cellular therapy
Myocardial repair

Additional relevant MeSH terms:
Heart Failure
Myocardial Infarction
Ventricular Dysfunction, Left
Ventricular Dysfunction
Heart Diseases
Cardiovascular Diseases
Myocardial Ischemia
Vascular Diseases

ClinicalTrials.gov processed this record on July 22, 2014