Prospective, Controlled and Randomized Clinical Trial on Cardiac Cell Regeneration With Laser and Autologous Bone Marrow Stem Cells, in Patients With Coronary Disease and Refractory Angina

NCT ID: NCT01214499

Last Updated: 2010-11-30

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

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2012-10-31

Brief Summary

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Coronary disease is one of the most frequent pathology of the modern world and the leading cause of death in the investigators country. In Spain more than 50.000 coronary percutaneous intervention and more than 5.000 coronary artery bypass graft (CABG) procedures are performed every year. Despite this data about 12% of patients have diffuse coronary disease and are not candidates to conventional therapies. Also between 15-25% of patients undergoing coronary bypass grafting receive an incomplete revascularization due to the poor quality of the coronary vessels.

Transmyocardial revascularization (TMR) is a surgical procedure that uses a laser to create channels through the myocardial, so this laser stimulates local angiogenesis and provides blood in the ischemic area. Results of this procedure have shown clear benefits in terms of reduction of angina and increase of survival of patients, compared to medical treatment.

Cell therapy in heart disease is offering in recent years encouraging results despite the methodological difficulties that being able to use this technique sometimes involves. The basis lies in the potential ability of stem cells to differentiate into any type of adult cell. In the case of cardiac cell therapy, stem cells can differentiate into myocardial cells or vascular cells capable of developing angiogenesis. Further studies are needed to draw firm conclusions about the clinical impact that the use of stem cells has on cardiovascular disease.

Recently a system has been developed to create, at the same time and in a simple and effective way, the laser channels and the introduction of stem cells on the edges of these channels. This system called PHOENIX ™ consists of a laser probe capable of creating transmural channels in the myocardium.

Based on the what has just been explained, it is quite possible that the combination of both therapies can increase successful results regarding the reduction in angina these patients need. Initially, and after having some experience with this type of treatment, the results could be analyzed and compared with the results obtained through laser therapy, with the help of a controlled clinical trial, such as the one the investigators are proposing.

Detailed Description

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Conditions

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Angina Coronary Disease

Keywords

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Refractory angina Transmyocardial revascularization Stem cells Diffuse coronary disease not amenable to percutaneous coronary intervention, and angina, despite proper medical treatment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Treatment Control

Transmyocardial revascularization (TMR) with Holmium YAG (yttrium aluminium garnet) laser, according to habitual clinical practice in the Department of Cardiovascular Surgery.

Group Type ACTIVE_COMPARATOR

Transmyocardial revascularization (TMR) with Holmium YAG laser

Intervention Type PROCEDURE

Transmyocardial revascularization (TMR) is a surgical procedure that uses a laser to create channels through the myocardial, so this laser stimulates local angiogenesis and provides blood in the ischemic area.

Experimental Treatment

Transmyocardial revascularization (TMR) with Holmium YAG laser plus the patient's own stem cells extracted from bone marrow.

Group Type EXPERIMENTAL

Transmyocardial revascularization (TMR) with Holmium YAG laser plus the patient's own stem cells extracted from bone marrow.

Intervention Type PROCEDURE

The system called PHOENIXTM consists of a laser probe with Holmium:YAG energy capable of creating transmural channels in the myocardium. Surrounding this fibre 3 needles with side holes are arranged so that the implantation of stem cells is done on the edges of the channel and not on the channel itself. This device is capable of distributing stem cells in those channels created by the laser, carrying out both procedures simultaneously.

Interventions

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Transmyocardial revascularization (TMR) with Holmium YAG laser

Transmyocardial revascularization (TMR) is a surgical procedure that uses a laser to create channels through the myocardial, so this laser stimulates local angiogenesis and provides blood in the ischemic area.

Intervention Type PROCEDURE

Transmyocardial revascularization (TMR) with Holmium YAG laser plus the patient's own stem cells extracted from bone marrow.

The system called PHOENIXTM consists of a laser probe with Holmium:YAG energy capable of creating transmural channels in the myocardium. Surrounding this fibre 3 needles with side holes are arranged so that the implantation of stem cells is done on the edges of the channel and not on the channel itself. This device is capable of distributing stem cells in those channels created by the laser, carrying out both procedures simultaneously.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Patients over 18 years of age.
* Patients with at least one area of myocardial ischemia or chronic myocardial infarction of the left ventricle demonstrated by any imaging technique not amenable to conventional revascularization and angina refractory to medical treatment.
* Ejection fraction\> 25% measured in the six months prior to the procedure.
* Participants must be mentally competent to give consent for inclusion in the clinical trial

Exclusion Criteria

* Patients with unstable angina defined as the need for intravenous nitrates at the time of surgery.
* Recent myocardial infarction (within 15 days before the procedure).
* Patients with decompensated heart failure at the time of surgery.
* Severe or life threatening arrhythmia (ventricular tachycardia or fibrillation) in the week before the procedure.
* Patients requiring some type of concomitant valvular surgery.
* Patients with severe obstructive lung disease criteria who are considered as not capable of bearing general anesthesia
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

OTHER

Sponsor Role lead

Responsible Party

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Cardiovascular Surgery Service, Hospital Universitario de La Princesa

Principal Investigators

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Guillermo Reyes Copa, Physician Doctor

Role: PRINCIPAL_INVESTIGATOR

Cardiovascular Surgey Service, Hospital Universitario de La Princesa

Locations

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Hospital Universitario de La Princesa

Madrid, Madrid, Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Guillermo Reyes Copa, Physician Doctor

Role: CONTACT

Phone: +34915202268

Email: [email protected]

Facility Contacts

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Guillermo Reyes Copa, Physician Doctor

Role: primary

References

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Lopez-Palop R, Moreu J, Fernandez-Vazquez F, Hernandez Antolin R. [Spanish Cardiac Catheterization and Coronary Intervention Registry. 15th official report of the Spanish Society of Cardiology Working Group on Cardiac Catheterization and Interventional Cardiology (1990-2005)]. Rev Esp Cardiol. 2006 Nov;59(11):1146-64. Spanish.

