Trial Outcomes & Findings for Study Protocol of Intramyocardial Injection of Autologous Bone Marrow Stem Cells for Refractory Angina (NCT NCT01966042)

NCT ID: NCT01966042

Last Updated: 2014-06-03

Results Overview

It was evaluated in accordance with the percentage of participants that change the functional class of angina according to CCSAC (Canadian Cardiovascular Society Angina Classification - description below), after treatment. The functional class of angina was also analyzed as an ordinal variable and the median of the functional class was calculated before and after the procedure, at the time of interest (3, 6 and 12 months post treatment), in comparison to baseline, ie. value at 3 months minus value at baseline. Screening of Functional Graduation of Stable Angina: I - Angina only occurs after a fast or prolonged and strenuous effort during work or recreation. II - Slight limitation to everyday activities. III - Considerable limitation of common physical activity. IV - Inability to perform any physical activity without discomfort, the symptoms can be present at rest.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

3, 6 and 12 months

Results posted on

2014-06-03

Participant Flow

Refractory angina patients routinely undergoing treatment at the São Paulo Hospital, in São Paulo, Brazil, a referral tertiary Federal University Hospital for coronary heart disease, were included in the study. The study protocol (ReACT™) was approved by the local and national ethical committee and all patients provided written informed consent.

Refractory angina patients were defined as those with functional class IV (angina at rest) according to the Canadian Cardiovascular Society Angina Classification (CCSAC) despite maximum medical therapy, not suitable for conventional myocardial revascularization and with viable myocardium identification.

Participant milestones

Participant milestones
Measure	Cell Therapy All subjects enrolled in the study underwent bone marrow aspiration and autologous bone marrow mononuclear cells infusion. Local sedation: All subjects enrolled underwent local sedation for bone marrow aspiration. Bone Marrow Aspiration: All subjects enrolled underwent bone marrow aspiration after anesthesia from the posterior iliac crest. The sample was aspirated into sterile syringes and brought to the cell processing laboratory. The processing was in accordance to the Standard Operating Procedure developed observing Good Practice Guidelines. Minithoracotomy: The cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated. Autologous bone marrow mononuclear cells infusion: Once the subject had his or her chest opened, the surgeon drew up the cells into syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium.
Overall Study STARTED	13
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Cell Therapy All subjects enrolled in the study underwent bone marrow aspiration and autologous bone marrow mononuclear cells infusion. Local sedation: All subjects enrolled underwent local sedation for bone marrow aspiration. Bone Marrow Aspiration: All subjects enrolled underwent bone marrow aspiration after anesthesia from the posterior iliac crest. The sample was aspirated into sterile syringes and brought to the cell processing laboratory. The processing was in accordance to the Standard Operating Procedure developed observing Good Practice Guidelines. Minithoracotomy: The cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated. Autologous bone marrow mononuclear cells infusion: Once the subject had his or her chest opened, the surgeon drew up the cells into syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium.
Overall Study Death	2

Baseline Characteristics

Study Protocol of Intramyocardial Injection of Autologous Bone Marrow Stem Cells for Refractory Angina

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cell Therapy n=13 Participants All subjects enrolled in the study underwent bone marrow aspiration and infusion of autologous bone marrow mononuclear cells. Local sedation: All subjects enrolled in the study underwent local sedation for bone marrow aspiration. Bone Marrow Aspiration: All subjects enrolled in the study underwent bone marrow aspiration after anesthesia. Minithoracotomy: The cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated, allowing the good access to the viable myocardial areas. Autologous bone marrow mononuclear cells infusion: Once the subject had his or her chest opened and the coronary anatomy reviewed by examination of the pre-operatory nuclear scan to define the area of ischemia, the surgeon drew up the cells into a series of syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium.
Age, Continuous	64 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Region of Enrollment Brazil	13 participants n=5 Participants

