Myocardial Ischemia
Conditions
Keywords
angina
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.
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.
Interventions
BIOLOGICALCLBS14 (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.
BIOLOGICALCLBS14 (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.
BIOLOGICALplacebo 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.
Sponsors
Lisata Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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. |
| 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. |
| 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 |
Countries
United States
Participant flow
Recruitment details
Enrollment was conducted at 26 clinical sites in the US.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| CLBS14: Low-Dose Group Intramyocardial injections of auto-CD34+ cells at low dose (1 x 10\^5 cells/kg bodyweight) | 55 |
| CLBS14: High-Dose Group Intramyocardial injections of auto-CD34+ cells at high dose (5 x 10\^5 cells/kg bodyweight) | 56 |
| Placebo Control Intramyocardial placebo injections | 56 |
| Total | 167 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Patient/Caregiver Preference | 2 | 2 | 3 |
Baseline characteristics
| Characteristic | CLBS14: Low-Dose Group | CLBS14: High-Dose Group | Placebo Control | Total |
|---|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 9.1 | 59.8 years STANDARD_DEVIATION 9.2 | 61.8 years STANDARD_DEVIATION 8.5 | 61.0 years STANDARD_DEVIATION 8.9 |
| Region of Enrollment United States | 55 participants | 56 participants | 56 participants | 167 participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 6 Participants | 22 Participants |
| Sex: Female, Male Male | 46 Participants | 49 Participants | 50 Participants | 145 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 56 | 3 / 56 | 0 / 7 |
| other Total, other adverse events | 54 / 55 | 52 / 56 | 52 / 56 | 5 / 7 |
| serious Total, serious adverse events | 21 / 55 | 24 / 56 | 32 / 56 | 5 / 7 |
Outcome results
Primary
Number of Angina Episodes Per Week at 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.
Time frame: 6 and 12 months
Population: Intent-to-treat (ITT) population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CLBS14: Low-Dose Group | Number of Angina Episodes Per Week at 6 and 12 Months | 6 months | 6.8 angina episodes/week | Standard Deviation 1.1 |
| CLBS14: Low-Dose Group | Number of Angina Episodes Per Week at 6 and 12 Months | 12 months | 6.3 angina episodes/week | Standard Deviation 1.2 |
| CLBS14: High-Dose Group | Number of Angina Episodes Per Week at 6 and 12 Months | 6 months | 8.3 angina episodes/week | Standard Deviation 1.1 |
| CLBS14: High-Dose Group | Number of Angina Episodes Per Week at 6 and 12 Months | 12 months | 7.2 angina episodes/week | Standard Deviation 1.1 |
| Placebo Control | Number of Angina Episodes Per Week at 6 and 12 Months | 6 months | 10.9 angina episodes/week | Standard Deviation 1.2 |
| Placebo Control | Number of Angina Episodes Per Week at 6 and 12 Months | 12 months | 11.0 angina episodes/week | Standard Deviation 1.2 |
Comparison: Frequency of angina episodes per week 6 months after treatment.p-value: 0.02ANCOVA
Comparison: Frequency of angina episodes per week 12 months after treatment.p-value: 0.035ANCOVA
Comparison: Frequency of angina episodes per week 6 months after treatment.p-value: 0.167ANCOVA
Comparison: Frequency of angina episodes per week 12 months after treatment.p-value: 0.181ANCOVA
Secondary
Change in Anti-anginal Medication (ie, Nitroglycerin) Use
The mean nitroglycerin use per week was analyzed at baseline and 6 months
Time frame: Baseline to 6 months
Population: ITT population (note that the number of participants analyzed may differ due to missing data)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CLBS14: Low-Dose Group | Change in Anti-anginal Medication (ie, Nitroglycerin) Use | -6.3 nitroglycerin use (tablets per week) | Standard Deviation 8.1 |
| CLBS14: High-Dose Group | Change in Anti-anginal Medication (ie, Nitroglycerin) Use | -7.3 nitroglycerin use (tablets per week) | Standard Deviation 9.9 |
| Placebo Control | Change in Anti-anginal Medication (ie, Nitroglycerin) Use | -4.2 nitroglycerin use (tablets per week) | Standard Deviation 8.8 |
Secondary
Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months
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
Population: ITT population (note that the number of participants analyzed may differ due to missing data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CLBS14: Low-Dose Group | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Treatment satisfaction scale | 11.4 score on a scale | Standard Deviation 19.5 |
| CLBS14: Low-Dose Group | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Angina frequency scale | 28.3 score on a scale | Standard Deviation 25.3 |
