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

January 15, 2013 updated by: German Heart Institute

Evaluierung Eines Therapiemodells Der Autologen Knochenmark-Transplantation Bei Herzerkrankungen Mit Besonderem Schwerpunkt Der Prüfung Verschiedener Progenitorzellen

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 13353
        • Deutsches Herzzentrum Berlin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Left ventricular ejection fraction at rest, measured six months postoperatively, measured by MRI

Secondary Outcome Measures

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German Heart Institute

Collaborators

Miltenyi Biomedicine 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

April 18, 2007

First Submitted That Met QC Criteria

April 18, 2007

First Posted (Estimate)

April 19, 2007

Study Record Updates

Last Update Posted (Estimate)

January 16, 2013

Last Update Submitted That Met QC Criteria

January 15, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DHZB/CARDIO133/2007/1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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