Combined CABG and Stem-Cell Transplantation for Heart Failure

NCT ID: NCT00418418

Last Updated: 2008-08-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-10-31

Study Completion Date

2010-12-31

Brief Summary

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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

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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.

Conditions

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Heart Failure Myocardial Infarction Coronary Artery Disease

Keywords

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Cell transplantation Heart failure Clinical trials

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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A

Patient group receiving the stem cell injections during the CABG

Group Type ACTIVE_COMPARATOR

Coronary bypass operation

Intervention Type PROCEDURE

Coronary bypass operation is performed via sternotomy during cardiac arrest.

Bone marrow aspiration (crista iliaca)

Intervention Type PROCEDURE

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 transplantation

Intervention Type BIOLOGICAL

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

The patient group receiving autologous serum injections during the CAGB operation

Group Type PLACEBO_COMPARATOR

Coronary bypass operation

Intervention Type PROCEDURE

Coronary bypass operation is performed via sternotomy during cardiac arrest.

Bone marrow aspiration (crista iliaca)

Intervention Type PROCEDURE

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 injection of autologous serum

Intervention Type BIOLOGICAL

Intramyocardial injection of autologous serum is injected during cardiac arrest

Interventions

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Coronary bypass operation

Coronary bypass operation is performed via sternotomy during cardiac arrest.

Intervention Type 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).

Intervention Type PROCEDURE

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)

Intervention Type BIOLOGICAL

Intramyocardial injection of autologous serum

Intramyocardial injection of autologous serum is injected during cardiac arrest

Intervention Type BIOLOGICAL

Other Intervention Names

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CABG Stem cell harvest Stem cell therapy Stem cell control therapy

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Helsinki

OTHER

Sponsor Role lead

Responsible Party

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Helsinki University Hospital

Principal Investigators

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Ari Harjula, MD; PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Cardiothoracic Surgery, Helsinki University MeilahtiHospital

Locations

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Department of Cardiothoracic Surgery, Meilahti Hospital

Helsinki, , Finland

Site Status RECRUITING

Countries

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Finland

Central Contacts

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Ari Harjula, MD,PhD

Role: CONTACT

Phone: +3585064814

Email: [email protected]

Tommi Pätilä, MD

Role: CONTACT

Phone: +358504272291

Email: [email protected]

Facility Contacts

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Ari Harjula, MD, PhD

Role: primary

Tommi Pätilä, MD, PhD

Role: backup

References

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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.

Reference Type DERIVED
PMID: 25142068 (View on PubMed)

Patila 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.

Reference Type DERIVED
PMID: 24656645 (View on PubMed)

Other Identifiers

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TYH 6220

Identifier Type: -

Identifier Source: org_study_id