| CLBS14: Low-Dose Group | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Physical limitations scale | 12.4 score on a scale | Standard Deviation 15.6 |
| CLBS14: Low-Dose Group | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Angina stability scale | 29.8 score on a scale | Standard Deviation 30.1 |
| CLBS14: Low-Dose Group | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Disease perception scale | 14.4 score on a scale | Standard Deviation 23.2 |
| CLBS14: High-Dose Group | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Angina frequency scale | 21.7 score on a scale | Standard Deviation 24.6 |
| CLBS14: High-Dose Group | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Physical limitations scale | 10.5 score on a scale | Standard Deviation 17.1 |
| CLBS14: High-Dose Group | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Angina stability scale | 25.5 score on a scale | Standard Deviation 30.3 |
| CLBS14: High-Dose Group | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Treatment satisfaction scale | 10.3 score on a scale | Standard Deviation 21.8 |
| CLBS14: High-Dose Group | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Disease perception scale | 12.0 score on a scale | Standard Deviation 19.4 |
| Placebo Control | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Disease perception scale | 15.1 score on a scale | Standard Deviation 21.1 |
| Placebo Control | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Treatment satisfaction scale | 4.9 score on a scale | Standard Deviation 19 |
| Placebo Control | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Physical limitations scale | 10.7 score on a scale | Standard Deviation 15.2 |
| Placebo Control | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Angina frequency scale | 26.0 score on a scale | Standard Deviation 24.3 |
| Placebo Control | Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months | Angina stability scale | 13.8 score on a scale | Standard Deviation 31.9 |
Secondary
Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters
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
Population: ITT population (note that the number of participants analyzed may differ due to missing data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CLBS14: Low-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | General health | 7.6 score on a scale | Standard Deviation 15.5 |
| CLBS14: Low-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Health transition | 40.4 score on a scale | Standard Deviation 32.5 |
| CLBS14: Low-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Social functioning | 16.8 score on a scale | Standard Deviation 24.1 |
| CLBS14: Low-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Vitality | 14.6 score on a scale | Standard Deviation 18 |
| CLBS14: Low-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Physical functioning | 13.7 score on a scale | Standard Deviation 18.1 |
| CLBS14: Low-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Mental health | 6.2 score on a scale | Standard Deviation 16 |
| CLBS14: Low-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Bodily pain | 13.5 score on a scale | Standard Deviation 22.1 |
| CLBS14: Low-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Role-physical | 17.5 score on a scale | Standard Deviation 35.1 |
| CLBS14: Low-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Role emotional | 10.7 score on a scale | Standard Deviation 43.9 |
| CLBS14: High-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Vitality | 14.0 score on a scale | Standard Deviation 20.7 |
| CLBS14: High-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Physical functioning | 13.2 score on a scale | Standard Deviation 18.4 |
| CLBS14: High-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Role-physical | 15.9 score on a scale | Standard Deviation 33.6 |
| CLBS14: High-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Bodily pain | 13.5 score on a scale | Standard Deviation 21.6 |
| CLBS14: High-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | General health | 6.0 score on a scale | Standard Deviation 15.3 |
| CLBS14: High-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Social functioning | 12.2 score on a scale | Standard Deviation 24.3 |
| CLBS14: High-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Role emotional | 17.9 score on a scale | Standard Deviation 51.8 |
| CLBS14: High-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Mental health | 8.4 score on a scale | Standard Deviation 17.9 |
| CLBS14: High-Dose Group | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Health transition | 32.7 score on a scale | Standard Deviation 31.1 |
| Placebo Control | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Bodily pain | 9.4 score on a scale | Standard Deviation 25.1 |
| Placebo Control | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Physical functioning | 7.9 score on a scale | Standard Deviation 21.8 |
