Effectiveness of Stem Cell Treatment for Adults With Ischemic Cardiomyopathy (The FOCUS Study)

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Completed
• CT.gov ID: NCT00824005
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Cardiovascular Cell Therapy Research Network (CCTRN) (Other)
• Enrollment: 92
• Locations: 5
• Arms: 2
• Duration (Months): 38
• Patients Per Site: 18.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Coronary artery disease (CAD) is a common disorder that can lead to heart failure. Not all people with CAD are eligible for today's standard treatments. One new treatment approach uses stem cells-specialized cells capable of developing into other types of cells-to stimulate growth of new blood vessels for the heart. This study will determine the safety and effectiveness of withdrawing stem cells from someone's bone marrow and injecting those cells into the person's heart as a way of treating people with CAD and heart failure.

Condition or Disease	Intervention/Treatment	Phase
Chronic Ischemic Heart Disease; Left Ventricular Dysfunction; Angina; Ischemic Cardiomyopathy	Biological: Adult stem cells; Biological: Placebo	Phase 2

Detailed Description

Coronary artery disease (CAD), a disease in which blood vessels become clogged by a build-up of plaque, is the leading cause of heart failure, a condition in which the heart can no longer pump enough blood to the rest of the body. People with heart failure caused by CAD are said to have ischemic cardiomyopathy. Normal treatment for CAD involves coronary artery bypass grafting (in which a vein from another part of the body is grafted around an artery that has become blocked) or coronary angioplasty and stent placement (in which a blocked artery is opened and a small tube is placed to keep the artery open). However, some people with ischemic cardiomyopathy, such as those with substantial scar tissue on the heart wall or those with a particular heart structure, may not be eligible for these treatments. An alternative treatment being developed is therapeutic angiogenesis, which involves stimulating the growth of new blood vessels. Recent research has shown that withdrawing stem cells from bone marrow and implanting the cells into heart tissue may be an effective way to achieve therapeutic angiogenesis. This study will determine the safety and effectiveness of using stem cells to stimulate new blood vessel growth in the hearts of people with ischemic cardiomyopathy.

Participation in this study, including follow-up visits and phone calls, will last 60 months. Participants will first undergo 3 to 4 days of screening procedures that will include a physical examination, multiple lab tests, and a battery of tests on heart health. Next, participants will be randomized to receive either active stem cell injections or placebo injections. The injections and related procedures will be performed in a hospital and last approximately 72 hours. During this time, participants in both groups will first undergo a bone marrow aspiration procedure. Participants receiving active stem cells will also undergo NOGA electromechanical cardiac mapping, which involves inserting a monitoring device through a catheter and into the heart. Injections of stem cells will then be made to 15 damaged sites on the heart through a special catheter. Participants receiving placebo injections will receive 15 injections of an inactive, saline-based solution. After the injection procedures, all participants will undergo two echocardiograms, an electrocardiogram, blood tests, and overnight monitoring in a telemetry unit.

After the hospital stay, all participants will attend five study visits that will occur 1 week and 1, 3, 6, and 12 months after the injection procedures. At all study visits, participants will undergo an electrocardiogram, lab tests, and a review of adverse health events. On all but the last study visit, participants will have cardiac markers assessed, and they will wear a 24-hour Holter monitor to track heart activity. At the last three visits, participants will also complete quality of life questionnaires. All participants will then receive four follow-up telephone calls that will occur 2, 3, 4, and 5 years after the injection procedures.

Study Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Controlled, Phase II, Double-Blind Trial of Intramyocardial Injection of Autologous Bone Marrow Mononuclear Cells Under Electromechanical Guidance for Patients With Chronic Ischemic Heart Disease and Left Ventricular Dysfunction
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Injections Participants will receive placebo injections.	Biological: Placebo; Single procedure of intramyocardial electromechanical-guided needle insertions and injection of 5% human serum albumin and saline in 15 different injection sites; Other Names: Human serum albumin HSA
Experimental: Active Stem Cell Injections Participants will receive active stem cell injections.	Biological: Adult stem cells; Single procedure of intramyocardial electromechanical-guided injection of approximately 100 million bone marrow mononucleated cells (BM-MNCs), administered in 15 different injection sites; Other Names: Adult autologous stem cells Bone marrow mononucleated cells

Outcome Measures

Primary Outcome Measures

1. Change in Maximal Oxygen Consumption (VO2max) [Measured at Baseline and Month 6]

   The VO2(max) is assessed using the Naughton treadmill protocol.

