ACT34-CMI -- Adult Autologous CD34+ Cells

• Sponsor: Caladrius Biosciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00300053
• Collaborator: (none)
• Enrollment: 321
• Locations: 26
• Arms: 3
• Duration (Months): 35
• Patients Per Site: 12.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of intramyocardial injections of CLBS14 in patients with refractory chronic myocardial ischemia.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Ischemia	Biological: CLBS14 (low-dose); Biological: CLBS14 (high-dose); Biological: placebo injection	Phase 2

Detailed Description

This is a double-blind, prospective, randomized, placebo-controlled trial to determine the tolerability, efficacy, safety and dose range of intramyocardial injections of adult autologous CD34+ cells mobilized with granulocyte colony stimulating factor (G-CSF) for the reduction of angina episodes in patients with refractory chronic myocardial ischemia.

Study Design

• Study Type: Interventional
• Actual Enrollment: 321 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A DB, Randomized, Placebo-controlled Study of the Tolerability, Efficacy, Safety, and Dose Range of Intramyocardial CLBS14 for Reduction of Angina Episodes in Patients With Refractory Chronic Myocardial Ischemia (ACT34-CMI)
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CLBS14: Low-Dose Group 10 intramyocardial injections of 0.2 mL each of auto-CD34+ cells at a dose of 1 x 10^5 (=100000) cells/kg bodyweight	Biological: CLBS14 (low-dose); Eligible subjects will receive subcutaneous injections of 5 µg/kg/day G-CSF for 5 days to mobilize CD34+ cells from the bone marrow to the peripheral blood. Mononuclear cells (MNCs) will be collected via apheresis on day 5. On the day of the cell/placebo injection (day 6), the apheresis product will be enriched for CD34+ cells using the Isolex 300i Magnetic Cell Selection System (Baxter Healthcare). Autologous CD34+ cells will be delivered in 10 intramyocardial injections of 0.2 mL at a dose of 1 x 10^5 (=100000) cells/kg bodyweight each using the MyoStar injection catheter (Biosense Webster, Inc.) into the target areas of myocardial ischemia.; Other Names: G-CSF mobilized, autologous CD34+ cells
Experimental: CLBS14: High-Dose Group 10 intramyocardial injections of 0.2 mL each of auto-CD34+ cells at a dose of 5 x 10^5 (=500000) cells/kg bodyweight	Biological: CLBS14 (high-dose); Eligible subjects will receive subcutaneous injections of 5 µg/kg/day G-CSF for 5 days to mobilize CD34+cells from the bone marrow to the peripheral blood. Mononuclear cells (MNCs) will be collected via apheresis on day 5. On the day of the cell/placebo injection (day 6), the apheresis product will be enriched for CD34+ cells using the Isolex 300i Magnetic Cell Selection System (Baxter Healthcare). Autologous CD34+ cells will be delivered in 10 intramyocardial injections of 0.2 mL at a dose of 5 x 10^5 (=500000) cells/kg bodyweight each using the MyoStar injection catheter (Biosense Webster, Inc.) into the target areas of myocardial ischemia.; Other Names: G-CSF mobilized, autologous CD34+ cells
Placebo Comparator: Placebo injection 10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma	Biological: placebo injection; Eligible subjects will receive subcutaneous injections of 5 µg/kg/day G-CSF for 5 days to mobilize CD34+ cells from the bone marrow to the peripheral blood. Mononuclear cells (MNCs) will be collected via apheresis on day 5. On the day of the cell/placebo injection (day 6), the apheresis product will be enriched for CD34+ cells using the Isolex 300i Magnetic Cell Selection System (Baxter Healthcare). Placebo will be delivered in 10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma into the target areas of myocardial ischemia.; Other Names: 0.9% NaCl (saline) in 5% autologous plasma

Outcome Measures

Primary Outcome Measures

1. Number of Angina Episodes Per Week at 6 and 12 Months [6 and 12 months]

   The number of angina episodes were collected via an electronic subject diary for four weeks at Baseline and at 6 and 12 months. The four-week angina episodes (per week mean) were used as the frequency for each visit. A lower number represents fewer angina episodes. A lower number is better.