Reference Type BACKGROUND
PMID: 17144990 (View on PubMed)

Mukherjee D, Bhatt DL, Roe MT, Patel V, Ellis SG. Direct myocardial revascularization and angiogenesis--how many patients might be eligible? Am J Cardiol. 1999 Sep 1;84(5):598-600, A8. doi: 10.1016/s0002-9149(99)00387-2.

Reference Type BACKGROUND
PMID: 10482164 (View on PubMed)

Weintraub WS, Jones EL, Craver JM, Guyton RA. Frequency of repeat coronary bypass or coronary angioplasty after coronary artery bypass surgery using saphenous venous grafts. Am J Cardiol. 1994 Jan 15;73(2):103-12. doi: 10.1016/0002-9149(94)90198-8.

Reference Type BACKGROUND
PMID: 8296729 (View on PubMed)

Bridges CR, Horvath KA, Nugent WC, Shahian DM, Haan CK, Shemin RJ, Allen KB, Edwards FH; Society of Thoracic Surgeons. The Society of Thoracic Surgeons practice guideline series: transmyocardial laser revascularization. Ann Thorac Surg. 2004 Apr;77(4):1494-502. doi: 10.1016/j.athoracsur.2004.01.007.

Reference Type BACKGROUND
PMID: 15063304 (View on PubMed)

Allen KB, Dowling RD, Angell WW, Gangahar DM, Fudge TL, Richenbacher W, Selinger SL, Petracek MR, Murphy D. Transmyocardial revascularization: 5-year follow-up of a prospective, randomized multicenter trial. Ann Thorac Surg. 2004 Apr;77(4):1228-34. doi: 10.1016/j.athoracsur.2004.01.008.

Reference Type BACKGROUND
PMID: 15063241 (View on PubMed)

Allen KB, Dowling RD, Schuch DR, Pfeffer TA, Marra S, Lefrak EA, Fudge TL, Mostovych M, Szentpetery S, Saha SP, Murphy D, Dennis H. Adjunctive transmyocardial revascularization: five-year follow-up of a prospective, randomized trial. Ann Thorac Surg. 2004 Aug;78(2):458-65; discussion 458-65. doi: 10.1016/j.athoracsur.2004.04.049.

Reference Type BACKGROUND
PMID: 15276496 (View on PubMed)

Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007 May 28;167(10):989-97. doi: 10.1001/archinte.167.10.989.

Reference Type BACKGROUND
PMID: 17533201 (View on PubMed)

Haider HKh. Bone marrow cells for cardiac regeneration and repair: current status and issues. Expert Rev Cardiovasc Ther. 2006 Jul;4(4):557-68. doi: 10.1586/14779072.4.4.557.

Reference Type BACKGROUND
PMID: 16918274 (View on PubMed)

Haider HKh, Ashraf M. Bone marrow stem cell transplantation for cardiac repair. Am J Physiol Heart Circ Physiol. 2005 Jun;288(6):H2557-67. doi: 10.1152/ajpheart.01215.2004.

Reference Type BACKGROUND
PMID: 15897328 (View on PubMed)

Anversa P, Leri A, Kajstura J, Nadal-Ginard B. Myocyte growth and cardiac repair. J Mol Cell Cardiol. 2002 Feb;34(2):91-105. doi: 10.1006/jmcc.2001.1506.

Reference Type BACKGROUND
PMID: 11851350 (View on PubMed)

Klein HM, Ghodsizad A, Borowski A, Saleh A, Draganov J, Poll L, Stoldt V, Feifel N, Piecharczek C, Burchardt ER, Stockschlader M, Gams E. Autologous bone marrow-derived stem cell therapy in combination with TMLR. A novel therapeutic option for endstage coronary heart disease: report on 2 cases. Heart Surg Forum. 2004;7(5):E416-9. doi: 10.1532/HSF98.20041095.

Reference Type BACKGROUND
PMID: 15799915 (View on PubMed)

Patel AN, Spadaccio C, Kuzman M, Park E, Fischer DW, Stice SL, Mullangi C, Toma C. Improved cell survival in infarcted myocardium using a novel combination transmyocardial laser and cell delivery system. Cell Transplant. 2007;16(9):899-905. doi: 10.3727/096368907783338253.

Reference Type BACKGROUND
PMID: 18293888 (View on PubMed)

Reyes G, Allen KB, Aguado B, Duarte J. Bone marrow laser revascularisation for treating refractory angina due to diffuse coronary heart disease. Eur J Cardiothorac Surg. 2009 Jul;36(1):192-4. doi: 10.1016/j.ejcts.2009.03.022. Epub 2009 Apr 25.

Reference Type BACKGROUND
PMID: 19394846 (View on PubMed)

Karch FE, Lasagna L. Toward the operational identification of adverse drug reactions. Clin Pharmacol Ther. 1977 Mar;21(3):247-54. doi: 10.1002/cpt1977213247.

Reference Type BACKGROUND
PMID: 837643 (View on PubMed)

Other Identifiers

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TMR-SC-02

Identifier Type: -

Identifier Source: org_study_id