PRIMARY outcome

Timeframe: 3, 6 and 12 months

Outcome measures

Outcome measures
Measure	Cell Therapy n=13 Participants All subjects enrolled in the study underwent bone marrow aspiration and infusion of autologous bone marrow mononuclear cells. Local sedation: All subjects enrolled in the study underwent local sedation for bone marrow aspiration. Bone Marrow Aspiration: All subjects enrolled in the study underwent bone marrow aspiration after anesthesia. Minithoracotomy: The cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated, allowing the good access to the viable myocardial areas. Autologous bone marrow mononuclear cells infusion: Once the subject had his or her chest opened and the coronary anatomy reviewed by examination of the pre-operatory nuclear scan to define the area of ischemia, the surgeon drew up the cells into a series of syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium.
Angina Class Variation Angina Class at 3 Months	-2.0 Angina Classification Standard Deviation 1.1
Angina Class Variation Angina Class at 6 Months	-1.0 Angina Classification Standard Deviation 1.3
Angina Class Variation Angina Class at 12 Months	-0.5 Angina Classification Standard Deviation 0.9
Angina Class Variation Angina Class at Baseline	4.0 Angina Classification Standard Deviation 0.0

SECONDARY outcome

Timeframe: Baseline and 12 months

Analysis of Left Ventricular Ejection Fraction (in %), by echocardiogram.

Outcome measures

Outcome measures
Measure	Cell Therapy n=11 Participants All subjects enrolled in the study underwent bone marrow aspiration and infusion of autologous bone marrow mononuclear cells. Local sedation: All subjects enrolled in the study underwent local sedation for bone marrow aspiration. Bone Marrow Aspiration: All subjects enrolled in the study underwent bone marrow aspiration after anesthesia. Minithoracotomy: The cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated, allowing the good access to the viable myocardial areas. Autologous bone marrow mononuclear cells infusion: Once the subject had his or her chest opened and the coronary anatomy reviewed by examination of the pre-operatory nuclear scan to define the area of ischemia, the surgeon drew up the cells into a series of syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium.
Functional Change Evaluation LVEF at baseline	59.2 percentage of Left Ventrical Ejection Standard Deviation 8.9
Functional Change Evaluation LVEF at 12 months	61.6 percentage of Left Ventrical Ejection Standard Deviation 6.3

SECONDARY outcome

Timeframe: Baseline, 6 and 12 months

Analysis of objective improvement in myocardial ischemia (in %), by stress technetium scintigraphy.

Outcome measures

Outcome measures
Measure	Cell Therapy n=11 Participants All subjects enrolled in the study underwent bone marrow aspiration and infusion of autologous bone marrow mononuclear cells. Local sedation: All subjects enrolled in the study underwent local sedation for bone marrow aspiration. Bone Marrow Aspiration: All subjects enrolled in the study underwent bone marrow aspiration after anesthesia. Minithoracotomy: The cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated, allowing the good access to the viable myocardial areas. Autologous bone marrow mononuclear cells infusion: Once the subject had his or her chest opened and the coronary anatomy reviewed by examination of the pre-operatory nuclear scan to define the area of ischemia, the surgeon drew up the cells into a series of syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium.
Functional Change Evaluation Myocardium Ischemic Area change after 6 months	-15 percentage of area change Standard Deviation 48
Functional Change Evaluation Myocardium Ischemic Area change after 12 months	-100 percentage of area change Standard Deviation 37.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 12 months

Analysis of the variation in life quality questionnaire - Short Form Health Survey (SF-36) was performed. Each domain of the questionnaire was evaluated as a quantitative variable and the medians were retrieved before and after the procedure. The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. It consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e. a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. One patient was lost before answering the questionnaire post procedure.

