Heart FailurePhase 2NCT00418418
Combined CABG and Stem-Cell Transplantation for Heart Failure
A Phase 2 study testing Coronary bypass operation, Bone marrow aspiration (crista iliaca) and Intramyocardial mesenchymal stem cell transplantation in people with Heart Failure and Myocardial Infarction, run by University of Helsinki at 1 site in Finland.
Trial summary
This is a prospective double blind trial of intraoperative transmyocardial bone marrow-derived mesenchymal cell transplantation vs placebo in patients with low left ventricular ejection fraction scheduled to coronary bypass operation. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Heart Failure, Myocardial Infarction, Coronary Artery Disease
- What is being tested?
- Coronary bypass operation, Bone marrow aspiration (crista iliaca) and Intramyocardial mesenchymal stem cell transplantation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteFinland
- Study dates
- Oct 2006to Dec 2010
- Phase
- Phase 2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- General (patients must have all)
- Symptomatic heart failure.
- Scheduled to CABG
- Be 18 to 75 years of age
- Informed Consent obtained
- Heart Failure Presentation
Show all 10Show fewer
- Patients of either gender, who has evaluated in cardiovascular laboratory and scheduled to CABG with moderate heart failure, will be eligible
- NYHA II-IV symptoms
- Left ventricular ejection fraction in screening echocardiography 15 to 45%.
- Optimal heart failure medication and coronary medication before operation, containing at least two heart failure drugs: must have ACE-inhibitor, or AT II blocker, and/or b-blocker together with diuretics, digitalis or aldosterone antagonist, and coronary medication: a statin and anticoagulation, either aspirin or clopidogrel.
Who cannot join
- Heart failure due to left ventricular outflow track obstruction (valve problem or HOCM)
- History of life-threatening ventricular arrhythmias or resuscitation, condition which may be repeatable or implanted ICD.
- Stroke or other disabling condition with in 3 months before screening
- Contraindications to coronary angiogram or MRI
- Other serious disease limiting life expectancy
- Participation in an other clinical trial
- Severe valve disease: mitral, aortic, tricuspid or pulmonic stenosis / insufficiency
- Scheduled valve operation
Trial locations and contacts
1 site in 1 country.
Finland1 site, 1 recruiting
- Recruiting
Department of Cardiothoracic Surgery, Meilahti Hospital
Helsinki, 00029-HUS
Ari Harjula, MD, PhD, +5042764814, ari.harjula@hus.fi
Tommi Pätilä, MD, PhD, +358504272291, tommi.patila@hus.fi
About this study
This is a prospective double blind trial of intraoperative transmyocardial bone marrow-derived mesenchymal cell transplantation vs placebo in patients with low left ventricular ejection fraction scheduled to coronary bypass operation.
Read the detailed description
The prevalence of symptomatic heart failure in general population is up to 2% and the prevalence increases rapidly with age. Half of the patients with symptomatic heart failure will die within 4 years of diagnosis.The purpose of this study is to examine the effect of bone marrow-derived stem cell transplantation in left ventricular ejection fraction.
Consecutive patients with systolic heart failure (n=60), with ischemic coronary heart disease, scheduled to by-pass-operation (CABG) will be collected from cardiovascular laboratory and outpatient clinic of Helsinki University Central Hospital. Patients should have heart failure with ejection fraction between 15 to 45%. Randomly patients are selected to receive a stem cell transplantation with best possible heart failure medication, or without cell transplantation. In this study, 30 patients are receiving bone marrow transplantation, and 30 patients are serving as a control population. All patients will receive CABG.The study will be carried out with randomized, double blind techniques for one year. Randomization (in blocks) will be based on a table of random numbers.Bone marrow and patients own serum will be blinded by using colored syringe, so that the doctor transfusing the sample, will not be able to know the nature of the sample. From all patients, a right atrial biopsy will be collected for assessment of autologous cardiac stem cells. Also sample of pericardial fluid will be collected for measures of growth factors.