Secondary Outcome Measures

1. Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise [Change from Baseline to 6 months and change from baseline to 12 months after treatment]

   A modified Bruce Protocol Exercise Treadmill Test was used to evaluate duration of exercise in all subjects.

2. Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels [Baseline and 12 months after treatment]

   The Canadian Cardiovascular Society (CCS) Functional Classification of Angina is as follows: Class I - Angina only during strenuous or prolonged physical activity Class II - Slight limitation, with angina only during vigorous physical activity Class III - Symptoms with everyday living activities, i.e., moderate limitation Class IV - Inability to perform any activity without angina or angina at rest, i.e., severe limitation

3. Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months [Baseline to 6 months after treatment]

   Angina symptoms were evaluated based on the Seattle Angina Questionnaire (SAQ), which was used to analyze the following: physical limitations, angina stability, angina frequency, treatment satisfaction, and disease perception. The SAQ consisted of 11 questions with 5 or 6 possible responses. Responses were ordinal values (1-7, 10, 11, 97, depending on the type of question; no uniform ranges throughout); responses that corresponded to the lowest level of functioning (worse outcomes) were assigned values of 1, while responses that corresponded to higher functioning levels (better outcome) were assigned a higher ordinal value. If the response to any of these questions was 97 it was recoded as a missing value. Each scale can have a scored value ranging from 0 to 100. A larger number is better.

4. Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters [Baseline to 6 months after treatment]

   The Short Form 36 (SF-36) health survey form was used to analyze physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, general mental health, and health transition. Responses were coded as ordinal numbers going from worst (=1) to best (=highest number). These ordinal scores were transformed into scales ranging from 0 to 100. Higher numbers are generally considered better.

5. Change in Anti-anginal Medication (ie, Nitroglycerin) Use [Baseline to 6 months]

   The mean nitroglycerin use per week was analyzed at baseline and 6 months

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Canadian Cardiovascular Society (CCS) functional class III or IV chronic refractory angina

• subjects without control of their angina symptoms, in spite of maximal tolerated doses of anti-anginal drugs, must be on optimal therapy for their angina and on a stable anti-anginal medication regimen for at least 1 month prior to entering the screening period of the study

• identified as unsuitable for conventional revascularization

• recent coronary angiogram (within the last 12 months) to document the coronary anatomy and to verify the revascularization procedures

• subjects must have objective evidence of inducible ischemia or viable myocardium in the potential target injection zone

• a left ventricular ejection fraction equal to or greater than 25% by ECHO or single photon emission computed tomography (SPECT) at screening

• subjects must experience at minimum an average of 7 angina or anginal equivalent episodes per week

• subjects must be able to complete a minimum of 3 minutes but nor more than 10 minutes on a treadmill following the Modified Bruce Protocol

• subjects must experience angina or anginal equivalent episodes during the screening exercise treadmill test

• female subjects must either be no longer capable of reproduction or using medically valid contraception to prevent pregnancy during the study

• subjects must be willing and able to comply with specified follow-up evaluations

Exclusion Criteria:

• predominant congestive heart failure

• myocardial infarction within 60 days of treatment

• successful or partially successful coronary revascularization procedures (any vessel) within 6 months of study enrollment

• placement of a bi-ventricular pacemaker for cardiac resynchronization therapy (CRT) for heart failure in the past 90 days

• documented stroke or transient ischemic attack (TIA) within 60 days of study enrollment

• history of moderate to severe aortic stenosis or severe aortic insufficiency; severe mitral stenosis or severe mitral insufficiency

• prosthetic aortic valve replacement

• evidence of any life-threatening arrhythmia that requires intervention on the 24-hour Holter monitor. Life-threatening arrhythmia that is successfully treated with an implantable cardioverter defibrillator (ICD) is not exclusionary.

