Trial Outcomes & Findings for Safety and Efficacy of Autologous Bone Marrow Mononuclear Cells in Patients With Severe Critical Limb Ischemia (NCT NCT01472289)
NCT ID: NCT01472289
Last Updated: 2015-11-18
Results Overview
The Primary objective of this study was to determine the safety of intramuscular administration of concentrated autologous BMMNCs harvested, and processed using the Res-Q 60 technology (a point-of-care system). Safety measurements included close vigilance for major limb amputation free survival at 1, 3, 6 and 12 months post BMMNCs administration and stringent reporting of AEs and SAEs.
COMPLETED
PHASE1/PHASE2
17 participants
1, 3, 6 and 12 Months
2015-11-18
Participant Flow
Participant milestones
| Measure |
BMMNC Treated Group
All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells (BMMNCs) concentrate prepared using the Res-Q 60 technology (a point of care system) and injected the concentrate intra-muscularly into multiple sites in the ischemic tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc.
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Overall Study
STARTED
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17
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Overall Study
COMPLETED
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15
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Overall Study
NOT COMPLETED
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2
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Reasons for withdrawal
| Measure |
BMMNC Treated Group
All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells (BMMNCs) concentrate prepared using the Res-Q 60 technology (a point of care system) and injected the concentrate intra-muscularly into multiple sites in the ischemic tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc.
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|---|---|
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Overall Study
Death
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2
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Baseline Characteristics
Safety and Efficacy of Autologous Bone Marrow Mononuclear Cells in Patients With Severe Critical Limb Ischemia
Baseline characteristics by cohort
| Measure |
BMMNC Treated Group
n=17 Participants
All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) and injected intra-muscularly into multiple sites in the ischemic muscle of the affected limb at 0.5 cc/injection for a total of 15-20 cc.
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Age, Continuous
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48.8 years
STANDARD_DEVIATION 13.07 • n=5 Participants
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Sex: Female, Male
Female
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2 Participants
n=5 Participants
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Sex: Female, Male
Male
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15 Participants
n=5 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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17 Participants
n=5 Participants
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
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Race (NIH/OMB)
White
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0 Participants
n=5 Participants
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Region of Enrollment
India
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17 participants
n=5 Participants
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PRIMARY outcome
Timeframe: 1, 3, 6 and 12 MonthsPopulation: All the safety end points in the study were analyzed on the ITT population. Out of 17 subjects, adverse events were reported for seven subjects. Of the seven subjects, three underwent major amputation, two reported minor amputation, and two died due to cardiac arrest (unrelated death). Furthermore, major limb amputation free survival rate was 14.
The Primary objective of this study was to determine the safety of intramuscular administration of concentrated autologous BMMNCs harvested, and processed using the Res-Q 60 technology (a point-of-care system). Safety measurements included close vigilance for major limb amputation free survival at 1, 3, 6 and 12 months post BMMNCs administration and stringent reporting of AEs and SAEs.
Outcome measures
| Measure |
BMMNC Treated Group
n=17 Participants
All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) and injected intra-muscularly into multiple sites in the ischemic tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc.
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Number of Participants With Adverse Events as a Measure of Safety and Major Limb Amputation Free Survival Post BMMNC Administration
Major Limb Amputation Free Survival Rate
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14 participants
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Number of Participants With Adverse Events as a Measure of Safety and Major Limb Amputation Free Survival Post BMMNC Administration
Major Amputation
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3 participants
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Number of Participants With Adverse Events as a Measure of Safety and Major Limb Amputation Free Survival Post BMMNC Administration
Minor Amputation
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2 participants
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Number of Participants With Adverse Events as a Measure of Safety and Major Limb Amputation Free Survival Post BMMNC Administration
Unrelated Death
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2 participants
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Number of Participants With Adverse Events as a Measure of Safety and Major Limb Amputation Free Survival Post BMMNC Administration
Total Adverse Events
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7 participants
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SECONDARY outcome
Timeframe: Baseline and 12 monthPopulation: Efficacy measures were established by assessing CLI symptoms known to be reliable and valid. The efficacy endpoints were analyzed on per protocol (PP) basis (N=14).
Measurement of blood supply facilitated by the formation of collateral blood vessels assessed by CT angiography after the procedure.
Outcome measures
| Measure |
BMMNC Treated Group
n=14 Participants
All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) and injected intra-muscularly into multiple sites in the ischemic tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc.
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Degree of Angiogenesis Measured by the Number of Collateral Blood Vessels Formed at 12 Months
Number of Collateral vessels at Baseline
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2.42 Number of Vessels
Standard Deviation 0.775
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Degree of Angiogenesis Measured by the Number of Collateral Blood Vessels Formed at 12 Months
Number of Collateral vessels at 12 months
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5.59 Number of Vessels
Standard Deviation 1.146
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SECONDARY outcome
Timeframe: Baseline, 1, 3, 6 and 12 monthsPopulation: Efficacy measures were established by assessing CLI symptoms known to be reliable and valid. The efficacy endpoints were analyzed on per protocol (PP) basis (N=14).