2. Change in Left Ventricular End Systolic Volume (LVESV)as Assessed Via Echo [Measured at Baseline and Month 6]

   Echocardiographic measurements were performed by an echocardiographic core laboratory. LVESVs were calculated by the modified biplane Simpson method, using myocardial contrast to enhance endocardial definition. To account for patient body surface area, LVESV indices are reported.

3. Change in Reversible Defect Size [Measured at Baseline and Month 6]

   Adenosine myocardial perfusion (SPECT) tests were collected at baseline and 6 months to identify change in ischemic (reversible) defects. SPECT imaging was performed at rest and after adenosine infusion over 4 minutes. To enhance the detection of viability on resting images, sublingual nitroglycerin was administered 15 minutes before injecting technetium Tc 99m sestamibi for the resting image.

Secondary Outcome Measures

1. Regional Wall Motion by MRI (in Eligible Patients) [Measured at Baseline and Month 6]

   Regional wall motion as measured by cardiac MRI (in patients who are not contraindicated)

2. Regional Blood Flow Improvement by MRI (in Eligible Patients) [Measured at Baseline and Month 6]

   Regional blood flow improvement as measured by cardiac MRI (in patients who are not contraindicated)

3. Regional Wall Motion by Echocardiography [Measured at Baseline and Month 6]

   Movement of the left ventricular wall measured in mm from baseline to six months.

4. Clinical Improvement in CCS Classification (Angina Pectoris) [Measured at Baseline and Month 6]

   Clinical improvement in Canadian Cardiovascular Society (CCS) functional classification of angina pectoris. The CCS scale ranges from Class I (best)"able to conduct ordinary daily activity without causing angina" to Class IV (worst) "Inability to perform any physical activity without discomfort; anginal symptoms may be present at rest." Patients receive a rating of 1-4 for their anginal symptoms. Results reflect the mean change in the total score over time.

5. Clinical Improvement in NYHA Classification [Measured at Baseline and Month 6]

   Clinical improvement in New York Heart Association (NYHA) classification. The NYHA scale ranges from 1 (best)"Mild- no limitation of physical activity due to heart failure" to 4 (worst) "Severe-Unable to carry out any physical activity without discomfort due to heart failure". Patients receive a rating of 1-4 for their heart failure symptoms. Results reflect the mean change in the total score over time.

6. Number of Participants With a Decrease in Anti-anginal Medication [Measured at Baseline and Month 6]

   Number of participants with a decrease in anti-anginal medication (nitrates needed weekly)

7. Exercise Time and Level [Measured at Baseline and Month 6]

   Exercise time and level as assessed via six minute walk test. (change in number of feet walked)

8. Serum BNP Levels in Patients With CHF [Measured at Baseline and Month 6]

   Serum b-type natriuretic peptide (BNP) levels in patients with congestive heart failure (CHF). A minority number of patients had pro-BNP collected versus regular BNP; these numbers are reported in the analysis population description.

9. LV Diastolic Dimension [Measured at Baseline and Month 6]

   Left ventricular (LV) diastolic dimension as assessed by contrast echocardiography

10. Incidence of a Major Adverse Cardiac Event [Measured at Baseline and Month 6]

    Incidence of major adverse cardiac events (new MI, rehospitalization for PCI in coronary artery territories that were treated, death, or rehospitalization for acute coronary syndrome and for congestive heart failure). (Incidence rate)

11. Reduction in Fixed Perfusion Defect(s)Via SPECT [Measured at Baseline and Month 6]

    Fixed total defect is the stress total defect minus the reversible component.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients >18 years of age with significant coronary heart disease not amenable to revascularization.

