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

NCT01214499 | Unknown Phase 2

• 1 other identifier: TMR-SC-02
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Angina; Coronary Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• New York Heart Association (NYHA)classification for angina

  The main variable under study is the percentage of patients achieving a decrease in two levels of the NYHA classification for angina.

  one year

Secondary Outcomes (3)

• The demographic, intra and postoperative variables

  one year

• Tests

  one year

• Quality of Life

  one year

Study Arms (2)

Treatment Control

ACTIVE COMPARATOR

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

Procedure: Transmyocardial revascularization (TMR) with Holmium YAG laser

Experimental Treatment

EXPERIMENTAL

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

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

Interventions

Transmyocardial revascularization (TMR) with Holmium YAG laser 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.

Treatment Control

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

Experimental Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Fundación de Investigación Biomédica - Hospital Universitario de La Princesa: lead

Study Sites (1)

Hospital Universitario de La Princesa

Madrid, Madrid, 28006, Spain

RECRUITING

Related Publications (14)

• 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.

  PMID: 17144990 BACKGROUND

• 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.

  PMID: 10482164 BACKGROUND

• 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.

  PMID: 8296729 BACKGROUND

• 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.

  PMID: 15063304 BACKGROUND

• 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.

  PMID: 15063241 BACKGROUND

• 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.

  PMID: 15276496 BACKGROUND

• 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.

  PMID: 17533201 BACKGROUND

• 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.

  PMID: 16918274 BACKGROUND

• 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.

  PMID: 15897328 BACKGROUND

• 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.

  PMID: 11851350 BACKGROUND

• 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.

  PMID: 15799915 BACKGROUND

• 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.

  PMID: 18293888 BACKGROUND

• 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.

  PMID: 19394846 BACKGROUND

• 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.

  PMID: 837643 BACKGROUND

MeSH Terms

Conditions

Angina Pectoris; Coronary Disease

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Guillermo Reyes Copa, Physician Doctor

  Cardiovascular Surgey Service, Hospital Universitario de La Princesa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guillermo Reyes Copa, Physician Doctor

CONTACT

+34915202268; guillermo_reyes_copa@yahoo.es

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 3, 2010
• First Posted: October 5, 2010
• Study Start: October 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: November 30, 2010

Record last verified: 2010-11

Locations

ES (1)