Comparisons: Preoperatively, patients will be imagined by cardiac ultrasound, cardiac MRI, cardiac PET and SPECT. Serum pro-BNB samples will be collected. Postoperatively at 3 months and 6 months pro-BNB and cardiac ultrasound will be evaluated. At one year cardiac ultrasound, cardiac MRI, cardiac PET and SPECT will be reassessed.
Heart failure and coronary artery disease treatments beside the transplantation will be optimized according to the judgment of the doctors of the outpatients clinic. Primary endpoint of the study is the change of ejection fraction in MRI images.
- Being tested
- Coronary bypass operation, Bone marrow aspiration (crista iliaca), Intramyocardial mesenchymal stem cell transplantation, Intramyocardial injection of autologous serum
- Keywords
- Cell transplantation, Heart failure, Clinical trials
- Medical subject headings
- Heart Failure, Myocardial Infarction, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Coronary bypass operationProcedure or surgery
Also called CABG
Coronary bypass operation is performed via sternotomy during cardiac arrest.
Bone marrow aspiration (crista iliaca)Procedure or surgery
Also called Stem cell harvest
The bone marrow is aspirated from the iliac crest (100ml). During the operation the aspirate is transported to the stem cell laboratory, where the sample is centrifugated through Ficoll(Registered Trademark).
Intramyocardial mesenchymal stem cell transplantationBiological
Also called Stem cell therapy
During the cardiac arrest, stem cells are directly injected to myocardium. The amount of the cells varies individually (5-1000 x 10e6 cells), the cells are diluted in autologous serum (5 ml)
Intramyocardial injection of autologous serumBiological
Also called Stem cell control therapy
Intramyocardial injection of autologous serum is injected during cardiac arrest
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Patient group receiving the stem cell injections during the CABG Receives: Procedure: Coronary bypass operation; Procedure: Bone marrow aspiration (crista iliaca); Biological: Intramyocardial mesenchymal stem cell transplantation |
| B | Placebo comparator | The patient group receiving autologous serum injections during the CAGB operation Receives: Procedure: Coronary bypass operation; Procedure: Bone marrow aspiration (crista iliaca); Biological: Intramyocardial injection of autologous serum |
What is being measured
The primary outcome is the main question the study is designed to answer.
Does a bone marrow transplantation therapy increase the ejection fraction of the heart measured with MRI, when compared with placebo treatment?
Measured: 1 year after the transplantation
Secondary outcomes (5)
Does a bone marrow transplantation therapy increase any cardiac function parameter measured by a an echocardiography, MRI or PET ischemia area, when compared with no treatment group?
Measured: 6 months and 1 year after the procedure
Does a bone marrow transplantation therapy improve BNP-value?
Measured: 3kk, 6 months and 1 year after the procedure
Does a bone marrow transplantation therapy decrease hospitalization or the days stayed in hospital?
Measured: primary hospital stay after the transplantation
Does pericardial fluid growth factor concentrations correlate to left ventricular function improvement?
Measured: up to 1 year after the translantation
Does autologous cardiac stem cell quality correlate to left ventricular function improvement?
Measured: 3kk, 6 months and 1 year after the transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2007 (estimated)
- Study startOct 2006
- Primary completionDec 2009 (estimated)
- Study completionDec 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Helsinki
- Sponsor type
- University, hospital or other
- Investigators
- Ari Harjula, MD; PhD, Principal investigator, Department of Cardiothoracic Surgery, Helsinki University MeilahtiHospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00418418
- Sponsor's protocol ID
- TYH 6220
- Status last verified
- Aug 2008
- First submitted
- 3 Jan 2007
- Last updated
- 19 Aug 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lehtinen M, Patila T, Vento A, Kankuri E, Suojaranta-Ylinen R, Poyhia R, Harjula A; Helsinki BMMC Collaboration. Prospective, randomized, double-blinded trial of bone marrow cell transplantation combined with coronary surgery - perioperative safety study. Interact Cardiovasc Thorac Surg. 2014 Dec;19(6):990-6. doi: 10.1093/icvts/ivu265. Epub 2014 Aug 20.
