Trial Outcomes & Findings for Use of Autologous Concentrated Bone Marrow Aspirate in Preventing Wound Complications in Below Knee Amputation (BKA) (NCT NCT02863926)
NCT ID: NCT02863926
Last Updated: 2024-12-12
Results Overview
Safety will be evaluated by review of treatment related AEs during the 12-month follow-up period. The study will be terminated in the event of a Grade 4-5 unexpected event based on the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Treatment-related AEs will be categorized overlapping systems and severities. Three categories of systems are cardiovascular, respiratory, or infectious. Two categories of severity will be serious adverse (SAE) and major adverse cardiac events (MACE). Binomial confidence Intervals at the 95% confidence level and p-values for these 3 groups will be calculated. Since previous trials have not reported AEs with cBMA treatment, confidence intervals will be generated by the method of the Wilson Score Interval.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
6 participants
Primary outcome timeframe
12 months
Results posted on
2024-12-12
Participant Flow
Eligible patients were invited to participate in the study on a first-come basis, recruited from the Investigator's patient population and by referrals from other physicians who have patients recommended for major amputation. The study team received referrals after the patient was seen by their own vascular or orthopedic specialist and the amputation was recommended to them.
Of 7 screened patients, 6 met inclusion criteria and were treated.
Participant milestones
| Measure |
Day 7
BKA performed at 7 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
Day 21
BKA performed at 21 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
1
|
|
Overall Study
Per Protocol Population Week 6
|
4
|
1
|
|
Overall Study
Per Protocol Population Week 52
|
3
|
0
|
|
Overall Study
COMPLETED
|
3
|
0
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Day 7
BKA performed at 7 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
Day 21
BKA performed at 21 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
|---|---|---|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
Baseline Characteristics
Use of Autologous Concentrated Bone Marrow Aspirate in Preventing Wound Complications in Below Knee Amputation (BKA)
Baseline characteristics by cohort
| Measure |
Day 7
n=5 Participants
BKA performed at 7 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
Day 21
n=1 Participants
BKA performed at 21 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
Total
n=6 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Continuous
|
62.4 years
STANDARD_DEVIATION 5.57 • n=5 Participants
|
66 years
STANDARD_DEVIATION 0 • n=7 Participants
|
63 years
STANDARD_DEVIATION 5.26 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Current Smoker
|
4 participants
n=5 Participants
|
1 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Diabetes Mellitus
|
5 participants
n=5 Participants
|
1 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Hgb A1C %
|
9.04 percentage of glycated hemoglobin
STANDARD_DEVIATION 1.46 • n=5 Participants
|
8.0 percentage of glycated hemoglobin
STANDARD_DEVIATION 0 • n=7 Participants
|
8.52 percentage of glycated hemoglobin
STANDARD_DEVIATION 0.52 • n=5 Participants
|
|
Systolic Blood Pressure
|
122 Pressure during heartbeat in mmHg
STANDARD_DEVIATION 27.6 • n=5 Participants
|
187 Pressure during heartbeat in mmHg
STANDARD_DEVIATION 0 • n=7 Participants
|
133 Pressure during heartbeat in mmHg
STANDARD_DEVIATION 35.0 • n=5 Participants
|
|
Diastolic Blood Pressure
|
68.8 Pressure between heartbeats in mmHg
STANDARD_DEVIATION 71.5 • n=5 Participants
|
85 Pressure between heartbeats in mmHg
STANDARD_DEVIATION 0 • n=7 Participants
|
71.5 Pressure between heartbeats in mmHg
STANDARD_DEVIATION 9.2 • n=5 Participants
|
|
Body Mass index (BMI)
|
31.62 weight in kg/height in meters^2
STANDARD_DEVIATION 3.41 • n=5 Participants
|
24.5 weight in kg/height in meters^2
STANDARD_DEVIATION 0 • n=7 Participants
|
30.43 weight in kg/height in meters^2
STANDARD_DEVIATION 4.09 • n=5 Participants
|
|
eGFR
|
61.96 Renal filtration rate in mg/mmol
STANDARD_DEVIATION 36.1 • n=5 Participants
|
52 Renal filtration rate in mg/mmol
STANDARD_DEVIATION 0 • n=7 Participants
|
60.3 Renal filtration rate in mg/mmol
STANDARD_DEVIATION 33.17 • n=5 Participants
|
|
Index Leg TcPO2
|
35.25 Oxygen level at skin in mmHg
STANDARD_DEVIATION 21.69 • n=5 Participants
|
0 Oxygen level at skin in mmHg
STANDARD_DEVIATION 0 • n=7 Participants
|
35.25 Oxygen level at skin in mmHg
STANDARD_DEVIATION 21.69 • n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsSafety will be evaluated by review of treatment related AEs during the 12-month follow-up period. The study will be terminated in the event of a Grade 4-5 unexpected event based on the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Treatment-related AEs will be categorized overlapping systems and severities. Three categories of systems are cardiovascular, respiratory, or infectious. Two categories of severity will be serious adverse (SAE) and major adverse cardiac events (MACE). Binomial confidence Intervals at the 95% confidence level and p-values for these 3 groups will be calculated. Since previous trials have not reported AEs with cBMA treatment, confidence intervals will be generated by the method of the Wilson Score Interval.
