MOBILE: Safety and Efficacy Study of Autologous Concentrated Bone Marrow Aspirate (cBMA) for Critical Limb Ischemia (CLI)

• Sponsor: Zimmer Biomet (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01049919
• Collaborator: (none)
• Enrollment: 153
• Locations: 25
• Arms: 2
• Duration (Months): 116
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This trial will evaluate the safety and efficacy of concentrated bone marrow aspirate (cBMA) to prevent or delay major amputation and/or death in subjects with critical limb ischemia (CLI) due to severe peripheral arterial disease (PAD).

Condition or Disease	Intervention/Treatment	Phase
Critical Limb Ischemia; Peripheral Arterial Disease; Peripheral Vascular Disease	Device: Bone marrow concentration device; Procedure: Placebo procedure (sham)	N/A

Detailed Description

This is a prospective, randomized, double-blind, placebo controlled, multicenter trial intended for subjects with critical limb ischemia (CLI) that are unsuitable for revascularization. The investigational treatment utilizes autologous concentrated bone marrow aspirate (cBMA) at the point of care. The bone marrow aspirate is obtained from the subject's hip, concentrated with a bone marrow concentration device, and delivered intramuscularly to the affected limb. Subjects meeting the inclusion/exclusion criteria will be randomized to receive either the investigational treatment (cBMA) or a placebo control (sham treatment).

Study Design

• Study Type: Interventional
• Actual Enrollment: 153 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: MarrowStim PAD Kit for the Treatment of Critical Limb Ischemia (CLI) in Subjects With Severe Peripheral Arterial Disease (PAD)
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Feb 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Concentrated bone marrow aspirate (cBMA) Collection of autologous bone marrow aspirate and point-of-care concentration using the bone marrow concentration device, followed by intramuscular injection of concentrated bone marrow aspirate (cBMA) into the affected limb	Device: Bone marrow concentration device; Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb; Other Names: Bone marrow concentrate Bone marrow mononuclear cells MarrowStim
Sham Comparator: Placebo control (sham) Placebo procedure (sham) consists of simulated bone marrow aspiration followed by simulated intramuscular injections into the affected limb	Procedure: Placebo procedure (sham); Sham bone marrow aspiration, sham delivery to affected limb

Outcome Measures

Primary Outcome Measures

1. Occurrence of Major Amputation or Death [52 weeks]

   Occurrence of major amputation (above the ankle joint) or death.

Secondary Outcome Measures

1. Visual Analog Scale (VAS) - Pain [52 weeks]

   Pain reported at the 52-week follow-up visit as assessed on the visual analog scale (VAS). Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain." The distance from the beginning of the line is measured and reported in centimeters (cm), with 0 representing no pain and 10 representing the worst possible pain.

2. Six-Minute Walk Test [52 weeks]

   Measurement (in meters) of the total distance a participant is able to walk in 6 minutes. Since ability to walk is related to the condition of the affected limb, this measure is tied to limb pain and function. If a participant had multiple limbs included in the study, each limb was evaluated separately. Only one limb could be included in the study at a time.

Other Outcome Measures

1. Occurrence of Major Amputation or Death [5 years]

   Occurrence of major amputation (above the ankle joint) or death for all participants through final follow-up.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Unilateral or bilateral lower extremity ischemia due to advanced peripheral arterial disease

• Unsuitable for revascularization

• Minor tissue loss (Rutherford Category 5) or ischemic rest pain (Rutherford Category

1. with ABI ≤ 0.6, or TBI ≤ 0.4, or TcPO2 ≤ 50 mm Hg

• Competent to give consent

• No current malignancy or history of previous malignancy within the last five years, with the exception of adequately treated non-melanoma skin cancer (evidence of standard preventative cancer screenings required)

Exclusion Criteria:

• Major tissue loss (Rutherford Category 6)

• Diabetics on oral or insulin therapy with uncontrolled or untreated proliferative retinopathy (evidence of retinal exam required)

• Poorly controlled diabetes mellitus with HbA1C > 10% (evidence of HbA1C test required)

• Uncompensated congestive heart failure (New York Heart Association Class IV) and/or other conditions that preclude general anesthesia

• Myocardial infarction or stroke within last 90 days

• Elevated liver function tests (AST or ALT more than twice normal upper limit)

• Renal disease (creatinine > 2.5 mg/dl) or chronic hemodialysis

• White blood cell count < 3,000/µL or > 15,000/µL, platelet count < 100,000/µL, or hematocrit < 32%