Outcome measures

Outcome measures
Measure	Cell Therapy n=10 Participants All subjects enrolled in the study underwent bone marrow aspiration and infusion of autologous bone marrow mononuclear cells. Local sedation: All subjects enrolled in the study underwent local sedation for bone marrow aspiration. Bone Marrow Aspiration: All subjects enrolled in the study underwent bone marrow aspiration after anesthesia. Minithoracotomy: The cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated, allowing the good access to the viable myocardial areas. Autologous bone marrow mononuclear cells infusion: Once the subject had his or her chest opened and the coronary anatomy reviewed by examination of the pre-operatory nuclear scan to define the area of ischemia, the surgeon drew up the cells into a series of syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium.
Life Quality Physical Function Pre-procedure	20.0 units on a scale Standard Deviation 27.1
Life Quality Physical Function Post-procedure	72.5 units on a scale Standard Deviation 24.5
Life Quality Role-Physical Pre-procedure	0.0 units on a scale Standard Deviation 31.6
Life Quality Role-Physical Post-procedure	100.0 units on a scale Standard Deviation 33.7
Life Quality Bodily Pain Pre-procedure	11.0 units on a scale Standard Deviation 17.3
Life Quality Bodily Pain Post-procedure	100.0 units on a scale Standard Deviation 35.1
Life Quality General Health Pre-procedure	20.0 units on a scale Standard Deviation 20.0
Life Quality General Health Post-procedure	72.0 units on a scale Standard Deviation 19.7
Life Quality Vitality Pre-procedure	40.0 units on a scale Standard Deviation 22.1
Life Quality Vitality Post-procedure	95 units on a scale Standard Deviation 31.4
Life Quality Social Function Pre-procedure	12.5 units on a scale Standard Deviation 30.3
Life Quality Social Function Post-procedure	100.0 units on a scale Standard Deviation 39.3
Life Quality Role-Emotional Pre-procedure	100.0 units on a scale Standard Deviation 31.6
Life Quality Emotional Post-procedure	100.0 units on a scale Standard Deviation 36.0
Life Quality Mental Health Pre-procedure	70.0 units on a scale Standard Deviation 33.3
Life Quality Mental Health Post-procedure	98.0 units on a scale Standard Deviation 23.9

Adverse Events

Cell Therapy

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cell Therapy n=13 participants at risk All subjects enrolled in the study underwent bone marrow aspiration and infusion of autologous bone marrow mononuclear cells. Local sedation: All subjects enrolled in the study underwent local sedation for bone marrow aspiration. Bone Marrow Aspiration: All subjects enrolled in the study underwent bone marrow aspiration after anesthesia. Minithoracotomy: The cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated, allowing the good access to the viable myocardial areas. Autologous bone marrow mononuclear cells infusion: Once the subject had his or her chest opened and the coronary anatomy reviewed by examination of the pre-operatory nuclear scan to define the area of ischemia, the surgeon drew up the cells into a series of syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium.
Cardiac disorders Inferior myocardial infarction	7.7% 1/13 • Number of events 1 • 6 years
Cardiac disorders Anterior myocardial infarction	7.7% 1/13 • Number of events 1 • 6 years

Other adverse events

Other adverse events
Measure	Cell Therapy n=13 participants at risk All subjects enrolled in the study underwent bone marrow aspiration and infusion of autologous bone marrow mononuclear cells. Local sedation: All subjects enrolled in the study underwent local sedation for bone marrow aspiration. Bone Marrow Aspiration: All subjects enrolled in the study underwent bone marrow aspiration after anesthesia. Minithoracotomy: The cardiac access route was the left anterolateral thoracotomy or left anterior minithoracotomy, depending on the segment of the left ventricle to be treated, allowing the good access to the viable myocardial areas. Autologous bone marrow mononuclear cells infusion: Once the subject had his or her chest opened and the coronary anatomy reviewed by examination of the pre-operatory nuclear scan to define the area of ischemia, the surgeon drew up the cells into a series of syringes and injected the entire contents of the cell preparation in a series of injections directly into the myocardium.
Cardiac disorders Angina	15.4% 2/13 • Number of events 2 • 6 years

Additional Information

Dr. Nelson Americo Hossne Junior

Federal University of Sao Paulo (UNIFESP)

Phone: +55 11 5571-2719

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60