Intramyocardial Delivery of Autologous Bone Marrow

Sponsor

IRCCS San Raffaele (Other)

Overall Status

Suspended

CT.gov ID

NCT00820586

Collaborator

(none)

Enrollment

Location

Arms

139

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Refractory Angina	Procedure: Mononuclear bone marrow derived cells	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Intramyocardial Delivery of Autologous Bone Marrow

Study Start Date :

May 1, 2007

Actual Primary Completion Date :

Jan 1, 2011

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

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

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

Outcome Measures

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. [1, 6, 12 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Subjects >21 years old;
Subjects with functional class (CCS) III or IV angina;
Subjects with left ventricular (LV) ejection fraction ³ 30%
Attempted "best" tolerated medical therapy
Clinical signs and symptoms of myocardial ischemia with reversible ischemia on perfusion imaging;
Patient deemed to be a poor candidate or at high surgical risk;
Subject must be able to complete a minimum of 2 minutes but no more than 10 minutes exercise test (Bruce Protocol);
Subject (or their legal guardian) understands the nature of the procedure and provides written consent prior to the procedure;
Subject is willing to comply with specified follow-up evaluations;
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:

Severe obstruction (lumen diameter stenosis > 70%) in a coronary or surgical conduit felt to be solely or partially responsible for angina and myocardial ischemia;
There must be at least one coronary or surgical conduit with < 70% diameter stenosis
Poor candidate for percutaneous coronary intervention of treatment zone
Poor candidates for surgical revascularization procedures, such as inadequate target coronary anatomy or lack of potential surgical conduits.

Exclusion Criteria:

Pregnant women;
Left ventricular ejection fraction <30% as assessed by either echocardiography or left ventriculography;
Severe cardiac heart failure with NYHA functional class III-IV symptoms;
Chronic atrial fibrillation;
Prosthetic aortic valve;
Severe (grade III-IV) mitral or aortic insufficiency;
Wall thickness of <8 mm (defined by echocardiography) of the proposed target region of myocardium;
Severe co-morbidity associated with a reduction in life expectancy of <1 year, such as chronic medical illnesses
Braunwald class II unstable angina
Severe peripheral (or aortic) vascular disease which might increase the risk of vascular complications (perforation, dissection or embolization);
Significant aortic valve pathologic sclerosis or stenosis
LV thrombus (mobile or mural-based) seen on echocardiography;
Recent (within 4 weeks) documented myocardial infarction (Q and/or non-Q wave) defined as CK-MB >3times upper normal level;
Currently enrolled in another investigational device or drug trial that has not completed the required follow-up period;
Thrombocytopenia or history of heparin-induced thrombocytopenia or thrombocytosis
Leukopenia
Leukocytosis
Anemia or erythrocytosis
Active peptic ulcer or active gastrointestinal bleeding;
Chronic renal failure requiring dialysis;
Prior or current malignancy
Other conditions that can significantly affect the bone-marrow
Evidence of concurrent infection (WBC >12.000 mm3, temperature >38.5° C);
Serological of clinical evidence of HIV
Immunotherapy
Abnormal bone-marrow morphology as evident in bone-marrow smear prior to the intervention