• Topical growth hormone therapy within last 90 days, or injected growth hormone therapy within last 180 days

• Disease of central nervous system and/or other conditions that impair cognitive function

• Two or more episodes of pulmonary embolus with a documented DVT in index leg or history of DVT in index leg without evidence of clot resolution

• Current infection of index leg

• Pregnant women (negative urine pregnancy test required)

• Lower extremity venous disease with pitting edema in index leg

• Recent history (in the 6 months prior to screening) of bone marrow disease or treatment with any medication or procedure which adversely affects the bone marrow and would prohibit transplantation

• Current osteomyelitis in index leg

• Existing HIV diagnosis

• Organ transplant recipients

• Known terminal disease process with life expectancy less than one year

• Severe concomitant disease(s) or any additional condition(s) which the investigator feels constitute(s) criteria for exclusion of a particular subject

• Major amputation required within 30 days

• Inclusion in any other clinical study that may affect the outcome of this study

• Uncorrected stenosis(es) of greater than 50% in the common and/or external iliac artery and/or common femoral artery of the index leg.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Arkansas Veterans Healthcare System	Little Rock	Arkansas	United States	72205
2	University of California-Davis Medical Center	Sacramento	California	United States	95817
3	University of Miami	Miami	Florida	United States	33136
4	Piedmont Hospital	Atlanta	Georgia	United States	30309
5	Northwestern University	Chicago	Illinois	United States	60611
6	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
7	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
8	University of Louisville	Louisville	Kentucky	United States	40202
9	Tufts Medical Center	Boston	Massachusetts	United States	02111
10	UMass Memorial Health Care	Worcester	Massachusetts	United States	01655
11	Spectrum Health	Grand Rapids	Michigan	United States	49503
12	Saint Luke's Hospital	Kansas City	Missouri	United States	64111
13	Nebraska-Western Iowa VA Healthcare System	Omaha	Nebraska	United States	68105
14	Holy Name Medical Center	Teaneck	New Jersey	United States	07666
15	The Mount Sinai Hospital	New York	New York	United States	10029
16	Weill Cornell Medical College / New York-Presbyterian Hospital	New York	New York	United States	10065
17	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
18	The Cleveland Clinic	Cleveland	Ohio	United States	44195
19	Remington-Davis	Columbus	Ohio	United States	43215
20	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
21	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania	United States	15240
22	The Methodist Hospital	Houston	Texas	United States	77030
23	University of Virginia Hospital	Charlottesville	Virginia	United States	22908
24	Providence Sacred Heart Medical Center	Spokane	Washington	United States	99204
25	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215

Sponsors and Collaborators

• Zimmer Biomet

Investigators

• Principal Investigator: Michael P. Murphy, MD, Indiana University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

• Murphy MP, Lawson JH, Rapp BM, Dalsing MC, Klein J, Wilson MG, Hutchins GD, March KL. Autologous bone marrow mononuclear cell therapy is safe and promotes amputation-free survival in patients with critical limb ischemia. J Vasc Surg. 2011 Jun;53(6):1565-74.e1. doi: 10.1016/j.jvs.2011.01.074. Epub 2011 Apr 22.

• Responsible Party: Zimmer Biomet
• ClinicalTrials.gov Identifier: NCT01049919
• Other Study ID Numbers: BB-IDE 13996; BBIO.CR.CT002
• First Posted: Jan 15, 2010
• Last Update Posted: May 28, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Zimmer Biomet: Critical Limb Ischemia; Peripheral Arterial Disease; Peripheral Vascular Disease; CLI; PAD; PVD; Angiogenesis; Stem Cells; Cell Therapy; Limb Salvage; Amputation; Leg Pain
• Additional relevant MeSH terms: Peripheral Arterial Disease; Peripheral Vascular Diseases; Vascular Diseases; Ischemia

Study Results

Participant Flow

Recruitment Details

Enrollment in the study occurred between June 2010 and June 2015. Until February 2014, participants completing the initial 52-week follow-up period could choose to have their second limb randomized if the participant and limb continued to meet all study inclusion and exclusion criteria. Three (3) limbs were enrolled during this time, resulting in a total of 155 limbs in 152 participants that were included in the final intent-to treat analysis for the primary endpoint.

Pre-assignment Detail

Participants that provided informed consent, completed all screening assessments, and met all inclusion and exclusion criteria for the study went on to be randomized and undergo the study procedure.

