Bypass Surgery and CD133 Marrow Cell Injection for Treatment of Ischemic Heart Failure (Cardio133)

This study has been completed.
Sponsor:
Collaborator:
Miltenyi Biotec GmbH
Information provided by:
German Heart Institute
ClinicalTrials.gov Identifier:
NCT00462774
First received: April 18, 2007
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

Cell transplantation for treatment of heart failure is a novel field of translational research that offers the perspective of developing curative approaches by regenerating or "rejuvenating" lost and/or diseased myocardium and inducing growth of new blood vessels. Based on the safety and preliminary efficacy testing in previous trials, a stringent efficacy testing will be performed in this study. Sixty patients who had myocardial infarction in the past and now need bypass surgery for ongoing coronary artery disease will undergo either bypass surgery and placebo treatment or bypass surgery and injection of CD133 bone marrow cells directly in the heart muscle. The study will be fully blinded, i.e. neither the patient nor the surgeon knows what substance is injected (placebo or cell product). Patients will be followed for 6 months and various heart function measurements will be performed.


Condition Intervention Phase
Coronary Artery Disease With Need for Bypass Surgery
Myocardial Ischemia, Angina Pectoris
Congestive Heart Failure
Previous Myocardial Infarction
Procedure: Intramyocardial injection of autologous CD133+ marrow cells
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Evaluierung Eines Therapiemodells Der Autologen Knochenmark-Transplantation Bei Herzerkrankungen Mit Besonderem Schwerpunkt Der Prüfung Verschiedener Progenitorzellen

Resource links provided by NLM:


Further study details as provided by German Heart Institute:

Primary Outcome Measures:
  • Left ventricular ejection fraction at rest, measured six months postoperatively, measured by MRI

Secondary Outcome Measures:
  • Change in LVEF compared with preoperatively and early postoperatively
  • Regional contractility in the AOI
  • Physical exercise capacity determined by 6 minute walk test
  • Perfusion in the AOI
  • Change in LV dimensions
  • NYHA and CCS class
  • Minnesota Living with Heart Failure Score
  • Death, myocardial infarction, or need for reintervention during follow-up

Enrollment: 60
Study Start Date: April 2007
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Detailed Description:

Beginning in 2001, a phase-1 equivalent feasibility and safety evaluation of intramyocardial injection of autologous CD133+ bone marrow cells during elective CABG surgery was conducted at Rostock University. No procedure-related adverse events were observed and there was some improvement of myocardial contractility and perfusion. It was decided to proceed with a controlled efficacy testing, comparing the outcome of standard CABG surgery with that after CABG and CD133+ cell injection. The results of that study indicate that the additional cell injection yields a better left ventricular contractility than CABG alone (LVEF = 47.1±8% vs. 41.3±9% at 6 months). Although this result is encouraging, the trial had several limitations that hamper interpretation of the data. Most notably, no sham-injection of placebo material was performed in the control group, and standard 2D echocardiography served as the only measurement of global LV contractility. A more stringent efficacy testing is needed before large-scale clinical multicenter trials are justified.

Therefore, a prospective, full blinded, randomized, and placebo-controlled trial will be conducted at Deutsches Herzzentrum Berlin Berlin (DHZB), employing current state-of-the art measurement of global and regional LV contractility by cardiac MRI. The following hypothesis will be tested: "Patients who undergo CABG & CD133+ cell injection do not have a higher LV ejection fraction than patient who undergo CABG alone, measured 6 months after the operation". A power analysis based on the previous trial results indicated that 29 patients per group need to be enrolled so as to reject the null-hypothesis with sufficient statistical power. A total of 60 patients will therefore be enrolled in the study and will be randomized to undergo either CABG surgery and injection of placebo or in conjunction with intramyocardial injection of autologous CD133+ enriched bone marrow cells. Bone marrow will be harvested one day prior to surgery and a CD133-enriched cell product (or placebo) will be prepared on-campus. The following day, bypass surgery will be performed and the study substance will be injected in the border zone of the infarcted myocardium. Random allocation will be performed in the cell production facility, so that neither the patient nor the surgeon nor any of the persons involved in follow-up examinations will know whether the cell product or placebo was administered. The primary outcome parameter (LVEF at 6 months) will be measured by cardiac MRI, and secondary outcome parameters include myocardial perfusion, exercise capacity, and quality-of-life assessment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Coronary artery disease with indication for CABG surgery
  • Reduced global left ventricular ejection fraction by transthoracic echocardiography at rest (EF ≤ 35%)
  • Presence of a localized akinetic/hypokinetic/hypoperfused area of LV myocardium for defining the target area
  • Informed consent of the patient
  • Age > 18 years

Exclusion Criteria:

  • Emergency operation
  • Presence of aortic valve disease requiring concomitant valve replacement
  • Debilitating other disease: Degenerative neurologic disorders, psychiatric disease, terminal renal failure requiring dialysis, previous organ transplantation, active malignant neoplasia
  • History of ventricular arrhythmia (≥ Lown III)
  • Impaired ability to comprehend the study information
  • Absent informed written consent
  • Apparent infection (CRP ≥ 20 mg/L, fever (≥38.5° C)
  • Acute myocardial infarction
  • contraindication for MRI assessment
  • Pregnancy or lactation
  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: NCT00462774

Locations
Germany
Deutsches Herzzentrum Berlin
Berlin, Germany, 13353
Sponsors and Collaborators
German Heart Institute
Miltenyi Biotec GmbH
Investigators
Study Director: Roland Hetzer, MD, PhD German Heart Institute
Principal Investigator: Boris Nasseri, MD German Heart Institute
Principal Investigator: Christof Stamm, MD German Heart Institute
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00462774     History of Changes
Other Study ID Numbers: DHZB/CARDIO133/2007/1
Study First Received: April 18, 2007
Last Updated: January 15, 2013
Health Authority: Germany: Ethics Commission
Germany: Paul-Ehrlich-Institut

Keywords provided by German Heart Institute:
Myocardial infarction
Heart failure
Cell therapy
Bone marrow
CD133
Bypass surgery
Stem cells

Additional relevant MeSH terms:
Angina Pectoris
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Failure
Infarction
Ischemia
Myocardial Infarction
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Arteriosclerosis
Arterial Occlusive Diseases
Pathologic Processes
Necrosis

ClinicalTrials.gov processed this record on August 20, 2014