PubMed 25142068Patila T, Lehtinen M, Vento A, Schildt J, Sinisalo J, Laine M, Hammainen P, Nihtinen A, Alitalo R, Nikkinen P, Ahonen A, Holmstrom M, Lauerma K, Poyhia R, Kupari M, Kankuri E, Harjula A. Autologous bone marrow mononuclear cell transplantation in ischemic heart failure: a prospective, controlled, randomized, double-blind study of cell transplantation combined with coronary bypass. J Heart Lung Transplant. 2014 Jun;33(6):567-74. doi: 10.1016/j.healun.2014.02.009. Epub 2014 Feb 14.
PubMed 24656645
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined CABG and Stem-Cell Transplantation for Heart Failure
- ClinicalTrials.gov ID
- NCT00418418
- Acronym / sponsor ID
- TYH 6220
- Keywords
- Cell transplantation, Heart failure, Clinical trials
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of HelsinkiUniversity, hospital or other
- Study start
- Oct 2006
- Primary completion
- Dec 2009 (estimated)
- Study completion
- Dec 2010 (estimated)
- First posted
- 4 Jan 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.
This is a prospective double blind trial of intraoperative transmyocardial bone marrow-derived mesenchymal cell transplantation vs placebo in patients with low left ventricular ejection fraction scheduled to coronary bypass operation.
Detailed description
The prevalence of symptomatic heart failure in general population is up to 2% and the prevalence increases rapidly with age. Half of the patients with symptomatic heart failure will die within 4 years of diagnosis.The purpose of this study is to examine the effect of bone marrow-derived stem cell transplantation in left ventricular ejection fraction.
Consecutive patients with systolic heart failure (n=60), with ischemic coronary heart disease, scheduled to by-pass-operation (CABG) will be collected from cardiovascular laboratory and outpatient clinic of Helsinki University Central Hospital. Patients should have heart failure with ejection fraction between 15 to 45%. Randomly patients are selected to receive a stem cell transplantation with best possible heart failure medication, or without cell transplantation. In this study, 30 patients are receiving bone marrow transplantation, and 30 patients are serving as a control population. All patients will receive CABG.The study will be carried out with randomized, double blind techniques for one year. Randomization (in blocks) will be based on a table of random numbers.Bone marrow and patients own serum will be blinded by using colored syringe, so that the doctor transfusing the sample, will not be able to know the nature of the sample. From all patients, a right atrial biopsy will be collected for assessment of autologous cardiac stem cells. Also sample of pericardial fluid will be collected for measures of growth factors.
Comparisons: Preoperatively, patients will be imagined by cardiac ultrasound, cardiac MRI, cardiac PET and SPECT. Serum pro-BNB samples will be collected. Postoperatively at 3 months and 6 months pro-BNB and cardiac ultrasound will be evaluated. At one year cardiac ultrasound, cardiac MRI, cardiac PET and SPECT will be reassessed.
Heart failure and coronary artery disease treatments beside the transplantation will be optimized according to the judgment of the doctors of the outpatients clinic. Primary endpoint of the study is the change of ejection fraction in MRI images.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Procedure: Coronary bypass operation, Procedure: Bone marrow aspiration (crista iliaca), Biological: Intramyocardial mesenchymal stem cell transplantationPatient group receiving the stem cell injections during the CABG |
| B | Placebo comparator | Procedure: Coronary bypass operation, Procedure: Bone marrow aspiration (crista iliaca), Biological: Intramyocardial injection of autologous serumThe patient group receiving autologous serum injections during the CAGB operation |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- General (patients must have all)
- Heart Failure Presentation
Key exclusion criteria (8 listed)
- Heart failure due to left ventricular outflow track obstruction (valve problem or HOCM)
- History of life-threatening ventricular arrhythmias or resuscitation, condition which may be repeatable or implanted ICD.
