IMPACT-CABG Trial: IMPlantation of Autologous CD133+ sTem Cells in Patients Undergoing Coronary Artery Bypass Grafting

NCT01467232 | Completed Phase 2 DMC

• 1 other identifier: UHN-CCR-002
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure; Heart Attack; Coronary Artery Bypass Surgery

Outcome Measures

Primary Outcomes (2)

• Freedom from Major Adverse Cardiac Event

  cardiac death, myocardial infarct, repeat coronary bypass grafting or percutaneous intervention of bypassed artery.

  6 months

• Freedom from major arrhythmia

  sustained ventricular tachycardia or survived sudden death.

  6 months

Secondary Outcomes (5)

• Regional myocardial perfusion and function assessed by magnetic resonance scans

  6 months

• Global ventricular function assessed by echocardiographic measures of ejection fraction

  6 months

• Relief of symptom severity after CABG surgery

  6 months

• Device performance end point

  baseline

• Quality of Life after CABG surgery

  6 months

Study Arms (2)

Autologous CD133+ Stem Cells

EXPERIMENTAL

Autologous CD133+ stem cells

Biological: Injection of autologous CD133+ stem cells at the time of coronary artery bypass grafting

Saline solution containing autologous plasma

PLACEBO COMPARATOR

Saline solution containing autologous plasma without CD133+ (indistinguishable from the autologous CD133+ stem cells)

Biological: Injection of autologous CD133+ stem cells at the time of coronary artery bypass grafting

Interventions

Injection of autologous CD133+ stem cells at the time of coronary artery bypass grafting BIOLOGICAL

Following completion of the distal coronary artery bypasses, autologous CD133+ stem cells, or placebo (saline solution containing autologous plasma without CD133+) will be injected into the myocardium.

Also known as: Autologous CD133+ stem cells or placebo solution containing autologous plasma without CD133+

Autologous CD133+ Stem Cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Willingness to participate and ability to provide informed consent.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Miltenyi Biotec, Inc.: collaborator

Study Sites (1)

Peter Munk Cardiac Center/ University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (1)

• 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.

  PMID: 27665225 DERIVED

MeSH Terms

Conditions

Heart Failure; Myocardial Infarction

Interventions

AC133 Antigen

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Myocardial Ischemia; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Membrane Glycoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Membrane Proteins

Study Officials

• Terrence M Yau, MD

  Peter Munk Cardiac Centre / University Health Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2011
• First Posted: November 8, 2011
• Study Start: September 1, 2011
• Primary Completion: November 1, 2014
• Study Completion: October 1, 2015
• Last Updated: December 2, 2015

Record last verified: 2015-11

Locations

CA (1)