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Intramyocardial Delivery of Autologous Bone Marrow

This study has suspended participant recruitment.
(No more funding support for additional procedures)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00820586
First Posted: January 12, 2009
Last Update Posted: February 2, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Antonio Colombo, IRCCS San Raffaele
  Purpose
A randomized study to assess the safety, feasibility and effectiveness of direct intramyocardial percutaneous delivery of autologous bone marrow-derived total mononuclear cells or selected CD34+ cells in patients with refractory angina pectoris.

Condition Intervention Phase
Refractory Angina Procedure: Mononuclear bone marrow derived cells Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Intramyocardial Delivery of Autologous Bone Marrow

Resource links provided by NLM:


Further study details as provided by Antonio Colombo, IRCCS San Raffaele:

Primary Outcome Measures:
  • Incidence of major adverse cardiac events (MACE), defined as a combined endpoint of death, acute MI (Q-wave and non-Q wave), revascularization procedures and peri-procedural complications. [ Time Frame: 1, 6, 12 months ]

Secondary Outcome Measures:
  • Change in Canadian Cardiovascular Society (CCS) angina classification score [ Time Frame: 12 months ]
  • Changes in the quality of life, as assessed according to the Seattle Angina Questionnaire [ Time Frame: 1,3,6,12 months and every year for 8 years ]
  • Change in exercise duration and exercise tolerance using standardized treadmill exercise testing [ Time Frame: 6,12 months ]
  • Cumulative number of hospitalizations for coronary ischemia and congestive heart failure [ Time Frame: 12 months ]
  • SPECT-chances in global and regional radionuclide perfusion at rest, peak stress, and redistribution [ Time Frame: 1, 6, 12 months ]
  • Change in angiographic collateral score [ Time Frame: 6 months ]
  • Change in global and regional myocardial contractility (assessed by echocardiography) [ Time Frame: 6, 12 months ]

Enrollment: 13
Study Start Date: May 2007
Estimated Study Completion Date: December 2018
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mononuclear bone marrow derived cells
Intramyocardial injection of total mononuclear bone marrow derived cells
Procedure: Mononuclear bone marrow derived cells
Direct intramyocardial percutaneous delivery of autologous bone marrow-derived total mononuclear cells or selected CD34+ cells
Other Name: Selected CD34+ bone marrow derived cells
Experimental: Selected CD34+ bone marrow derived cells
Intramyocardial injection of selected CD34+ bone marrow derived cells
Procedure: Mononuclear bone marrow derived cells
Direct intramyocardial percutaneous delivery of autologous bone marrow-derived total mononuclear cells or selected CD34+ cells
Other Name: Selected CD34+ bone marrow derived cells

Detailed Description:

Primary Endpoint: Incidence of major adverse cardiac events (MACE) at 30 days. MACE is defined as a combined endpoint of death, acute MI (Q-wave and non-Q wave), revascularization procedures (percutaneous or surgical), and peri-procedural complications (that is, left ventricular perforation with hemodynamic consequences requiring pericardiocentesis, and stroke).

Incidence of MACE at 3, 6 and 12 months

Secondary Endpoints:

  • Change in Canadian Cardiovascular Society (CCS) angina classification score from baseline to 12 months
  • Changes in the quality of life, as assessed according to the Seattle Angina Questionnaire
  • Change in exercise duration and exercise tolerance using standardized treadmill exercise testing from baseline, to 6 months and to 12 months
  • Cumulative number of hospitalizations for coronary ischemia and congestive heart failure at 12 months following treatment.
  • SPECT-chances in global and regional radionuclide perfusion at rest, peak stress, and redistribution for baseline to 1, 6 and 12 months
  • Change in angiographic collateral score at 6 months
  • Change in global and regional myocardial contractility (assessed by echocardiography) at baseline, 6 and 12 months.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Subjects >21 years old;
  2. Subjects with functional class (CCS) III or IV angina;
  3. Subjects with left ventricular (LV) ejection fraction ³ 30%
  4. Attempted "best" tolerated medical therapy
  5. Clinical signs and symptoms of myocardial ischemia with reversible ischemia on perfusion imaging;
  6. Patient deemed to be a poor candidate or at high surgical risk;
  7. Subject must be able to complete a minimum of 2 minutes but no more than 10 minutes exercise test (Bruce Protocol);
  8. Subject (or their legal guardian) understands the nature of the procedure and provides written consent prior to the procedure;
  9. Subject is willing to comply with specified follow-up evaluations;
  10. Patient must develop angina and a horizontal or down-sloping ST-segment depression of ³ 1 mm during exercise, compared to pre-exercise ST segment, 80 ms from the J point or moderate angina with or without the above ST segment changes.

Angiographic Inclusion Criteria:

  1. Severe obstruction (lumen diameter stenosis > 70%) in a coronary or surgical conduit felt to be solely or partially responsible for angina and myocardial ischemia;
  2. There must be at least one coronary or surgical conduit with < 70% diameter stenosis
  3. Poor candidate for percutaneous coronary intervention of treatment zone
  4. Poor candidates for surgical revascularization procedures, such as inadequate target coronary anatomy or lack of potential surgical conduits.