Outcome measures
| Measure |
Day 7
n=5 Participants
BKA performed at 7 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
Day 21
n=1 Participants
BKA performed at 21 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
|---|---|---|
|
Number of Participants With Treatment-related Adverse Events Occurring During the Enrollment Period as Assessed by the Investigator Using the CTCAE 4.0 Scale.
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 12 monthsDocumentation will be collected on wound complications at the below knee amputation surgical site resulting in necessity of revision/conversion to above knee amputation.
Outcome measures
| Measure |
Day 7
n=5 Participants
BKA performed at 7 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
Day 21
n=1 Participants
BKA performed at 21 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
|---|---|---|
|
Number of Participants With Conversion From Below Knee Amputation to Above Knee Amputation as Evidenced by Wound Complications at the Below Knee Amputation Stump Site.
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Immunostaining for the CD31 antigen was selected to measure the capillary density, reported as CD31-positive features normalized to fiber number. For capillary density quantification, CD31 positive profiles were counted using a custom algorithm and nuclei were counted using a pipeline that we designed in CellProfiler.
Continuous confidence intervals at the 95% level will be constructed to explore differences among the time-tiered administration of MSC for the quantity of capillary density in muscle fibers.
Outcome measures
| Measure |
Day 7
n=5 Participants
BKA performed at 7 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
Day 21
n=1 Participants
BKA performed at 21 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
|---|---|---|
|
The Role of Autologous Bone Marrow Cells Injected in Human Skeletal Muscle in Inducing Capillary Vessel Formation at the Time of Below Knee Amputation.
Proximal ATM Segment A
|
1.089 CD31-positive capillaries/fiber
Standard Error 0.052
|
1.431 CD31-positive capillaries/fiber
Standard Error 0.553
|
|
The Role of Autologous Bone Marrow Cells Injected in Human Skeletal Muscle in Inducing Capillary Vessel Formation at the Time of Below Knee Amputation.
Distal ATM Segment B
|
1.373 CD31-positive capillaries/fiber
Standard Error 0.050
|
1.673 CD31-positive capillaries/fiber
Standard Error 0.232
|
|
The Role of Autologous Bone Marrow Cells Injected in Human Skeletal Muscle in Inducing Capillary Vessel Formation at the Time of Below Knee Amputation.
Distal ATM Segment C
|
1.064 CD31-positive capillaries/fiber
Standard Error 0.056
|
1.526 CD31-positive capillaries/fiber
Standard Error 0.508
|
|
The Role of Autologous Bone Marrow Cells Injected in Human Skeletal Muscle in Inducing Capillary Vessel Formation at the Time of Below Knee Amputation.
Distal ATM Segment D
|
1.065 CD31-positive capillaries/fiber
Standard Error 0.064
|
1.197 CD31-positive capillaries/fiber
Standard Error 0.460
|
|
The Role of Autologous Bone Marrow Cells Injected in Human Skeletal Muscle in Inducing Capillary Vessel Formation at the Time of Below Knee Amputation.