• Left ventricular dysfunction (LVEF) less than or equal to 45%, measured by echocardiogram; limiting angina (Class II to IV); and/or congestive heart failure (CHF), NYHA class II to III

• Receiving maximal medical therapy, defined as a medical regimen that includes the maximal tolerated dose of at least two antiangina medications, such as beta-blockers, nitrates, or calcium-channel blockers

• Presence of a defect, as identified by single photon emission computed tomography (SPECT) isotope protocol, or viability, as identified by NOGA electromechanical cardiac mapping system

• Coronary artery disease not well suited to any other type of revascularization procedure in the target region of the ventricle, as determined by a cardiovascular surgeon and interventional cardiologist who are not investigators in the trial

• Hemodynamic stability, as defined by systolic blood pressure of at least 80 mm Hg without intravenous pressors or support devices

• Females of childbearing potential must be willing to use two forms of birth control for the duration of the study

Exclusion Criteria:

• Atrial fibrillation or flutter without a pacemaker that guarantees a stable heart rate

• Unstable angina

• Left ventricular (LV) thrombus, as documented by echocardiography or LV angiography

• A vascular anatomy that precludes cardiac catheterization

• Severe valvular disease or mechanical aortic valve that precludes safe entry of the catheter into the left ventricle

• Pregnant or lactating

• Platelet count less than 100,000 per mm3

• White blood cell count less than 2,000 per mm3

• Revascularization within 30 days of consent

• Transient ischemic attack or stroke within 60 days of study consent

• Implantable cardioverter-defibrillator shock within 30 days of baseline consent, and within 30 days of randomization

• Presence of ventricular tachycardia lasting 30 seconds or more on 24-hour Holter monitor or electrocardiogram (ECG) performed during screening period

• Bleeding diathesis, defined as an international normalized ratio of at least 2.0 in the absence of warfarin therapy

• A history of malignancy in the last 5 years excluding basal cell carcinoma, that has been surgically removed, with proof of surgical clean margins

• Has a known history of HIV, has active hepatitis B or active hepatitis C

• Any condition requiring immunosuppressive medication

• High-risk acute coronary syndrome (ACS) or a myocardial infarction in the month prior to consent

• A left ventricular wall thickness of <8 mm (by echocardiogram) of the infero-lateral wall at the target site for cell injection.

• Inability to walk on a treadmill, except for class IV angina patients, who will be evaluated separately

• Enrolled in an investigational device or drug study within the previous 30 days

• Hepatic dysfunction, as defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 1.5 times the upper limit of normal range prior to study entry

• Chronic renal insufficiency, defined as a serum creatinine level greater than 2.5 mg/dL or requiring dialysis

• Any other condition that in the judgment of the investigator would be a contraindication to enrollment or follow-up

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida-Department of Medicine	Gainesville	Florida	United States	32611
2	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota	United States	55407
3	Cleveland Clinic	Cleveland	Ohio	United States	44195
4	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
5	Texas Heart Institute	Houston	Texas	United States	77225

Sponsors and Collaborators

• The University of Texas Health Science Center, Houston
• National Heart, Lung, and Blood Institute (NHLBI)
• Cardiovascular Cell Therapy Research Network (CCTRN)

Investigators

• Study Chair: Robert Simari, MD, Cardiovascular Cell Therapy Research Network

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Click here for more information on the Cardiovascular Cell Therapy Research Network
• Click here for more information on the National Heart, Lung, and Blood Institute

Publications

• Gee AP, Richman S, Durett A, McKenna D, Traverse J, Henry T, Fisk D, Pepine C, Bloom J, Willerson J, Prater K, Zhao D, Koç JR, Ellis S, Taylor D, Cogle C, Moyé L, Simari R, Skarlatos S. Multicenter cell processing for cardiovascular regenerative medicine applications: the Cardiovascular Cell Therapy Research Network (CCTRN) experience. Cytotherapy. 2010 Sep;12(5):684-91. doi: 10.3109/14653249.2010.487900.
• Willerson JT, Perin EC, Ellis SG, Pepine CJ, Henry TD, Zhao DX, Lai D, Penn MS, Byrne BJ, Silva G, Gee A, Traverse JH, Hatzopoulos AK, Forder JR, Martin D, Kronenberg M, Taylor DA, Cogle CR, Baraniuk S, Westbrook L, Sayre SL, Vojvodic RW, Gordon DJ, Skarlatos SI, Moyé LA, Simari RD; Cardiovascular Cell Therapy Research Network (CCTRN). Intramyocardial injection of autologous bone marrow mononuclear cells for patients with chronic ischemic heart disease and left ventricular dysfunction (First Mononuclear Cells injected in the US [FOCUS]): Rationale and design. Am Heart J. 2010 Aug;160(2):215-23. doi: 10.1016/j.ahj.2010.03.029.
• Zierold C, Carlson MA, Obodo UC, Wise E, Piazza VA, Meeks MW, Vojvodic RW, Baraniuk S, Henry TD, Gee AP, Ellis SG, Moyé LA, Pepine CJ, Cogle CR, Taylor DA. Developing mechanistic insights into cardiovascular cell therapy: Cardiovascular Cell Therapy Research Network Biorepository Core Laboratory rationale. Am Heart J. 2011 Dec;162(6):973-80. doi: 10.1016/j.ahj.2011.05.024.