• splenomegaly and/or severe co-morbidity associated with a reduction in life expectancy of less than 1 year, such as chronic medical illness (ie, severe chronic obstructive pulmonary disease, renal failure or cancer [exceptions: in-situ skin cancer or fully removed skin cancer other than melanoma, in-situ cervical cancer, or cancer free for 5 years with no history of a stem cell transplant])

• sickle cell disease or sickle cell trait

• platelet count greater than 10% above the upper limit of normal or a platelet count below 100,000 if on Clopidogrel or 50,000 without Clopidogrel

• hematocrit <30%

• serum creatinine >2.5 mg/dL

• any clinically significant laboratory abnormality on screening laboratories

• currently enrolled in another IDE or IND that has not completed the protocol required primary follow-up period (excludes 15 year follow up of gene therapy trials)

• history of alcohol or drug abuse within 3 months of screening

• joint or peripheral vascular disease or neurologic disease that severely limits treadmill walking

• chronic obstructive pulmonary disease that severely limits walking or FEV1 <30% predicted

• females who are pregnant or lactating

• female subjects who are capable of reproduction and will not use medically valid contraception to prevent pregnancy during the study

• subjects who test positive for HIV, hepatitis B or hepatitis C, or are on chronic immunosuppressive medications or have had a prior stem cell transplant

• subjects with a known hypersensitivity to E. coli-derived proteins, or to any component of Neupogen (Filgrastim) or G-CSF

• subjects who have a significant psychiatric disorder or mental disability that could interfere with the subject´s ability to provide informed consent and/or comply with protocol procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiology PC	Birmingham	Alabama	United States	35211
2	Arizona Heart Institute	Phoenix	Arizona	United States	85005
3	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
4	Scripps Memorial Hospital	La Jolla	California	United States	92037
5	Stanford University Hospital and Clinics	Stanford	California	United States	94305
6	Washington Hospital Center	Washington	District of Columbia	United States	20010
7	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
8	University of Florida Health Science Center	Gainesville	Florida	United States	32610
9	University of Florida Health Science Center	Jacksonville	Florida	United States	32209
10	Central Florida Cardiology Group	Orlando	Florida	United States	32803
11	Saint Joseph's Research Institute	Atlanta	Georgia	United States	30342
12	Northwestern University Medical Center, Bluhm Cardiovascluar Institute	Chicago	Illinois	United States	60611
13	Rush University Medical Center	Chicago	Illinois	United States	60612
14	University of Iowa Hospitals & Clinic	Iowa City	Iowa	United States	52242
15	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
16	Caritas Saint Elizabeth's Medical Center	Boston	Massachusetts	United States	02135
17	Abbott Northwestern Hospital	Minneapolis	Minnesota	United States	55407
18	New York Presbyterian Hospital - Columbia University Medical Center	New York	New York	United States	10032
19	New York Presbyterian Hospital - Weill Cornell Medical College of Cornell University	New York	New York	United States	10065
20	The Lindner Clinical Trial Center	Cincinnati	Ohio	United States	45219
21	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45267
22	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
23	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
24	Swedish Heart & Vascular - Swedish Medical Center	Seattle	Washington	United States	98122
25	University of Wisconsin Medical School	Madison	Wisconsin	United States	53792
26	Comprehensive Cardiovascular Care Group	Milwaukee	Wisconsin	United States	53223

Sponsors and Collaborators

• Caladrius Biosciences, Inc.

Investigators

• Study Director: Caladrius Study DIrector, Caladrius Biosciences, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Caladrius Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT00300053
• Other Study ID Numbers: 24779
• First Posted: Mar 8, 2006
• Last Update Posted: Jan 26, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Caladrius Biosciences, Inc.: angina
• Additional relevant MeSH terms: Myocardial Ischemia; Coronary Artery Disease; Ischemia; Lenograstim

Study Results

Participant Flow

Recruitment Details	Enrollment was conducted at 26 clinical sites in the US.
Pre-assignment Detail	Of 321 enrolled subjects, 147 were screen failures. Of 174 subjects who started cell mobilization, 1 did not complete the mobilization due to possible left ventricular mural thrombosis. Of 173 subjects who completed mobilization, 168 were randomized to 1 of 3 treatment groups, of which 1 was discontinued prior to treatment due to coagulopathy.