Exclusion Criteria:

  1. Pregnant women;
  2. Left ventricular ejection fraction <30% as assessed by either echocardiography or left ventriculography;
  3. Severe cardiac heart failure with NYHA functional class III-IV symptoms;
  4. Chronic atrial fibrillation;
  5. Prosthetic aortic valve;
  6. Severe (grade III-IV) mitral or aortic insufficiency;
  7. Wall thickness of <8 mm (defined by echocardiography) of the proposed target region of myocardium;
  8. Severe co-morbidity associated with a reduction in life expectancy of <1 year, such as chronic medical illnesses
  9. Braunwald class II unstable angina
  10. Severe peripheral (or aortic) vascular disease which might increase the risk of vascular complications (perforation, dissection or embolization);
  11. Significant aortic valve pathologic sclerosis or stenosis
  12. LV thrombus (mobile or mural-based) seen on echocardiography;
  13. Recent (within 4 weeks) documented myocardial infarction (Q and/or non-Q wave) defined as CK-MB >3times upper normal level;
  14. Currently enrolled in another investigational device or drug trial that has not completed the required follow-up period;
  15. Thrombocytopenia or history of heparin-induced thrombocytopenia or thrombocytosis
  16. Leukopenia
  17. Leukocytosis
  18. Anemia or erythrocytosis
  19. Active peptic ulcer or active gastrointestinal bleeding;
  20. Chronic renal failure requiring dialysis;
  21. Prior or current malignancy
  22. Other conditions that can significantly affect the bone-marrow
  23. Evidence of concurrent infection (WBC >12.000 mm3, temperature >38.5° C);
  24. Serological of clinical evidence of HIV
  25. Immunotherapy
  26. Abnormal bone-marrow morphology as evident in bone-marrow smear prior to the intervention

Angiographic/Ventriculographic Exclusion Criteria:

  1. LV thrombus (mobile or mural-based) seen on left ventriculography;
  2. Coronary lesions suitable for percutaneous coronary interventions;
  3. Unprotected left main coronary artery disease
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00820586


Locations
Italy
IRCCS S. Raffaele
Milan, Italy, 20132
Sponsors and Collaborators
IRCCS San Raffaele
  More Information

Publications:
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Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res. 1999 Aug 6;85(3):221-8.
Kobayashi T, Hamano K, Li TS, Katoh T, Kobayashi S, Matsuzaki M, Esato K. Enhancement of angiogenesis by the implantation of self bone marrow cells in a rat ischemic heart model. J Surg Res. 2000 Apr;89(2):189-95.
Tomita S, Mickle DA, Weisel RD, Jia ZQ, Tumiati LC, Allidina Y, Liu P, Li RK. Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation. J Thorac Cardiovasc Surg. 2002 Jun;123(6):1132-40.
Shintani S, Murohara T, Ikeda H, Ueno T, Sasaki K, Duan J, Imaizumi T. Augmentation of postnatal neovascularization with autologous bone marrow transplantation. Circulation. 2001 Feb 13;103(6):897-903.
Fuchs S, Baffour R, Zhou YF, Shou M, Pierre A, Tio FO, Weissman NJ, Leon MB, Epstein SE, Kornowski R. Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. J Am Coll Cardiol. 2001 May;37(6):1726-32.
Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP. Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet. 2003 Jan 4;361(9351):47-9.
Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Bone marrow cells regenerate infarcted myocardium. Nature. 2001 Apr 5;410(6829):701-5.
Kamihata H, Matsubara H, Nishiue T, Fujiyama S, Amano K, Iba O, Imada T, Iwasaka T. Improvement of collateral perfusion and regional function by implantation of peripheral blood mononuclear cells into ischemic hibernating myocardium. Arterioscler Thromb Vasc Biol. 2002 Nov 1;22(11):1804-10. Erratum in: Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):212.
Kawamoto A, Tkebuchava T, Yamaguchi J, Nishimura H, Yoon YS, Milliken C, Uchida S, Masuo O, Iwaguro H, Ma H, Hanley A, Silver M, Kearney M, Losordo DW, Isner JM, Asahara T. Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation. 2003 Jan 28;107(3):461-8.
Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T; Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet. 2002 Aug 10;360(9331):427-35.
Assmus B, Schächinger V, Teupe C, Britten M, Lehmann R, Döbert N, Grünwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation. 2002 Dec 10;106(24):3009-17.
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Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Mesquita CT, Rossi MI, Carvalho AC, Dutra HS, Dohmann HJ, Silva GV, Belém L, Vivacqua R, Rangel FO, Esporcatte R, Geng YJ, Vaughn WK, Assad JA, Mesquita ET, Willerson JT. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation. 2003 May 13;107(18):2294-302. Epub 2003 Apr 21.
Fuchs S, Satler LF, Kornowski R, Okubagzi P, Weisz G, Baffour R, Waksman R, Weissman NJ, Cerqueira M, Leon MB, Epstein SE. Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol. 2003 May 21;41(10):1721-4.
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Gepstein L, Goldin A, Lessick J, Hayam G, Shpun S, Schwartz Y, Hakim G, Shofty R, Turgeman A, Kirshenbaum D, Ben-Haim SA. Electromechanical characterization of chronic myocardial infarction in the canine coronary occlusion model. Circulation. 1998 Nov 10;98(19):2055-64.
Kornowski R, Hong MK, Leon MB. Comparison between left ventricular electromechanical mapping and radionuclide perfusion imaging for detection of myocardial viability. Circulation. 1998 Nov 3;98(18):1837-41.
Hamano K, Nishida M, Hirata K, Mikamo A, Li TS, Harada M, Miura T, Matsuzaki M, Esato K. Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trial and preliminary results. Jpn Circ J. 2001 Sep;65(9):845-7.

Responsible Party: Antonio Colombo, Director of Invasive Cardiology Unit, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT00820586     History of Changes
Other Study ID Numbers: TVICPR-003
First Submitted: January 8, 2009
First Posted: January 12, 2009
Last Update Posted: February 2, 2012
Last Verified: February 2012

Keywords provided by Antonio Colombo, IRCCS San Raffaele:
Intramyocardial
Autologous
Bone
Marrow
Randomized
Percutaneous
CD34+
Refractory
Angina
Pectoris.


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