ABI was used to provide a measure of blood flow in the lower limbs. It is the ratio of the blood pressure in the lower limbs to the blood pressure in the upper limbs. Compared to the upper limb, lower blood pressure in the lower limb is an indication of blocked arteries (peripheral vascular disease). The ABI was calculated by dividing the systolic blood pressure at the ankle by the systolic blood pressures in the arm. ABI test was performed at baseline, 1 month, 3 months, 6 months, and 12 months.
Outcome measures
| Measure |
BMMNC Treated Group
n=14 Participants
All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) and injected intra-muscularly into multiple sites in the ischemic tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc.
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Measurement of Mean Change in Ankle Brachial Index From Baseline to 12 Months
ABI at Baseline
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0.507 Ratio
Standard Deviation 0.0971
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Measurement of Mean Change in Ankle Brachial Index From Baseline to 12 Months
ABI at 1 Month
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0.612 Ratio
Standard Deviation 0.1653
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Measurement of Mean Change in Ankle Brachial Index From Baseline to 12 Months
ABI at 3 Months
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0.819 Ratio
Standard Deviation 0.2829
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Measurement of Mean Change in Ankle Brachial Index From Baseline to 12 Months
ABI at 6 Months
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0.879 Ratio
Standard Deviation 0.2467
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Measurement of Mean Change in Ankle Brachial Index From Baseline to 12 Months
ABI at 12 Months
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0.696 Ratio
Standard Deviation 0.2650
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SECONDARY outcome
Timeframe: Baseline, 1, 3, 6 and 12 monthsPopulation: The efficacy endpoints were analyzed on per protocol (PP) basis (N=14).
TcPO2 was used to assess the partial pressure (tension) of oxygen in the capillaries of tissues of lower limbs. It was measured by applying a special set of electrodes to the skin. These electrodes contain photoelectric sensors capable of detecting the specific wavelengths of radiation emitted by oxygenated versus reduced hemoglobin.
Outcome measures
| Measure |
BMMNC Treated Group
n=14 Participants
All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) and injected intra-muscularly into multiple sites in the ischemic tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc.
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|---|---|
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Measurement of Change in Transcutaneous Oxygen Pressure (TcPO2) From Baseline to 12 Months
TcPO2 at Baseline
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14.66 mmHg
Standard Deviation 6.925
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Measurement of Change in Transcutaneous Oxygen Pressure (TcPO2) From Baseline to 12 Months
TcPO2 at 1 Month
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25.10 mmHg
Standard Deviation 11.906
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Measurement of Change in Transcutaneous Oxygen Pressure (TcPO2) From Baseline to 12 Months
TcPO2 at 3 Months
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36.85 mmHg
Standard Deviation 17.892
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Measurement of Change in Transcutaneous Oxygen Pressure (TcPO2) From Baseline to 12 Months
TcPO2 at 6 Months
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34.58 mmHg
Standard Deviation 15.500
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Measurement of Change in Transcutaneous Oxygen Pressure (TcPO2) From Baseline to 12 Months
TcPO2 at 12 Months
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35.75 mmHg
Standard Deviation 17.035
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SECONDARY outcome
Timeframe: Baseline, 1, 3, 6 and 12 monthsPopulation: Efficacy measures were established by assessing CLI symptoms known to be reliable and valid. The efficacy endpoints were analyzed on per protocol (PP) basis (N=14).
Rest pain is a burning sensation felt at rest, usually in the skin of the foot. It is a symptom of critical ischemia due to severe, chronic, and occlusive peripheral arterial disease (PAD). While, Intermittent Claudication is a crampy leg pain that occurs during exercise, especially walking. The pain is due to the insufficient blood flow in the legs (caused by blocked arteries). Intermittent claudication is the most prominent symptom of PAD. Both Rest Pain assessment and Intermittent Claudication assessment was performed through Visual Analog Scale or Visual Analogue Scale (VAS). VAS is a psychometric (self-report) response scale that ranges from 0 to 10, where a mark of zero indicates no pain and a mark of 10 indicates worst possible pain.
Outcome measures
| Measure |
BMMNC Treated Group
n=14 Participants
All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) and injected intra-muscularly into multiple sites in the ischemic tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc.