Arm/Group Title	CLBS14: Low-Dose Group	CLBS14: High-Dose Group	Placebo Control
Arm/Group Description	Intramyocardial injections of auto-CD34+ cells at low dose (1 x 10^5 cells/kg bodyweight)	Intramyocardial injections of auto-CD34+ cells at high dose (5 x 10^5 cells/kg bodyweight)	Intramyocardial placebo injections
Period Title: Overall Study
STARTED	55	56	56
3-Month Evaluation	55	56	54
6-Month Evaluation	54	55	53
COMPLETED	53	53	50
NOT COMPLETED	2	3	6

Baseline Characteristics

Arm/Group Title	CLBS14: Low-Dose Group	CLBS14: High-Dose Group	Placebo Control	Total
Arm/Group Description	Intramyocardial injections of auto-CD34+ cells at low dose (1 x 10^5 cells/kg bodyweight)	Intramyocardial injections of auto-CD34+ cells at high dose (5 x 10^5 cells/kg bodyweight)	Intramyocardial placebo injections	Total of all reporting groups
Overall Participants	55	56	56	167
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.3 (9.1)	59.8 (9.2)	61.8 (8.5)	61.0 (8.9)
Sex: Female, Male (Count of Participants)
Female	9 16.4%	7 12.5%	6 10.7%	22 13.2%
Male	46 83.6%	49 87.5%	50 89.3%	145 86.8%
Region of Enrollment (participants) [Number]
United States	55 100%	56 100%	56 100%	167 100%

Outcome Measures

1. Primary Outcome

Title	Number of Angina Episodes Per Week at 6 and 12 Months
Description	The number of angina episodes were collected via an electronic subject diary for four weeks at Baseline and at 6 and 12 months. The four-week angina episodes (per week mean) were used as the frequency for each visit. A lower number represents fewer angina episodes. A lower number is better.
Time Frame	6 and 12 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population

Arm/Group Title	CLBS14: Low-Dose Group	CLBS14: High-Dose Group	Placebo Control
Arm/Group Description	Intramyocardial injections of auto-CD34+ cells at low dose (1 x 10^5 cells/kg bodyweight)	Intramyocardial injections of auto-CD34+ cells at high dose (5 x 10^5 cells/kg bodyweight)	Intramyocardial placebo injections
Measure Participants	50	50	46
6 months	6.8 (1.1)	8.3 (1.1)	10.9 (1.2)
12 months	6.3 (1.2)	7.2 (1.1)	11.0 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CLBS14: Low-Dose Group, Placebo Control
	Comments	Frequency of angina episodes per week 6 months after treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CLBS14: Low-Dose Group, Placebo Control
	Comments	Frequency of angina episodes per week 12 months after treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CLBS14: High-Dose Group, Placebo Control
	Comments	Frequency of angina episodes per week 6 months after treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.167
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CLBS14: High-Dose Group, Placebo Control
	Comments	Frequency of angina episodes per week 12 months after treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.181
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise
Description	A modified Bruce Protocol Exercise Treadmill Test was used to evaluate duration of exercise in all subjects.
Time Frame	Change from Baseline to 6 months and change from baseline to 12 months after treatment

Outcome Measure Data

Analysis Population Description

ITT population (note that the number of participants analyzed may differ due to missing data)

Arm/Group Title	CLBS14: Low-Dose Group	CLBS14: High-Dose Group	Placebo Control
Arm/Group Description	Intramyocardial injections of auto-CD34+ cells at low dose (1 x 10^5 cells/kg bodyweight)	Intramyocardial injections of auto-CD34+ cells at high dose (5 x 10^5 cells/kg bodyweight)	Intramyocardial placebo injections
Measure Participants	49	48	41
Change from baseline to 6 months	139 (151)	110 (155)	69 (122)
Change from baseline to 12 months	140 (171)	103 (162)	58 (146)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CLBS14: Low-Dose Group, Placebo Control
	Comments	Change from baseline to 6 months
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CLBS14: Low-Dose Group, Placebo Control
	Comments	Change from baseline to 12 months
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CLBS14: High-Dose Group, Placebo Control
	Comments	Change from baseline to 6 months
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.097
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CLBS14: High-Dose Group, Placebo Control
	Comments	Change from baseline to 12 months
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.134
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels
Description	The Canadian Cardiovascular Society (CCS) Functional Classification of Angina is as follows: Class I - Angina only during strenuous or prolonged physical activity Class II - Slight limitation, with angina only during vigorous physical activity Class III - Symptoms with everyday living activities, i.e., moderate limitation Class IV - Inability to perform any activity without angina or angina at rest, i.e., severe limitation
Time Frame	Baseline and 12 months after treatment

