Combined CABG and Stem-Cell Transplantation for Heart Failure - Full Text View

Purpose

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.

Condition	Intervention	Phase
Heart Failure Myocardial Infarction Coronary Artery Disease	Procedure: Coronary bypass operation Procedure: Bone marrow aspiration (crista iliaca) Biological: Intramyocardial mesenchymal stem cell transplantation Biological: Intramyocardial injection of autologous serum	Phase II

MedlinePlus related topics:

Bone Marrow Transplantation Coronary Artery Bypass Surgery Coronary Artery Disease Heart Attack Heart Failure

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Efficacy Study

Official Title:	Combined CABG and Stem-Cell Transplantation for Heart Failure

Further study details as provided by Helsinki University:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
Does a bone marrow transplantation therapy improve BNP-value? [ Time Frame: 3kk, 6 months and 1 year after the procedure ] [ Designated as safety issue: Yes ]
Does a bone marrow transplantation therapy decrease hospitalization or the days stayed in hospital? [ Time Frame: primary hospital stay after the transplantation ] [ Designated as safety issue: No ]
Does pericardial fluid growth factor concentrations correlate to left ventricular function improvement? [ Time Frame: up to 1 year after the translantation ] [ Designated as safety issue: No ]
Does autologous cardiac stem cell quality correlate to left ventricular function improvement? [ Time Frame: 3kk, 6 months and 1 year after the transplantation ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	October 2006
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator Patient group receiving the stem cell injections during the CABG	Procedure: Coronary bypass operation Coronary bypass operation is performed via sternotomy during cardiac arrest. Procedure: Bone marrow aspiration (crista iliaca) 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). Biological: Intramyocardial mesenchymal stem cell transplantation 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)
B: Placebo Comparator The patient group receiving autologous serum injections during the CAGB operation	Procedure: Coronary bypass operation Coronary bypass operation is performed via sternotomy during cardiac arrest. Procedure: Bone marrow aspiration (crista iliaca) 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). Biological: Intramyocardial injection of autologous serum Intramyocardial injection of autologous serum is injected during cardiac arrest

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

General (patients must have all)
- Symptomatic heart failure.
- Scheduled to CABG
- Be 18 to 75 years of age
- Informed Consent obtained
Heart Failure Presentation
- 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.

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00418418

Contacts


Contact: Ari Harjula, MD,PhD	+3585064814	ari.harjula@hus.fi

Contact: Tommi Pätilä, MD	+358504272291	tommi.patila@hus.fi

Locations


Finland
	Department of Cardiothoracic Surgery, Meilahti Hospital	Recruiting
	Helsinki, Finland, 00029-HUS
	Contact: Ari Harjula, MD, PhD +5042764814 ari.harjula@hus.fi
	Contact: Tommi Pätilä, MD, PhD +358504272291 tommi.patila@hus.fi
	Principal Investigator: Ari Harjula, MD, PhD
	Principal Investigator: Tommi Pätilä, MD
	Principal Investigator: Sinisalo Juha, MD, PhD
	Principal Investigator: Antti Vento, MD,PhD
	Sub-Investigator: Mika Laine, MD,PhD
	Sub-Investigator: Pekka Hämmäinen, MD, PhD
	Sub-Investigator: Esko Kankuri, MD, PhD
	Sub-Investigator: Reino Pöyhiä, MD, PhD
	Sub-Investigator: Raili Suojaranta-Ylinen, MD, PhD
	Sub-Investigator: Aapo Ahonen, MD, PhD
	Sub-Investigator: Jorma Sipponen, MD, PhD
	Sub-Investigator: Markku Kupari, MD, PhD
	Sub-Investigator: Riitta Alitalo, MD; PhD

Sponsors and Collaborators

Helsinki University

Investigators


Principal Investigator:	Ari Harjula, MD; PhD	Department of Cardiothoracic Surgery, Helsinki University MeilahtiHospital

More Information

The Registry of Helsinki and Uusimaa Hospital District This link exits the ClinicalTrials.gov site

Responsible Party:	Helsinki University Hospital ( Reijo Haapiainen )
Study ID Numbers:	TYH 6220
First Received:	January 3, 2007
Last Updated:	August 18, 2008
ClinicalTrials.gov Identifier:	NCT00418418
Health Authority:	Finland: Ministry of Social Affairs and Health

Keywords provided by Helsinki University:

Cell transplantation

Heart failure

Clinical trials

Study placed in the following topic categories:

Arterial Occlusive Diseases

Coronary Disease

Necrosis

Heart Failure

Heart Diseases

Myocardial Ischemia

Vascular Diseases

Arteriosclerosis

Ischemia

Infarction

Myocardial Infarction

Coronary Artery Disease

Additional relevant MeSH terms:

Pathologic Processes

Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 23, 2008

Sponsored by:	Helsinki University
Information provided by:	Helsinki University
ClinicalTrials.gov Identifier:	NCT00418418