Control Segment - Soleus
|
1.191 CD31-positive capillaries/fiber
Standard Error 0.104
|
NA CD31-positive capillaries/fiber
Standard Error NA
For this one patient in "Day 21" group, we did not have enough appropriate soleus tissue specimen for completing the ICC analysis.
|
Adverse Events
Day 7
Serious events: 4 serious events
Other events: 5 other events
Deaths: 0 deaths
Day 21
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Day 7
n=5 participants at risk
BKA performed at 7 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
Day 21
n=1 participants at risk
BKA performed at 21 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
|---|---|---|
|
Injury, poisoning and procedural complications
Wound dehiscence at amputation site
|
40.0%
2/5 • Number of events 2 • 12 months
|
0.00%
0/1 • 12 months
|
|
Metabolism and nutrition disorders
Glucose intolerance
|
20.0%
1/5 • Number of events 2 • 12 months
|
0.00%
0/1 • 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
20.0%
1/5 • Number of events 1 • 12 months
|
0.00%
0/1 • 12 months
|
|
Vascular disorders
Peripheral ischemia, non-index leg
|
20.0%
1/5 • Number of events 1 • 12 months
|
0.00%
0/1 • 12 months
|
|
Infections and infestations
Wound infection, non-index leg
|
20.0%
1/5 • Number of events 1 • 12 months
|
0.00%
0/1 • 12 months
|
|
Vascular disorders
Major amputation, non-index leg
|
20.0%
1/5 • Number of events 1 • 12 months
|
0.00%
0/1 • 12 months
|
|
Psychiatric disorders
Depression, worsening
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 1 • 12 months
|
|
Injury, poisoning and procedural complications
Seroma at amputation site, index leg
|
20.0%
1/5 • Number of events 1 • 12 months
|
0.00%
0/1 • 12 months
|
|
Renal and urinary disorders
Chronic kidney disease with acute kidney injury
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 1 • 12 months
|
|
Blood and lymphatic system disorders
Sepsis
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 1 • 12 months
|
|
Vascular disorders
Above Knee Amputation
|
0.00%
0/5 • 12 months
|
0.00%
0/1 • 12 months
|
Other adverse events
| Measure |
Day 7
n=5 participants at risk
BKA performed at 7 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
Day 21
n=1 participants at risk
BKA performed at 21 days post autologous cBMA injection. Injection of cBMA aspirate into the index leg
Injection of cBMA aspirate into the index leg: Injection of cBMA into the anterior tibialis muscle and upper index leg of subjects scheduled for semi-elective BKA 7-21 days before surgery
|
|---|---|---|
|
General disorders
Pain at amputation site
|
80.0%
4/5 • Number of events 4 • 12 months
|
0.00%
0/1 • 12 months
|
|
Vascular disorders
Wound developed on non-index foot
|
20.0%
1/5 • Number of events 1 • 12 months
|
0.00%
0/1 • 12 months
|
|
Gastrointestinal disorders
Nausea
|
20.0%
1/5 • Number of events 1 • 12 months
|
0.00%
0/1 • 12 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 1 • 12 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 2 • 12 months
|
|
Gastrointestinal disorders
Oral Candidiasis
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 1 • 12 months
|
|
Blood and lymphatic system disorders
Chronic anemia, worsening
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 1 • 12 months
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 1 • 12 months
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 1 • 12 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 1 • 12 months
|
|
Injury, poisoning and procedural complications
Wound, non-index extremity
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 1 • 12 months
|
|
Cardiac disorders
Chronic hypertension, worsening
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 1 • 12 months
|
|
General disorders
Fever of unknown origin
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 1 • 12 months
|
|
Nervous system disorders
Depression
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 2 • 12 months
|
|
Injury, poisoning and procedural complications
Skin integrity worsening, amputation site
|
0.00%
0/5 • 12 months
|
100.0%
1/1 • Number of events 2 • 12 months
|
|
Investigations
Iliac crest pain, post bone marrow aspiration
|
20.0%
1/5 • Number of events 1 • 12 months
|
0.00%
0/1 • 12 months
|
Additional Information
Kristen Wanczyk / Certified Clinical Research Nurse Coordinator
Indiana University School of Medicine
Phone: 317-7988-9548
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place