Outcome Measure Data

Analysis Population Description

ITT population (note that the number of participants analyzed may differ due to missing data)

Arm/Group Title	CLBS14: Low-Dose Group	CLBS14: High-Dose Group	Placebo Control
Arm/Group Description	Intramyocardial injections of auto-CD34+ cells at low dose (1 x 10^5 cells/kg bodyweight)	Intramyocardial injections of auto-CD34+ cells at high dose (5 x 10^5 cells/kg bodyweight)	Intramyocardial placebo injections
Measure Participants	52	52	46
No change in CCS classification from baseline	16 29.1%	19 33.9%	16 28.6%
Improvement by 1 level (CCS) from baseline	22 40%	17 30.4%	19 33.9%
Improvement by 2 levels (CCS) from baseline	11 20%	12 21.4%	5 8.9%
Worsening by 1 level (CCS) from baseline	2 3.6%	3 5.4%	4 7.1%
Worsening by 2 levels (CCS) from baseline	0 0%	0 0%	0 0%

4. Secondary Outcome

Title	Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months
Description	Angina symptoms were evaluated based on the Seattle Angina Questionnaire (SAQ), which was used to analyze the following: physical limitations, angina stability, angina frequency, treatment satisfaction, and disease perception. The SAQ consisted of 11 questions with 5 or 6 possible responses. Responses were ordinal values (1-7, 10, 11, 97, depending on the type of question; no uniform ranges throughout); responses that corresponded to the lowest level of functioning (worse outcomes) were assigned values of 1, while responses that corresponded to higher functioning levels (better outcome) were assigned a higher ordinal value. If the response to any of these questions was 97 it was recoded as a missing value. Each scale can have a scored value ranging from 0 to 100. A larger number is better.
Time Frame	Baseline to 6 months after treatment

Outcome Measure Data

Analysis Population Description

ITT population (note that the number of participants analyzed may differ due to missing data)

Arm/Group Title	CLBS14: Low-Dose Group	CLBS14: High-Dose Group	Placebo Control
Arm/Group Description	Intramyocardial injections of auto-CD34+ cells at low dose (1 x 10^5 cells/kg bodyweight)	Intramyocardial injections of auto-CD34+ cells at high dose (5 x 10^5 cells/kg bodyweight)	Intramyocardial placebo injections
Measure Participants	49	49	49
Physical limitations scale	12.4 (15.6)	10.5 (17.1)	10.7 (15.2)
Angina stability scale	29.8 (30.1)	25.5 (30.3)	13.8 (31.9)
Angina frequency scale	28.3 (25.3)	21.7 (24.6)	26.0 (24.3)
Treatment satisfaction scale	11.4 (19.5)	10.3 (21.8)	4.9 (19.0)
Disease perception scale	14.4 (23.2)	12.0 (19.4)	15.1 (21.1)

5. Secondary Outcome

Title	Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters
Description	The Short Form 36 (SF-36) health survey form was used to analyze physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, general mental health, and health transition. Responses were coded as ordinal numbers going from worst (=1) to best (=highest number). These ordinal scores were transformed into scales ranging from 0 to 100. Higher numbers are generally considered better.
Time Frame	Baseline to 6 months after treatment

Outcome Measure Data

Analysis Population Description

ITT population (note that the number of participants analyzed may differ due to missing data)

Arm/Group Title	CLBS14: Low-Dose Group	CLBS14: High-Dose Group	Placebo Control
Arm/Group Description	Intramyocardial injections of auto-CD34+ cells at low dose (1 x 10^5 cells/kg bodyweight)	Intramyocardial injections of auto-CD34+ cells at high dose (5 x 10^5 cells/kg bodyweight)	Intramyocardial placebo injections
Measure Participants	50	50	47
Physical functioning	13.7 (18.1)	13.2 (18.4)	7.9 (21.8)
Role-physical	17.5 (35.1)	15.9 (33.6)	19.4 (33.2)
Bodily pain	13.5 (22.1)	13.5 (21.6)	9.4 (25.1)
General health	7.6 (15.5)	6.0 (15.3)	6.3 (15.4)
Vitality	14.6 (18.0)	14.0 (20.7)	8.9 (23.2)
Social functioning	16.8 (24.1)	12.2 (24.3)	12.0 (32.3)
Role emotional	10.7 (43.9)	17.9 (51.8)	9.7 (50.5)
Mental health	6.2 (16.0)	8.4 (17.9)	3.6 (13.6)
Health transition	40.4 (32.5)	32.7 (31.1)	29.6 (30.0)