- Stroke or other disabling condition with in 3 months before screening
- Contraindications to coronary angiogram or MRI
- Other serious disease limiting life expectancy
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 |
|---|---|---|
| Coronary bypass operationAlso: CABGCoronary bypass operation is performed via sternotomy during cardiac arrest. | Procedure or surgery | A, B |
| Bone marrow aspiration (crista iliaca)Also: Stem cell harvestThe bone marrow is aspirated from the iliac crest (100ml). During the operation the aspirate is transported to the stem cell laboratory, where the sample is centrifugated through Ficoll(Registered Trademark). | Procedure or surgery | A, B |
| Intramyocardial mesenchymal stem cell transplantationAlso: Stem cell therapyDuring the cardiac arrest, stem cells are directly injected to myocardium. The amount of the cells varies individually (5-1000 x 10e6 cells), the cells are diluted in autologous serum (5 ml) | Biological | A |
| Intramyocardial injection of autologous serumAlso: Stem cell control therapyIntramyocardial injection of autologous serum is injected during cardiac arrest | Biological | B |
Primary outcome
Does a bone marrow transplantation therapy increase the ejection fraction of the heart measured with MRI, when compared with placebo treatment?
Time frame: 1 year after the transplantation
5 secondary outcomes
Does a bone marrow transplantation therapy increase any cardiac function parameter measured by a an echocardiography, MRI or PET ischemia area, when compared with no treatment group?
Time frame: 6 months and 1 year after the procedure
Does a bone marrow transplantation therapy improve BNP-value?
Time frame: 3kk, 6 months and 1 year after the procedure
Does a bone marrow transplantation therapy decrease hospitalization or the days stayed in hospital?
Time frame: primary hospital stay after the transplantation
Does pericardial fluid growth factor concentrations correlate to left ventricular function improvement?
Time frame: up to 1 year after the translantation
Does autologous cardiac stem cell quality correlate to left ventricular function improvement?
Time frame: 3kk, 6 months and 1 year after the transplantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2008.
- Derived from this study: PubMed 25142068Lehtinen M, Patila T, Vento A, Kankuri E, Suojaranta-Ylinen R, Poyhia R, Harjula A; Helsinki BMMC Collaboration. Prospective, randomized, double-blinded trial of bone marrow cell transplantation combined with coronary surgery - perioperative safety study. Interact Cardiovasc Thorac Surg. 2014 Dec;19(6):990-6. doi: 10.1093/icvts/ivu265. Epub 2014 Aug 20.
- Derived from this study: PubMed 24656645Patila T, Lehtinen M, Vento A, Schildt J, Sinisalo J, Laine M, Hammainen P, Nihtinen A, Alitalo R, Nikkinen P, Ahonen A, Holmstrom M, Lauerma K, Poyhia R, Kupari M, Kankuri E, Harjula A. Autologous bone marrow mononuclear cell transplantation in ischemic heart failure: a prospective, controlled, randomized, double-blind study of cell transplantation combined with coronary bypass. J Heart Lung Transplant. 2014 Jun;33(6):567-74. doi: 10.1016/j.healun.2014.02.009. Epub 2014 Feb 14.
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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.
Ari Harjula, MD; PhD principal investigator
Department of Cardiothoracic Surgery, Helsinki University MeilahtiHospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Coronary bypass operation, Bone marrow aspiration (crista iliaca) and Intramyocardial mesenchymal stem cell transplantation in people with Heart Failure and Myocardial Infarction, run by University of Helsinki at 1 site in Finland.
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 10 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 19 Aug 2008. 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 Finland. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ari Harjula, MD,PhD (+3585064814, ari.harjula@hus.fi), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Does a bone marrow transplantation therapy increase the ejection fraction of the heart measured with MRI, when compared with placebo treatment? (time frame: 1 year after the transplantation). 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 NCT00418418, which also lists 2 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 19 Aug 2008.