Intramyocardial Delivery of Autologous Bone Marrow

This study has suspended participant recruitment.
(No more funding support for additional procedures)
Sponsor:
Information provided by (Responsible Party):
Antonio Colombo, IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT00820586
First received: January 8, 2009
Last updated: February 1, 2012
Last verified: February 2012
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Intramyocardial Delivery of Autologous Bone Marrow

Resource links provided by NLM:


Further study details as provided by 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change in Canadian Cardiovascular Society (CCS) angina classification score [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change in exercise duration and exercise tolerance using standardized treadmill exercise testing [ Time Frame: 6,12 months ] [ Designated as safety issue: No ]
  • Cumulative number of hospitalizations for coronary ischemia and congestive heart failure [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • SPECT-chances in global and regional radionuclide perfusion at rest, peak stress, and redistribution [ Time Frame: 1, 6, 12 months ] [ Designated as safety issue: No ]
  • Change in angiographic collateral score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in global and regional myocardial contractility (assessed by echocardiography) [ Time Frame: 6, 12 months ] [ Designated as safety issue: No ]

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

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00820586

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

Publications:

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
Study First Received: January 8, 2009
Last Updated: February 1, 2012
Health Authority: Italy: National Institute of Health

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

ClinicalTrials.gov processed this record on August 28, 2014