Arm/Group Title	Concentrated Bone Marrow Aspirate (cBMA)	Placebo Control (Sham)
Arm/Group Description	Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Period Title: Overall Study
STARTED	117	36
COMPLETED	65	19
NOT COMPLETED	52	17

Baseline Characteristics

Arm/Group Title	Concentrated Bone Marrow Aspirate (cBMA)	Placebo Control (Sham)	Total
Arm/Group Description	Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb	Total of all reporting groups
Overall Participants	117	36	153
Overall Limbs	119	36	155
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.7 (11.9)	66.7 (12.2)	65.0 (11.9)
Sex: Female, Male (Limbs) [Count of Units]
Female	48	16	64
Male	71	20	91
Race/Ethnicity, Customized (Limbs) [Count of Units]
African-American	24	4	28
White (non-Hispanic)	91	27	118
White (Hispanic)	3	4	7
Other	1	1	2
Region of Enrollment (participants) [Number]
United States	117 100%	36 100%	153 100%
Rutherford Score (Limbs) [Count of Units]
Rutherford Score = 4	65	19	84
Rutherford Score = 5	54	17	71
Diabetic Status (Limbs) [Count of Units]
Diabetes = Yes	49	14	63
Diabetes = No	70	22	92

Outcome Measures

1. Primary Outcome

Title	Occurrence of Major Amputation or Death
Description	Occurrence of major amputation (above the ankle joint) or death.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

All limbs that were randomized to a treatment group were included in the analysis for the primary endpoint.

Arm/Group Title	Concentrated Bone Marrow Aspirate (cBMA)	Placebo Control (Sham)
Arm/Group Description	Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Measure Participants	117	36
Measure Limbs	119	36
Count of Units [Limbs]	24	11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concentrated Bone Marrow Aspirate (cBMA), Placebo Control (Sham)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.224
	Comments
	Method	Proportional Hazards Regression
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; 0.31 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Visual Analog Scale (VAS) - Pain
Description	Pain reported at the 52-week follow-up visit as assessed on the visual analog scale (VAS). Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" and "worst pain." The distance from the beginning of the line is measured and reported in centimeters (cm), with 0 representing no pain and 10 representing the worst possible pain.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

All limbs that were randomized to a treatment group, did not meet a primary endpoint or otherwise exit from the study, and that had an assessment available at 52 weeks were included in the analysis.

Arm/Group Title	Concentrated Bone Marrow Aspirate (cBMA)	Placebo Control (Sham)
Arm/Group Description	Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Measure Participants	117	36
Measure Limbs	119	36
Baseline	6.462 (7.789)	5.836 (2.680)
52 Weeks	3.651 (2.964)	3.346 (3.019)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concentrated Bone Marrow Aspirate (cBMA), Placebo Control (Sham)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.671
	Comments	Treatment-by-week p-value is reported.
	Method	Repeated measures model
	Comments	The statistical analysis model includes treatment group, week, treatment-by-week, and baseline pain measurement.

3. Secondary Outcome

Title	Six-Minute Walk Test
Description	Measurement (in meters) of the total distance a participant is able to walk in 6 minutes. Since ability to walk is related to the condition of the affected limb, this measure is tied to limb pain and function. If a participant had multiple limbs included in the study, each limb was evaluated separately. Only one limb could be included in the study at a time.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

All limbs that were randomized to a treatment group, did not meet a primary endpoint or otherwise exit from the study, and that had an assessment available at 52 weeks were included in the analysis.

Arm/Group Title	Concentrated Bone Marrow Aspirate (cBMA)	Placebo Control (Sham)
Arm/Group Description	Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Measure Participants	117	36
Measure Limbs	119	36
Baseline	158.508 (115.157)	173.114 (130.397)
52 Weeks	223.545 (170.015)	218.352 (148.226)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concentrated Bone Marrow Aspirate (cBMA), Placebo Control (Sham)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.714
	Comments	Treatment-by-week p-value is reported.
	Method	Repeated measures model
	Comments	The statistical analysis model includes treatment group, week, treatment-by-week, and baseline pain measurement.

4. Other Pre-specified Outcome

Title	Occurrence of Major Amputation or Death
Description	Occurrence of major amputation (above the ankle joint) or death for all participants through final follow-up.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

All randomized participants were included in the analysis. Some participants did not re-consent for follow-up after 52 weeks and as such their long-term status is unknown. For the purposes of this analysis, they are counted with those who completed follow-up. Control participants that received crossover therapy with cBMA after 52 weeks are counted with the control group.

