Intramyocardial Delivery of Autologous Bone Marrow

Phase 2

Suspended

• Conditions: Refractory Angina
• Interventions: Procedure: Mononuclear bone marrow derived cells

• Registration Number: NCT00820586
• Lead Sponsor: IRCCS San Raffaele

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.

Study Timeline

• Study Start: 2007-05
• Study First Submitted: 2009-01-08
• Study First Submitted QC: 2009-01-08
• Study First Posted: 2009-01-12
• Primary Completion: 2011-01
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-01
• Last Update Posted: 2012-02-02
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 13

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mononuclear bone marrow derived cells	Mononuclear bone marrow derived cells	Intramyocardial injection of total mononuclear bone marrow derived cells
Selected CD34+ bone marrow derived cells	Mononuclear bone marrow derived cells	Intramyocardial injection of selected CD34+ bone marrow derived cells

Primary Outcome Measures

Name	Time	Method
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.	1, 6, 12 months

Secondary Outcome Measures

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

Trial Locations

Locations (1)

IRCCS S. Raffaele; 🇮🇹 Milan, Italy