Coronary Artery Disease With Need for Bypass SurgeryPhase 2/3Cardio133NCT00462774
Bypass Surgery and CD133 Marrow Cell Injection for Treatment of Ischemic Heart Failure
A Phase 2/3 study testing Intramyocardial injection of autologous CD133+ marrow cells in people with Coronary Artery Disease With Need for Bypass Surgery and Myocardial Ischemia, Angina Pectoris, run by German Heart Institute at 1 site in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease With Need for Bypass Surgery, Myocardial Ischemia, Angina Pectoris, Congestive Heart Failure
- What is being tested?
- Intramyocardial injection of autologous CD133+ marrow cells
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 60 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2007to Jun 2011
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- Apparent infection (CRP ≥ 20 mg/L, fever (≥38.5° C)
- Acute myocardial infarction
- contraindication for MRI assessment
- Pregnancy or lactation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Coronary Artery Disease With Need for Bypass Surgery, Myocardial Ischemia, Angina Pectoris, Congestive Heart Failure, Previous Myocardial Infarction
- Being tested
- Intramyocardial injection of autologous CD133+ marrow cells
- Keywords
- Myocardial infarction, Heart failure, Cell therapy, Bone marrow, CD133, Bypass surgery, Stem cells
- Medical subject headings
- Myocardial Ischemia, Angina Pectoris, Heart Failure, Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intramyocardial injection of autologous CD133+ marrow cellsProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Left ventricular ejection fraction at rest, measured six months postoperatively, measured by MRI
Secondary outcomes (8)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2007 (estimated)
- Study startApr 2007
- Primary completionJun 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery Disease With Need for Bypass SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- German Heart Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Miltenyi Biomedicine GmbH
- Investigators
- Roland Hetzer, MD, PhD, Study director, German Heart InstituteBoris Nasseri, MD, Principal investigator, German Heart InstituteChristof Stamm, MD, Principal investigator, German Heart Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00462774
- Sponsor's protocol ID
- DHZB/CARDIO133/2007/1
- Acronym
- Cardio133
- Status last verified
- Jan 2013
- First submitted
- 18 Apr 2007
- Last updated
- 16 Jan 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, Schumichen C, Nienaber CA, Freund M, Steinhoff G. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet. 2003 Jan 4;361(9351):45-6. doi: 10.1016/S0140-6736(03)12110-1.
PubMed 12517467Stamm C, Kleine HD, Choi YH, Dunkelmann S, Lauffs JA, Lorenzen B, David A, Liebold A, Nienaber C, Zurakowski D, Freund M, Steinhoff G. Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies. J Thorac Cardiovasc Surg. 2007 Mar;133(3):717-25. doi: 10.1016/j.jtcvs.2006.08.077. Epub 2007 Feb 1.
PubMed 17320570Nasseri BA, Ebell W, Dandel M, Kukucka M, Gebker R, Doltra A, Knosalla C, Choi YH, Hetzer R, Stamm C. Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial. Eur Heart J. 2014 May 14;35(19):1263-74. doi: 10.1093/eurheartj/ehu007. Epub 2014 Feb 3.
PubMed 24497345
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluierung Eines Therapiemodells Der Autologen Knochenmark-Transplantation Bei Herzerkrankungen Mit Besonderem Schwerpunkt Der Prüfung Verschiedener Progenitorzellen
- ClinicalTrials.gov ID
- NCT00462774
- Acronym / sponsor ID
- Cardio133 / DHZB/CARDIO133/2007/1
- Conditions
- Coronary Artery Disease With Need for Bypass Surgery, Myocardial Ischemia, Angina Pectoris, Congestive Heart Failure, Previous Myocardial Infarction
- Keywords
- Myocardial infarction, Heart failure, Cell therapy, Bone marrow, CD133, Bypass surgery, Stem cells
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- German Heart InstituteUniversity, hospital or other
- Collaborators
- Miltenyi Biomedicine GmbH
- Study start
- Apr 2007
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 19 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intramyocardial injection of autologous CD133+ marrow cells | Procedure or surgery | – |
Primary outcome
Left ventricular ejection fraction at rest, measured six months postoperatively, measured by MRI
8 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2013.
- Background: PubMed 12517467Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, Schumichen C, Nienaber CA, Freund M, Steinhoff G. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet. 2003 Jan 4;361(9351):45-6. doi: 10.1016/S0140-6736(03)12110-1.
- Background: PubMed 17320570Stamm C, Kleine HD, Choi YH, Dunkelmann S, Lauffs JA, Lorenzen B, David A, Liebold A, Nienaber C, Zurakowski D, Freund M, Steinhoff G. Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies. J Thorac Cardiovasc Surg. 2007 Mar;133(3):717-25. doi: 10.1016/j.jtcvs.2006.08.077. Epub 2007 Feb 1.
- Derived from this study: PubMed 24497345Nasseri BA, Ebell W, Dandel M, Kukucka M, Gebker R, Doltra A, Knosalla C, Choi YH, Hetzer R, Stamm C. Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial. Eur Heart J. 2014 May 14;35(19):1263-74. doi: 10.1093/eurheartj/ehu007. Epub 2014 Feb 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roland Hetzer, MD, PhD study director
German Heart Institute
Boris Nasseri, MD principal investigator
German Heart Institute
Christof Stamm, MD principal investigator
German Heart Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Intramyocardial injection of autologous CD133+ marrow cells in people with Coronary Artery Disease With Need for Bypass Surgery and Myocardial Ischemia, Angina Pectoris, run by German Heart Institute at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Left ventricular ejection fraction at rest, measured six months postoperatively, measured by MRI. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00462774, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2013.