Arm/Group Title	Concentrated Bone Marrow Aspirate (cBMA)	Placebo Control (Sham)
Arm/Group Description	Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Measure Participants	117	36
Measure Limbs	119	36
Count of Units [Limbs]	36	16

5. Post-Hoc Outcome

Title	Occurrence of Major Amputation or Death, Excluding Rutherford 5 Diabetic Subjects
Description	Occurrence of major amputation (above the ankle joint) or death, excluding the subgroup of subjects with Rutherford Category 5 critical limb ischemia and diabetes. The Rutherford score is a classification of severity for peripheral artery disease which ranges from 0 (asymptomatic) to 6 (major tissue loss extending above the transmetatarsal level, functional foot no longer salvageable). The study enrolled participants with Rutherford scores of 4 (ischemic rest pain) and 5 (minor tissue loss, nonhealing ulcer, and/or focal dry gangrene).
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

All limbs for subjects from the following subgroups that were randomized to a treatment group were included in this post-hoc analysis: Rutherford Category 4 and diabetic, Rutherford Category 4 and non-diabetic, Rutherford Category 5 and non-diabetic.

Arm/Group Title	Concentrated Bone Marrow Aspirate (cBMA)	Placebo Control (Sham)
Arm/Group Description	Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb	Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
Measure Participants	92	30
Measure Limbs	94	30
Count of Units [Limbs]	13	10