6. Secondary Outcome

Title	Change in Anti-anginal Medication (ie, Nitroglycerin) Use
Description	The mean nitroglycerin use per week was analyzed at baseline and 6 months
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

ITT population (note that the number of participants analyzed may differ due to missing data)

Arm/Group Title	CLBS14: Low-Dose Group	CLBS14: High-Dose Group	Placebo Control
Arm/Group Description	Intramyocardial injections of auto-CD34+ cells at low dose (1 x 10^5 cells/kg bodyweight)	Intramyocardial injections of auto-CD34+ cells at high dose (5 x 10^5 cells/kg bodyweight)	Intramyocardial placebo injections
Measure Participants	46	50	50
Mean (Standard Deviation) [nitroglycerin use (tablets per week)]	-6.3 (8.1)	-7.3 (9.9)	-4.2 (8.8)

Adverse Events

Adverse Event Reporting Description	The safety population comprises 174 subjects who received at least 1 dose of G-CSF.
Arm/Group Title	CLBS14: Low-Dose Group		CLBS14: High-Dose Group		Placebo Control		No Cell or Placebo Injection
Arm/Group Description	Intramyocardial injections of auto-CD34+ cells at low dose (1 x 10^5 cells/kg bodyweight)		Intramyocardial injections of auto-CD34+ cells at high dose (5 x 10^5 cells/kg bodyweight)		Intramyocardial placebo injections		Cell mobilization with G-CSF started but no cell or placebo injection administered
All Cause Mortality
	CLBS14: Low-Dose Group		CLBS14: High-Dose Group		Placebo Control		No Cell or Placebo Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/56 (0%)		3/56 (5.4%)		0/7 (0%)
Serious Adverse Events
	CLBS14: Low-Dose Group		CLBS14: High-Dose Group		Placebo Control		No Cell or Placebo Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/55 (38.2%)		24/56 (42.9%)		32/56 (57.1%)		5/7 (71.4%)
Blood and lymphatic system disorders
Thrombocytopenia	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Coagulopathy	0/55 (0%)	0	0/56 (0%)	0	0/56 (0%)	0	1/7 (14.3%)	1
Pancytopenia	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Anemia	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	2	0/7 (0%)	0
Hypercoagulation	0/55 (0%)	0	0/56 (0%)	0	0/56 (0%)	0	1/7 (14.3%)	1
Cardiac disorders
Cardiac perforation	1/55 (1.8%)	1	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Cardiac failure congestive	1/55 (1.8%)	3	1/56 (1.8%)	1	2/56 (3.6%)	4	0/7 (0%)	0
Myocardial infarction	3/55 (5.5%)	5	2/56 (3.6%)	3	3/56 (5.4%)	4	3/7 (42.9%)	3
Angina pectoris	8/55 (14.5%)	15	8/56 (14.3%)	12	11/56 (19.6%)	19	0/7 (0%)	0
Cardiac failure	1/55 (1.8%)	1	0/56 (0%)	0	2/56 (3.6%)	3	0/7 (0%)	0
Acute coronary syndrome	0/55 (0%)	0	1/56 (1.8%)	1	1/56 (1.8%)	1	0/7 (0%)	0
Ventricular tachycardia	1/55 (1.8%)	1	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Ventricular fibrillation	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Angina unstable	2/55 (3.6%)	2	2/56 (3.6%)	2	0/56 (0%)	0	0/7 (0%)	0
Atrial fibrillation	2/55 (3.6%)	2	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Bradycardia	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Gastrointestinal disorders
Nausea	2/55 (3.6%)	2	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Vomiting	2/55 (3.6%)	2	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Abdominal pain	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Abdominal discomfort	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Gastrointestinal ulcer hemorrhage	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Colitis ischaemic	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Upper gastrointestinal hemorrhage	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Hematochezia	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Diverticular perforation	1/55 (1.8%)	1	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
