Intramyocardial Delivery of Autologous Bone Marrow

Refractory Angina Clinical Trial

Official title:

Intramyocardial Delivery of Autologous Bone Marrow

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT00820586
• Other study ID #: TVICPR-003
• Status: Suspended
• Phase: Phase 2
• First received: January 8, 2009
• Last updated: February 1, 2012
• Start date: May 2007
• Est. completion date: December 2018

Study information

• Verified date: February 2012
• Source: IRCCS San Raffaele
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Institute of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 13
• Est. completion date: December 2018
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Refractory Angina

Intervention

Procedure:
• Mononuclear bone marrow derived cells
Direct intramyocardial percutaneous delivery of autologous bone marrow-derived total mononuclear cells or selected CD34+ cells

Locations

Country	Name	City	State
Italy	IRCCS S. Raffaele	Milan

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS San Raffaele

Country where clinical trial is conducted

Italy, 

References & Publications (35)

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* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Change in Canadian Cardiovascular Society (CCS) angina classification score		12 months	No
Secondary	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	No
Secondary	Change in exercise duration and exercise tolerance using standardized treadmill exercise testing		6,12 months	No
Secondary	Cumulative number of hospitalizations for coronary ischemia and congestive heart failure		12 months	Yes
Secondary	SPECT-chances in global and regional radionuclide perfusion at rest, peak stress, and redistribution		1, 6, 12 months	No
Secondary	Change in angiographic collateral score		6 months	No
Secondary	Change in global and regional myocardial contractility (assessed by echocardiography)		6, 12 months	No