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Concentrated Bone Marrow Aspirate (cBMA), Placebo Control (Sham)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	Proportional Hazards Regression
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.37
	Confidence Interval	(2-Sided) 95%; 0.16 to 0.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	All adverse events occurring from the start of study treatment up to the 52-week follow-up visit were recorded. Between 52 weeks and 5 years, only major adverse limb events, including those resulting in major amputation, and death were recorded. Serious adverse events are reported through 52 weeks. All-cause mortality is reported through 5 years. Not all participants re-consented to additional follow-up after week 52, so mortality information was only available for those that re-consented.
Adverse Event Reporting Description	Participants were asked to report adverse events during all follow-up visits, and site staff were to review medical records available between visits to determine if additional events had occurred that were not reported by participants. Although some events were not limb-related, they were recorded and counted for each enrolled limb. If a participant had multiple limbs included in the study, events for each limb were evaluated separately. Only one limb was included in the study at a time.
Arm/Group Title	Concentrated Bone Marrow Aspirate (cBMA)		Placebo Control (Sham)
Arm/Group Description	Bone marrow concentration device: Concentration of autologous bone marrow aspirate for intramuscular delivery to affected limb		Placebo procedure (sham): Sham bone marrow aspiration, sham delivery to affected limb
All Cause Mortality
	Concentrated Bone Marrow Aspirate (cBMA)		Placebo Control (Sham)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/119 (9.2%)		7/36 (19.4%)
Serious Adverse Events
	Concentrated Bone Marrow Aspirate (cBMA)		Placebo Control (Sham)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/119 (55.5%)		24/36 (66.7%)
Blood and lymphatic system disorders
Low Red Blood Cell-Related Level	2/119 (1.7%)		1/36 (2.8%)
Hemorrhagic Anemia	0/119 (0%)		1/36 (2.8%)
Cardiac disorders
Acute Congestive Heart Failure	3/119 (2.5%)		2/36 (5.6%)
Chest Pain	3/119 (2.5%)		3/36 (8.3%)
Atrial Fibrillation	2/119 (1.7%)		0/36 (0%)
Asystole Episode	1/119 (0.8%)		0/36 (0%)
Bradycardia	1/119 (0.8%)		0/36 (0%)
Cardiac Decompensation	1/119 (0.8%)		0/36 (0%)
Myocardial Infarction	1/119 (0.8%)		0/36 (0%)
Shortness of Breath	1/119 (0.8%)		0/36 (0%)
Gastrointestinal disorders
Gastrointestinal Bleed	1/119 (0.8%)		2/36 (5.6%)
Ischemic Bowel	2/119 (1.7%)		0/36 (0%)
Nausea/Vomiting	2/119 (1.7%)		0/36 (0%)
Gastric Ulcer	0/119 (0%)		1/36 (2.8%)
Ileocolic Anastomotic Leak	1/119 (0.8%)		0/36 (0%)
Large Bowel Obstruction	1/119 (0.8%)		0/36 (0%)
General disorders
Death	5/119 (4.2%)		3/36 (8.3%)
Abdominal Pain	2/119 (1.7%)		0/36 (0%)
General Weakness	0/119 (0%)		1/36 (2.8%)
Hematoma	1/119 (0.8%)		0/36 (0%)
Non-Healing of Toe Amputation Site	1/119 (0.8%)		0/36 (0%)
Prolonged Hospitalization	1/119 (0.8%)		0/36 (0%)
Hepatobiliary disorders
Cholelithiasis	1/119 (0.8%)		0/36 (0%)
Immune system disorders
Anaphylaxis Related to Antibiotic	0/119 (0%)		1/36 (2.8%)
Infections and infestations
Cellulitis - Index Leg	7/119 (5.9%)		3/36 (8.3%)
Pneumonia	6/119 (5%)		1/36 (2.8%)
Infection - Index Leg	4/119 (3.4%)		0/36 (0%)
Osteomyelitis - Index Leg	4/119 (3.4%)		0/36 (0%)
Sepsis	1/119 (0.8%)		1/36 (2.8%)
Abdominal Sepsis/Shock	1/119 (0.8%)		0/36 (0%)
Bacteremia	1/119 (0.8%)		0/36 (0%)
Cellulitis - Arm	1/119 (0.8%)		0/36 (0%)
Cellulitis - Bilateral Legs	1/119 (0.8%)		0/36 (0%)
Cellulitis - Contralateral Leg	1/119 (0.8%)		0/36 (0%)
Infected Abdominal Mesh	1/119 (0.8%)		0/36 (0%)
Infection - Contralateral Leg	1/119 (0.8%)		0/36 (0%)
Intra-Abdominal Abscess	1/119 (0.8%)		0/36 (0%)
Osteomyelitis - Contralateral Leg	1/119 (0.8%)		0/36 (0%)
Urinary Tract Infection	1/119 (0.8%)		0/36 (0%)
Injury, poisoning and procedural complications
Fall	1/119 (0.8%)		0/36 (0%)
Fracture - Contralateral Leg	1/119 (0.8%)		0/36 (0%)
Subarachnoid Hemorrhage	1/119 (0.8%)		0/36 (0%)
Investigations
Hyperglycemia	1/119 (0.8%)		0/36 (0%)
Metabolic Acidosis	1/119 (0.8%)		0/36 (0%)
Metabolism and nutrition disorders
Hypomagnesemia	0/119 (0%)		1/36 (2.8%)
Weakness - Hand	0/119 (0%)		1/36 (2.8%)
Diabetic Ketoacidosis	1/119 (0.8%)		0/36 (0%)