General disorders
Chest pain	0/55 (0%)	0	1/56 (1.8%)	4	2/56 (3.6%)	3	0/7 (0%)	0
Ischemic ulcer	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Non-cardiac chest pain	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	2	0/7 (0%)	0
Hepatobiliary disorders
Cholelithiasis	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Infections and infestations
Esophageal candidiasis	1/55 (1.8%)	1	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Pneumonia	1/55 (1.8%)	1	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Septic phlebitis	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Urinary tract infection	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Sepsis	1/55 (1.8%)	1	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Cellulitis	0/55 (0%)	0	0/56 (0%)	0	2/56 (3.6%)	2	0/7 (0%)	0
Osteomyelitis	1/55 (1.8%)	1	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Gastroenteritis viral	1/55 (1.8%)	1	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Injury, poisoning and procedural complications
Vascular access complication	1/55 (1.8%)	1	3/56 (5.4%)	3	2/56 (3.6%)	3	0/7 (0%)	0
Vascular graft occlusion	1/55 (1.8%)	1	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Concussion	1/55 (1.8%)	1	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Road traffic accident	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Device lead damage	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	2	0/7 (0%)	0
Cardiac pacemaker malfunction	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Device dislocation	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Dehydration	1/55 (1.8%)	1	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Hypoglycemia	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Gout	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Musculoskeletal and connective tissue disorders
Tenosynovitis	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Musculoskeletal chest pain	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Nervous system disorders
Cerebrovascular accident	0/55 (0%)	0	1/56 (1.8%)	1	1/56 (1.8%)	1	0/7 (0%)	0
Syncope	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Transient ischemic attack	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Presyncope	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Dizziness postural	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Dizziness	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Psychiatric disorders
Depression	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Renal and urinary disorders
Urinary tract obstruction	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Renal failure acute	1/55 (1.8%)	1	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Reproductive system and breast disorders
Menorrhagia	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory distress	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Hypoxia	0/55 (0%)	0	1/56 (1.8%)	1	1/56 (1.8%)	1	0/7 (0%)	0
Dyspnea	1/55 (1.8%)	1	1/56 (1.8%)	1	1/56 (1.8%)	1	0/7 (0%)	0
Dyspnea exertional	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Pneumonia aspiration	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Acute pulmonary edema	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Sleep apnea syndrome	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Sinus disorder	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Pulmonary embolism	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Pleural effusion	0/55 (0%)	0	1/56 (1.8%)	1	0/56 (0%)	0	0/7 (0%)	0