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Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months
Rest Pain Score at Baseline
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2.80 scores on a scale
Standard Deviation 0.80
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Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months
Rest Pain Score at 1 Month
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1.2 scores on a scale
Standard Deviation 1.17
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Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months
Rest Pain Score at 3 Months
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0.6 scores on a scale
Standard Deviation 0.87
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Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months
Rest Pain Score at 6 Months
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0.4 scores on a scale
Standard Deviation 0.90
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Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months
Rest Pain Score at 12 Months
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0.0 scores on a scale
Standard Deviation 0.00
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Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months
Intermittent Claudication Pain Score at Baseline
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7.80 scores on a scale
Standard Deviation 0.97
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Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months
Intermittent Claudication Pain Score at 1 Month
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4.9 scores on a scale
Standard Deviation 2.22
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Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months
Intermittent Claudication Pain Score at 3 Months
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2.8 scores on a scale
Standard Deviation 2.61
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Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months
Intermittent Claudication Pain Score at 6 Months
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1.1 scores on a scale
Standard Deviation 1.44
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Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months
Intermittent Claudication Pain Score at 12 Months
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0.2 scores on a scale
Standard Deviation 0.58
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SECONDARY outcome
Timeframe: Baseline, 1, 3, 6 and 12 monthsPopulation: Efficacy measures were established by assessing CLI symptoms known to be reliable and valid. The efficacy endpoints were analyzed on per protocol (PP) basis (N=14).
Evaluation of the integument for ulceration, gangrene and other skin changes in the affected limb was performed at baseline and follow-up visits at 1 month, 3 months, 6 months, and 12 months.The ulceration and gangrene in the affected limb of the subjects was evaluated by visual clinical inspection.
Outcome measures
| Measure |
BMMNC Treated Group
n=14 Participants
All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) and injected intra-muscularly into multiple sites in the ischemic tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc.
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Clinical Evaluation for the Presence of Ulcer and/or Gangrene in the Affected Limb From Baseline to 12 Months
Ulcer and/ or Gangrene present at 12 Months
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0 Participants
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Clinical Evaluation for the Presence of Ulcer and/or Gangrene in the Affected Limb From Baseline to 12 Months
Ulcer and/ or Gangrene present at Baseline
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11 Participants
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Clinical Evaluation for the Presence of Ulcer and/or Gangrene in the Affected Limb From Baseline to 12 Months
Ulcer and/or Gangrene present at 1 Month
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10 Participants
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Clinical Evaluation for the Presence of Ulcer and/or Gangrene in the Affected Limb From Baseline to 12 Months
Ulcer and/or Gangrene present at 3 Months
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6 Participants
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Clinical Evaluation for the Presence of Ulcer and/or Gangrene in the Affected Limb From Baseline to 12 Months
Ulcer and/or Gangrene present at 6 Months
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2 Participants
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SECONDARY outcome
Timeframe: Baseline, 1, 3, 6 and 12 monthsPopulation: Efficacy measures were established by assessing CLI symptoms known to be reliable and valid. The efficacy endpoints were analyzed on per protocol (PP) basis (N=14).
Subjects were analyzed to see if they were able to walk any distance and the distance covered by patients in 6 minutes was measured to assess the functional changes from baseline. The American Thoracic Society has issued guidelines for the 6-minute walk test (6 MWT). The 6 MWT is safe, easy to administer, well tolerated, and reflects activities of daily living.
Outcome measures
| Measure |
BMMNC Treated Group
n=14 Participants
All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) and injected intra-muscularly into multiple sites in the ischemic tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc.
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Number of Participants Able to Walk From Baseline to 12 Months as Measured by 6-Minute Walk Test
Subjects able to walk at baseline
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2 Participants
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Number of Participants Able to Walk From Baseline to 12 Months as Measured by 6-Minute Walk Test
Subjects able to walk at 1 Month
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8 Participants
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Number of Participants Able to Walk From Baseline to 12 Months as Measured by 6-Minute Walk Test
Subjects able to walk at 3 Months
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9 Participants
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Number of Participants Able to Walk From Baseline to 12 Months as Measured by 6-Minute Walk Test
Subjects able to walk at 6 Months
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9 Participants
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Number of Participants Able to Walk From Baseline to 12 Months as Measured by 6-Minute Walk Test
Subjects able to walk at 12 Months
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9 Participants
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Adverse Events
BMMNC Treated Group
Serious adverse events
| Measure |
BMMNC Treated Group
n=17 participants at risk
All the subjects enrolled in the study were treated using autologous Bone Marrow Mononuclear Cells concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) and injected intra-muscularly into multiple sites in the ischemic muscle of the affected limb at 0.5 cc/injection for a total of 15-20 cc.
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Vascular disorders
Major Limb Amputation
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17.6%
3/17 • Number of events 3 • Adverse events were reported for the duration of the study, that is, from baseline to 12 Months
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Vascular disorders
Minor Limb Amputation
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11.8%
2/17 • Number of events 2 • Adverse events were reported for the duration of the study, that is, from baseline to 12 Months
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Cardiac disorders
Death
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11.8%
2/17 • Number of events 2 • Adverse events were reported for the duration of the study, that is, from baseline to 12 Months
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Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60