Hyperkalemia	1/119 (0.8%)		0/36 (0%)
Musculoskeletal and connective tissue disorders
Pain - Index Leg	7/119 (5.9%)		6/36 (16.7%)
Degenerative Disc - Cervical Spine	1/119 (0.8%)		0/36 (0%)
Pain - Contralateral Leg	1/119 (0.8%)		0/36 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanoma	1/119 (0.8%)		0/36 (0%)
Nervous system disorders
Oversedation	1/119 (0.8%)		0/36 (0%)
Renal and urinary disorders
Acute Kidney Injury	1/119 (0.8%)		2/36 (5.6%)
Hematuria	0/119 (0%)		1/36 (2.8%)
Urinary Retention	1/119 (0.8%)		0/36 (0%)
Reproductive system and breast disorders
Fibroids	1/119 (0.8%)		0/36 (0%)
Menstruation	1/119 (0.8%)		0/36 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	1/119 (0.8%)		4/36 (11.1%)
Skin and subcutaneous tissue disorders
Gangrene - Index Leg	7/119 (5.9%)		0/36 (0%)
Wound - Index Leg	5/119 (4.2%)		1/36 (2.8%)
Ulceration - Index Leg	0/119 (0%)		2/36 (5.6%)
Wound - Contralateral Leg	1/119 (0.8%)		1/36 (2.8%)
Abscess - Buttock	1/119 (0.8%)		0/36 (0%)
Ulceration - Contralateral Leg	1/119 (0.8%)		0/36 (0%)
Surgical and medical procedures
Major Amputation - Index Leg	19/119 (16%)		8/36 (22.2%)
Toe Amputation - Index Leg	5/119 (4.2%)		2/36 (5.6%)
Bypass Graft - Index Leg	1/119 (0.8%)		2/36 (5.6%)
Amputation of Foot - Contralateral Foot	0/119 (0%)		1/36 (2.8%)
Amputation of Toe - Contralateral Leg	0/119 (0%)		1/36 (2.8%)
Major Amputation - Contralateral Leg	0/119 (0%)		1/36 (2.8%)
Angioplasty - Contralateral Leg	1/119 (0.8%)		0/36 (0%)
Angioplasty - Index Leg	1/119 (0.8%)		0/36 (0%)
Elective Surgery	1/119 (0.8%)		0/36 (0%)
Knee Revision - Index Leg	1/119 (0.8%)		0/36 (0%)
Vascular disorders
Ischemia - Index Leg	4/119 (3.4%)		3/36 (8.3%)
Stroke	2/119 (1.7%)		1/36 (2.8%)
Non-ST-Elevation Myocardial Infarction	0/119 (0%)		1/36 (2.8%)
Shock	0/119 (0%)		1/36 (2.8%)
Cardiac Ischemia	1/119 (0.8%)		0/36 (0%)
Carotid Blockage	1/119 (0.8%)		0/36 (0%)
Deep Vein Thrombosis - Index Leg	1/119 (0.8%)		0/36 (0%)
Deconditioning	1/119 (0.8%)		0/36 (0%)
Near Syncope	1/119 (0.8%)		0/36 (0%)
Peripheral Artery Disease	1/119 (0.8%)		0/36 (0%)
Superior Mesenteric Artery Thrombus	1/119 (0.8%)		0/36 (0%)
Stenosis of Bypass Graft - Index Leg	1/119 (0.8%)		0/36 (0%)
Syncope	1/119 (0.8%)		0/36 (0%)
Venous Thromboembolism - Contralateral Leg	1/119 (0.8%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Concentrated Bone Marrow Aspirate (cBMA)		Placebo Control (Sham)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	117/119 (98.3%)		35/36 (97.2%)
Blood and lymphatic system disorders
Low Red Blood Cell-Related Level	87/119 (73.1%)		13/36 (36.1%)
Low White Blood Cell-Related Level	17/119 (14.3%)		5/36 (13.9%)
High White Blood Cell-Related Level	11/119 (9.2%)		2/36 (5.6%)
High Red Blood Cell-Related Level	5/119 (4.2%)		2/36 (5.6%)
Cardiac disorders
Acute Congestive Heart Failure	4/119 (3.4%)		2/36 (5.6%)
Gastrointestinal disorders
Nausea/Vomiting	8/119 (6.7%)		4/36 (11.1%)
General disorders
Pain - Bilateral Iliac Crests	30/119 (25.2%)		4/36 (11.1%)
Fever	2/119 (1.7%)		4/36 (11.1%)
Infections and infestations
Cellulitis - Index Leg	14/119 (11.8%)		4/36 (11.1%)
Pneumonia	7/119 (5.9%)		3/36 (8.3%)
Infection - Index Leg	10/119 (8.4%)		0/36 (0%)
Respiratory Infection	4/119 (3.4%)		3/36 (8.3%)
Urinary Tract Infection	5/119 (4.2%)		2/36 (5.6%)
Metabolism and nutrition disorders
Edema - Index Leg	12/119 (10.1%)		2/36 (5.6%)
Hyperglycemia	6/119 (5%)		0/36 (0%)
Musculoskeletal and connective tissue disorders
Pain - Index Leg	62/119 (52.1%)		22/36 (61.1%)
Pain - Back	10/119 (8.4%)		2/36 (5.6%)
Pain - Hip	1/119 (0.8%)		2/36 (5.6%)
Nervous system disorders
Dizziness	3/119 (2.5%)		2/36 (5.6%)
Headache	3/119 (2.5%)		2/36 (5.6%)
Numbness - Index Leg	1/119 (0.8%)		2/36 (5.6%)
Psychiatric disorders
Insomnia	2/119 (1.7%)		2/36 (5.6%)
Renal and urinary disorders
Urinary Retention	6/119 (5%)		1/36 (2.8%)
Acute Kidney Injury	4/119 (3.4%)		2/36 (5.6%)
Respiratory, thoracic and mediastinal disorders
Cough	2/119 (1.7%)		2/36 (5.6%)
Skin and subcutaneous tissue disorders
Ulceration - Index Leg	17/119 (14.3%)		8/36 (22.2%)
Erythema - Index Leg	9/119 (7.6%)		5/36 (13.9%)
Wound - Index Leg	15/119 (12.6%)		7/36 (19.4%)
Gangrene - Index Leg	9/119 (7.6%)		1/36 (2.8%)
Fissure - Index Leg	1/119 (0.8%)		2/36 (5.6%)
Pruritis - Index Leg	0/119 (0%)		2/36 (5.6%)
Surgical and medical procedures
Bypass Graft - Index Leg	2/119 (1.7%)		2/36 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.