• Responsible Party: Dr Lemuel A Moye III, Professor - School of Public Health, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT00824005
• Other Study ID Numbers: 580; U01HL087318; 1 U01-HL-087318-01 (Project 3)
• First Posted: Jan 16, 2009
• Last Update Posted: Jul 1, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by Dr Lemuel A Moye III, Professor - School of Public Health, The University of Texas Health Science Center, Houston: Congestive Heart Failure; Regional Wall Motion; Perfusion Defects
• Additional relevant MeSH terms: Heart Diseases; Cardiomyopathies; Myocardial Ischemia; Coronary Artery Disease; Ventricular Dysfunction; Ventricular Dysfunction, Left; Ischemia

Study Results

Participant Flow

Recruitment Details	Enrollment took place at five Network centers and their associated satellite facilities between April 29, 2009 and April 18, 2011. The main centers are located in Ohio, Texas, Florida, Minnesota, and Tennessee. Study brochures, patient informational DVDs, and clinical trials.gov were among the tools used for recruitment.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants will receive placebo injections.	Participants will receive active stem cell injections.
Period Title: Overall Study
STARTED	31	61
COMPLETED	31	59
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Placebo Injections	Active Stem Cell Injections	Total
Arm/Group Description	Participants will receive placebo injections.	Participants will receive active stem cell injections.	Total of all reporting groups
Overall Participants	31	61	92
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.32 (8.25)	63.95 (10.90)	63.4 (10.1)
Sex: Female, Male (Count of Participants)
Female	2 6.5%	8 13.1%	10 10.9%
Male	29 93.5%	53 86.9%	82 89.1%
Region of Enrollment (participants) [Number]
United States	31 100%	61 100%	92 100%

Outcome Measures

1. Primary Outcome

Title	Change in Maximal Oxygen Consumption (VO2max)
Description	The VO2(max) is assessed using the Naughton treadmill protocol.
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Only participants with both baseline and 6 month VO2max data available are included.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	27	52
Mean (Standard Deviation) [mL/kg/min]	-0.6 (3.2)	0.4 (2.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Injections, Active Stem Cell Injections
	Comments	Compare the change in the cell group to the change in the placebo group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.169
	Comments	No adjustment for multiple comparisons
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -0.42 to 2.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.9
	Estimation Comments

2. Primary Outcome

Title	Change in Left Ventricular End Systolic Volume (LVESV)as Assessed Via Echo
Description	Echocardiographic measurements were performed by an echocardiographic core laboratory. LVESVs were calculated by the modified biplane Simpson method, using myocardial contrast to enhance endocardial definition. To account for patient body surface area, LVESV indices are reported.
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Only participants with both baseline and six month LVESV data available are included.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	28	54
Mean (Standard Deviation) [mL/m2]	0 (10.8)	-0.9 (11.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Injections, Active Stem Cell Injections
	Comments	Change in the difference of end systolic volume over time.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.856
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; -10.05 to 12.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 23.9
	Estimation Comments

3. Primary Outcome

Title	Change in Reversible Defect Size
Description	Adenosine myocardial perfusion (SPECT) tests were collected at baseline and 6 months to identify change in ischemic (reversible) defects. SPECT imaging was performed at rest and after adenosine infusion over 4 minutes. To enhance the detection of viability on resting images, sublingual nitroglycerin was administered 15 minutes before injecting technetium Tc 99m sestamibi for the resting image.
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Only participants with both baseline and six month reversible defect data available are included.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	26	50
Mean (Standard Deviation) [percentage of reversible defect]	-2.7 (18.2)	-3.9 (25.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Injections, Active Stem Cell Injections
	Comments	Change in percent of the defect that is reversible
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.835
	Comments	Is the change in percent reversible defect the same between the two groups
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -12.5 to 10.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 22.3
	Estimation Comments