Respiratory failure	1/55 (1.8%)	2	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Vascular disorders
Hypotension	1/55 (1.8%)	1	2/56 (3.6%)	2	0/56 (0%)	0	0/7 (0%)	0
Deep vein thrombosis (DVT)	1/55 (1.8%)	1	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Aortic aneurysm	1/55 (1.8%)	1	0/56 (0%)	0	0/56 (0%)	0	0/7 (0%)	0
Peripheral arterial occlusive disease	0/55 (0%)	0	0/56 (0%)	0	1/56 (1.8%)	1	0/7 (0%)	0
Other (Not Including Serious) Adverse Events
	CLBS14: Low-Dose Group		CLBS14: High-Dose Group		Placebo Control		No Cell or Placebo Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/55 (98.2%)		52/56 (92.9%)		52/56 (92.9%)		5/7 (71.4%)
Cardiac disorders
Angina Pectoris	20/55 (36.4%)	25	14/56 (25%)	18	12/56 (21.4%)	16	1/7 (14.3%)	1
Palpitations	2/55 (3.6%)	2	4/56 (7.1%)	4	3/56 (5.4%)	3	0/7 (0%)	0
Gastrointestinal disorders
Diarrhea	6/55 (10.9%)	6	5/56 (8.9%)	6	5/56 (8.9%)	5	0/7 (0%)	0
Nausea	13/55 (23.6%)	14	11/56 (19.6%)	16	9/56 (16.1%)	10	0/7 (0%)	0
Vomiting	5/55 (9.1%)	5	4/56 (7.1%)	6	1/56 (1.8%)	1	0/7 (0%)	0
General disorders
Chest Pain	5/55 (9.1%)	5	3/56 (5.4%)	21	2/56 (3.6%)	3	1/7 (14.3%)	1
Fatigue	15/55 (27.3%)	15	9/56 (16.1%)	9	11/56 (19.6%)	11	0/7 (0%)	0
Edema Peripheral	3/55 (5.5%)	3	5/56 (8.9%)	5	6/56 (10.7%)	6	0/7 (0%)	0
Pain	7/55 (12.7%)	8	9/56 (16.1%)	9	6/56 (10.7%)	6	2/7 (28.6%)	2
Infections and infestations
Upper Respiratory Tract Infection	7/55 (12.7%)	9	2/56 (3.6%)	2	4/56 (7.1%)	5	0/7 (0%)	0
Injury, poisoning and procedural complications
Vascular Access Complication	14/55 (25.5%)	22	14/56 (25%)	18	11/56 (19.6%)	22	1/7 (14.3%)	1
Metabolism and nutrition disorders
Hypocalcemia	8/55 (14.5%)	8	9/56 (16.1%)	9	4/56 (7.1%)	4	0/7 (0%)	0
Hypokalemia	4/55 (7.3%)	4	4/56 (7.1%)	4	6/56 (10.7%)	8	2/7 (28.6%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	12/55 (21.8%)	15	12/56 (21.4%)	14	8/56 (14.3%)	9	0/7 (0%)	0
Back Pain	17/55 (30.9%)	18	19/56 (33.9%)	25	11/56 (19.6%)	11	0/7 (0%)	0
Bone Pain	13/55 (23.6%)	13	11/56 (19.6%)	14	10/56 (17.9%)	10	1/7 (14.3%)	1
Musculoskeletal Chest Pain	4/55 (7.3%)	8	3/56 (5.4%)	4	5/56 (8.9%)	5	0/7 (0%)	0
Musculoskeletal Pain	5/55 (9.1%)	7	4/56 (7.1%)	7	0/56 (0%)	0	0/7 (0%)	0
Myalgia	3/55 (5.5%)	3	4/56 (7.1%)	4	4/56 (7.1%)	4	1/7 (14.3%)	1
Neck Pain	2/55 (3.6%)	2	6/56 (10.7%)	6	2/56 (3.6%)	2	0/7 (0%)	0
Pain in Extremity	7/55 (12.7%)	12	7/56 (12.5%)	8	6/56 (10.7%)	7	0/7 (0%)	0
Nervous system disorders
Dizziness	8/55 (14.5%)	8	5/56 (8.9%)	6	6/56 (10.7%)	6	0/7 (0%)	0
Headache	16/55 (29.1%)	20	25/56 (44.6%)	31	10/56 (17.9%)	10	4/7 (57.1%)	4
Paresthesia	12/55 (21.8%)	15	15/56 (26.8%)	15	17/56 (30.4%)	24	2/7 (28.6%)	2
Psychiatric disorders
Anxiety	3/55 (5.5%)	3	4/56 (7.1%)	4	2/56 (3.6%)	2	1/7 (14.3%)	1
Insomnia	6/55 (10.9%)	6	7/56 (12.5%)	8	6/56 (10.7%)	6	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	4/55 (7.3%)	4	5/56 (8.9%)	5	2/56 (3.6%)	2	0/7 (0%)	0
Dyspnea	5/55 (9.1%)	5	7/56 (12.5%)	8	14/56 (25%)	16	1/7 (14.3%)	1
Vascular disorders
Hypertension	3/55 (5.5%)	3	3/56 (5.4%)	3	4/56 (7.1%)	5	1/7 (14.3%)	1
Hypotension	3/55 (5.5%)	3	6/56 (10.7%)	7	4/56 (7.1%)	5	1/7 (14.3%)	1

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

For this study, PIs are restricted from independently publishing results before completion of a single multicenter publication or one year after study completion, whichever occurs first. Baxter requires a review of the intended publication at least 60 days prior to submission. Baxter may request an additional delay of 45 days to secure patent and/or other proprietary protection.