Clinical trial NCT00820586: Intramyocardial Delivery of Autologous Bone Marrow
Official title: Intramyocardial Delivery of Autologous Bone Marrow
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Refractory Angina
Keywords: Intramyocardial
Autologous
Bone
Marrow
Randomized
Percutaneous
CD34+
Refractory
Angina
Pectoris.
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2009-01-12
Enrollment: 13
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: 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.
timeFrame: 1, 6, 12 months
Secondary outcomes:
measure: Change in Canadian Cardiovascular Society (CCS) angina classification score
timeFrame: 12 months
measure: Changes in the quality of life, as assessed according to the Seattle Angina Questionnaire
timeFrame: 1,3,6,12 months and every year for 8 years
measure: Change in exercise duration and exercise tolerance using standardized treadmill exercise testing
timeFrame: 6,12 months
measure: Cumulative number of hospitalizations for coronary ischemia and congestive heart failure
timeFrame: 12 months
measure: SPECT-chances in global and regional radionuclide perfusion at rest, peak stress, and redistribution
timeFrame: 1, 6, 12 months
measure: Change in angiographic collateral score
timeFrame: 6 months
measure: Change in global and regional myocardial contractility (assessed by echocardiography)
timeFrame: 6, 12 months
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS S. Raffaele
Study officials:
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