4. Secondary Outcome

Title	Regional Wall Motion by MRI (in Eligible Patients)
Description	Regional wall motion as measured by cardiac MRI (in patients who are not contraindicated)
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

The small number of patients without contraindications for MRI (n=17) precluded performing informative analysis on the MRI data.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	0	0

5. Secondary Outcome

Title	Regional Blood Flow Improvement by MRI (in Eligible Patients)
Description	Regional blood flow improvement as measured by cardiac MRI (in patients who are not contraindicated)
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

The small number of patients without contraindications for MRI (n=17) precluded performing informative analysis on the MRI data.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	0	0

6. Secondary Outcome

Title	Regional Wall Motion by Echocardiography
Description	Movement of the left ventricular wall measured in mm from baseline to six months.
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Only participants with both baseline and six month wall motion data available are included.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	26	55
Mean (Standard Deviation) [mm]	0 (0.4)	0 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Injections, Active Stem Cell Injections
	Comments	Difference in the change between the two groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.471
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.5
	Estimation Comments

7. Secondary Outcome

Title	Clinical Improvement in CCS Classification (Angina Pectoris)
Description	Clinical improvement in Canadian Cardiovascular Society (CCS) functional classification of angina pectoris. The CCS scale ranges from Class I (best)"able to conduct ordinary daily activity without causing angina" to Class IV (worst) "Inability to perform any physical activity without discomfort; anginal symptoms may be present at rest." Patients receive a rating of 1-4 for their anginal symptoms. Results reflect the mean change in the total score over time.
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Only participants with both baseline and six month CCS data available are included.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	22	44
Mean (Standard Deviation) [units on a scale]	-0.3 (0.7)	-0.5 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Injections, Active Stem Cell Injections
	Comments	Change in average improvement in Canadian Class Score over time between the two groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.227
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.66 to 0.16
	Parameter Dispersion	Type: Standard Deviation; Value: 0.784
	Estimation Comments

8. Secondary Outcome

Title	Clinical Improvement in NYHA Classification
Description	Clinical improvement in New York Heart Association (NYHA) classification. The NYHA scale ranges from 1 (best)"Mild- no limitation of physical activity due to heart failure" to 4 (worst) "Severe-Unable to carry out any physical activity without discomfort due to heart failure". Patients receive a rating of 1-4 for their heart failure symptoms. Results reflect the mean change in the total score over time.
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Only participants with both baseline and six month NYHA class data available are included.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	30	55
Mean (Standard Deviation) [units on a scale]	-0.1 (0.7)	-0.3 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Injections, Active Stem Cell Injections
	Comments	Difference in the change in NYHA score between the two groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.361
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.176
	Confidence Interval	(2-Sided) 95%; -0.56 to 0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.845
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants With a Decrease in Anti-anginal Medication
Description	Number of participants with a decrease in anti-anginal medication (nitrates needed weekly)
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Only participants with both baseline and six month anti-anginal medication data available are included.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	28	50
Number [participants]	0 0%	2 3.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Injections, Active Stem Cell Injections
	Comments	Difference in the change in anti-anginal meds across groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Difference in the proportion of particip
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.09
	Parameter Dispersion	Type: Standard Deviation; Value: 0.045
	Estimation Comments

10. Secondary Outcome

Title	Exercise Time and Level
Description	Exercise time and level as assessed via six minute walk test. (change in number of feet walked)
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Only participants with both baseline and six month 6 minute walk data available are included.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	29	51
Mean (Standard Deviation) [feet]	80 (415)	184 (407)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Injections, Active Stem Cell Injections
	Comments	Change in six minute walk distance
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.302
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	104
	Confidence Interval	(2-Sided) 95%; -95 to 303
	Parameter Dispersion	Type: Standard Deviation; Value: 409
	Estimation Comments