| Placebo Control | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Role emotional | 9.7 score on a scale | Standard Deviation 50.5 |
| Placebo Control | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Role-physical | 19.4 score on a scale | Standard Deviation 33.2 |
| Placebo Control | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Health transition | 29.6 score on a scale | Standard Deviation 30 |
| Placebo Control | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Vitality | 8.9 score on a scale | Standard Deviation 23.2 |
| Placebo Control | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | General health | 6.3 score on a scale | Standard Deviation 15.4 |
| Placebo Control | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Mental health | 3.6 score on a scale | Standard Deviation 13.6 |
| Placebo Control | Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters | Social functioning | 12.0 score on a scale | Standard Deviation 32.3 |
Secondary
Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise
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
Population: ITT population (note that the number of participants analyzed may differ due to missing data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CLBS14: Low-Dose Group | Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise | Change from baseline to 6 months | 139 seconds | Standard Deviation 151 |
| CLBS14: Low-Dose Group | Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise | Change from baseline to 12 months | 140 seconds | Standard Deviation 171 |
| CLBS14: High-Dose Group | Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise | Change from baseline to 6 months | 110 seconds | Standard Deviation 155 |
| CLBS14: High-Dose Group | Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise | Change from baseline to 12 months | 103 seconds | Standard Deviation 162 |
| Placebo Control | Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise | Change from baseline to 6 months | 69 seconds | Standard Deviation 122 |
| Placebo Control | Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise | Change from baseline to 12 months | 58 seconds | Standard Deviation 146 |
Comparison: Change from baseline to 6 monthsp-value: 0.014ANCOVA
Comparison: Change from baseline to 12 monthsp-value: 0.017ANCOVA
Comparison: Change from baseline to 6 monthsp-value: 0.097ANCOVA
Comparison: Change from baseline to 12 monthsp-value: 0.134ANCOVA
Secondary
Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels
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
Population: ITT population (note that the number of participants analyzed may differ due to missing data)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CLBS14: Low-Dose Group | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | Worsening by 1 level (CCS) from baseline | 2 Participants |
| CLBS14: Low-Dose Group | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | Improvement by 2 levels (CCS) from baseline | 11 Participants |
| CLBS14: Low-Dose Group | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | No change in CCS classification from baseline | 16 Participants |
| CLBS14: Low-Dose Group | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | Improvement by 1 level (CCS) from baseline | 22 Participants |
| CLBS14: Low-Dose Group | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | Worsening by 2 levels (CCS) from baseline | 0 Participants |
| CLBS14: High-Dose Group | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | Improvement by 2 levels (CCS) from baseline | 12 Participants |
| CLBS14: High-Dose Group | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | No change in CCS classification from baseline | 19 Participants |
| CLBS14: High-Dose Group | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | Improvement by 1 level (CCS) from baseline | 17 Participants |
| CLBS14: High-Dose Group | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | Worsening by 1 level (CCS) from baseline | 3 Participants |
| CLBS14: High-Dose Group | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | Worsening by 2 levels (CCS) from baseline | 0 Participants |
| Placebo Control | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | Worsening by 2 levels (CCS) from baseline | 0 Participants |
| Placebo Control | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | Worsening by 1 level (CCS) from baseline | 4 Participants |
| Placebo Control | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | No change in CCS classification from baseline | 16 Participants |
| Placebo Control | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | Improvement by 2 levels (CCS) from baseline | 5 Participants |
| Placebo Control | Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels | Improvement by 1 level (CCS) from baseline | 19 Participants |