Intramyocardial Delivery of Autologous Bone Marrow

February 1, 2012 updated by: Antonio Colombo, IRCCS San Raffaele
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.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20132
        • IRCCS S. Raffaele

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • Selected CD34+ bone marrow derived cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
1, 6, 12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in Canadian Cardiovascular Society (CCS) angina classification score
Time Frame: 12 months
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
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
6,12 months
Cumulative number of hospitalizations for coronary ischemia and congestive heart failure
Time Frame: 12 months
12 months
SPECT-chances in global and regional radionuclide perfusion at rest, peak stress, and redistribution
Time Frame: 1, 6, 12 months
1, 6, 12 months
Change in angiographic collateral score
Time Frame: 6 months
6 months
Change in global and regional myocardial contractility (assessed by echocardiography)
Time Frame: 6, 12 months
6, 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Actual)

January 1, 2011

Study Completion (Anticipated)

December 1, 2018

Study Registration Dates

First Submitted

January 8, 2009

First Submitted That Met QC Criteria

January 8, 2009

First Posted (Estimate)

January 12, 2009

Study Record Updates

Last Update Posted (Estimate)

February 2, 2012

Last Update Submitted That Met QC Criteria

February 1, 2012

Last Verified

February 1, 2012

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • TVICPR-003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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