11. Secondary Outcome

Title	Serum BNP Levels in Patients With CHF
Description	Serum b-type natriuretic peptide (BNP) levels in patients with congestive heart failure (CHF). A minority number of patients had pro-BNP collected versus regular BNP; these numbers are reported in the analysis population description.
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Only participants with both baseline and six month BNP data available are included.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	20	30
BNP	63 (249)	28 (117)
pro-BNP	234 (1636)	497 (1637)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Injections, Active Stem Cell Injections
	Comments	Difference in the change in BNP(reg) between cell and placebo group
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-34.7
	Confidence Interval	(2-Sided) 95%; -150 to 80
	Parameter Dispersion	Type: Standard Deviation; Value: 176
	Estimation Comments

12. Secondary Outcome

Title	LV Diastolic Dimension
Description	Left ventricular (LV) diastolic dimension as assessed by contrast echocardiography
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Only participants with both baseline and six month LV diastolic data available are included.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	28	54
Mean (Standard Deviation) [mL]	-8.5 (34)	0.9 (30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Injections, Active Stem Cell Injections
	Comments	Change in the difference of end diastolic volume between the two groups over time.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.198
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	9.5
	Confidence Interval	(2-Sided) 95%; -5.03 to 23.93
	Parameter Dispersion	Type: Standard Deviation; Value: 31.2
	Estimation Comments

13. Secondary Outcome

Title	Incidence of a Major Adverse Cardiac Event
Description	Incidence of major adverse cardiac events (new MI, rehospitalization for PCI in coronary artery territories that were treated, death, or rehospitalization for acute coronary syndrome and for congestive heart failure). (Incidence rate)
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Incidence of major adverse cardiac events between baseline and 6 months. (Incidence rate)

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	31	61
Number [events]	4	5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Injections, Active Stem Cell Injections
	Comments	The difference in the incidence of major adverse cardiac events between the two groups over time. (Incidence rate)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.47
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Difference in the incidence rates
	Estimated Value	-0.047
	Confidence Interval	(2-Sided) 95%; -0.133 to 0.039
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.044
	Estimation Comments

14. Secondary Outcome

Title	Reduction in Fixed Perfusion Defect(s)Via SPECT
Description	Fixed total defect is the stress total defect minus the reversible component.
Time Frame	Measured at Baseline and Month 6

Outcome Measure Data

Analysis Population Description

Only participants with both baseline and six month fixed defect data available are included.

Arm/Group Title	Placebo Injections	Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.	Participants received active stem cell injections.
Measure Participants	25	52
Mean (Standard Deviation) [percentage of defect that is fixed]	1.9 (7.7)	1.2 (8.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Injections, Active Stem Cell Injections
	Comments	Difference in the change between the two groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -4.78 to 3.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 8.4
	Estimation Comments

Adverse Events

Time Frame	Events reported are from Randomization Date to the 6 month endpoint data collection window (i.e. 210 days post intervention)
Arm/Group Title	Placebo Injections		Active Stem Cell Injections
Arm/Group Description	Participants received placebo injections.		Participants received active stem cell injections.
All Cause Mortality
	Placebo Injections		Active Stem Cell Injections
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo Injections		Active Stem Cell Injections
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/31 (19.4%)		9/61 (14.8%)
Cardiac disorders
Chest pain	2/31 (6.5%)	3	4/61 (6.6%)	4
Tachycardia	1/31 (3.2%)	1	3/61 (4.9%)	7
Heart Failure	3/31 (9.7%)	5	2/61 (3.3%)	5
Other (Not Including Serious) Adverse Events
	Placebo Injections		Active Stem Cell Injections
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/31 (35.5%)		19/61 (31.1%)
Blood and lymphatic system disorders
Anemia	0/31 (0%)	0	3/61 (4.9%)	4
Cardiac disorders
Tachycardia	3/31 (9.7%)	3	3/61 (4.9%)	5
Change in BNP levels	3/31 (9.7%)	3	8/61 (13.1%)	8
Gastrointestinal disorders
Nausea	2/31 (6.5%)	4	2/61 (3.3%)	3
Respiratory, thoracic and mediastinal disorders
Shortness of breath	3/31 (9.7%)	3	3/61 (4.9%)	3

Limitations/Caveats

Sample size was small and required large improvements in order to show significant treatment effects. SPECT often underestimates reversibility and viability in those with multivessel disease. Presence of cardiac devices limited MRI evaluation.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.