Bone Marrow Aspirate Concentrate (BMAC) for Treatment of Critical Limb Ischemia (CLI)

Study Overview
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Brief Summary
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Critical Limb Ischemia prevents the legs and feet from receiving oxygen and nutrients needed for proper function. This severe lack of blood flow can lead to painful legs while walking or at rest and can result in foot sores, ulcers, gangrene, and even amputation. The purpose of this study is to determine if injections of concentrated bone marrow into damaged tissues will result in improved blood flow. If successful, this treatment could improve blood flow to the lower limb, reduce pain, and reduce the frequency of limb amputations.

Detailed Description
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Bone marrow aspirate is collected and processed by centrifugation to remove red blood cells. The resulting concentrate of cells is injected into ischemic tissues of the lower limb. The purpose of this study is to determine if injections of concentrated bone marrow nucleated cells into ischemic tissues will result in vasculogenesis.

Official Title
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Pivotal Study of the Safety and Effectiveness of Autologous Bone Marrow Aspirate Concentrate (BMAC) for the Treatment of Critical Limb Ischemia Due to Peripheral Arterial Disease

Conditions
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Critical Limb Ischemia

Intervention / Treatment
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* Device: BMAC injection
* Device: Placebo injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has Peripheral Arterial Occlusive Disease (PAOD) with clinical Rutherford Category 5 disease, as defined in the reporting standards adopted by the Society of Vascular Surgeons(table 1); Minor Tissue loss-focal gangrene with diffuse pedal ischemia Patient meets at least one of the following diagnostic criteria in the study limb: Ankle artery occlusion pressure absolute ≤60 mmHg or ABI ≤0.6 Toe artery occlusive pressure < 50mm Hg or TBI ≤0.6 There is no reasonable open surgical or endovascular revascularization option as determined by the treating vascular specialist. Factors that may contribute to the determination of inoperability may include: Anatomical considerations No outflow targets No appropriate conduit (i.e. vein for bypass) Long segment occlusions or calcified lesions that predict poor outcome with endovascular approaches. High risk medical conditions i.e. Unstable cardiac disease. History of prior failed revascularization attempts The Patient's case was reviewed at the treating institution's Multidisciplinary Vascular Conference where the patient's status as a poor candidate for conventional therapies was confirmed. Age ≥18 years and ability to understand the planned treatment Subject has read and signed the IRB approved Informed Consent form Patients for whom the following medication(s) is prescribed must have a one month stable baseline therapy prior to enrollment: Plavix/asprin therapy, anticoagulation therapy, cholesterol lowering agent, and or blood pressure medication. If any of these medications are not prescribed notation of the reason for omission is to be provided. Hematocrit ≥ 28.0%, White Blood Cell count ≤ 14,000, Platelet count ≥ 50,000, Creatinine ≤ 2.5 mg / dL, INR ≤ 1.6 unless on Coumadin, or PTT <1.5 x control (to avoid bleeding complications) Patients on Coumadin will be corrected prior to the procedure and must have an INR<1.6 at the time of randomization/surgery. Exclusion Criteria: Life expectancy <6 months due to concomitant illnesses History of bone marrow diseases (especially NHL, MDS) that prohibit transplantation Terminal renal failure with existing dependence on dialysis or serum creatinine >2.5 mg/dL Known active malignancy or results outside of normal limits from the following tests: PAP, Chest X-ray, PSA, Mammogram, Hemocult unless follow-up studies reveal patient to be cancer free. Poorly controlled diabetes mellitus (HgbA1C>10%) Medical risk that precludes anesthesia (conscious sedation), or ASA Class 5 Life-threatening complications of the ischemia necessitating immediate amputation Uncorrected occlusion of the common or external iliac artery on index side Absence of any pulsatile Doppler flow below the ankle. Extensive necrosis of the index limb or other conditions that make amputation inevitable (Rutherford Category 6). Ulceration with exposed bone proximal to the distal metatarsal heads (ie. heel or mid foot) Active clinical infection or infection being treated by antibiotics within one week of enrollment Treatment with immunosuppressant drugs (including Prednisone > 5 mg per day). Female who is pregnant or nursing, or of child bearing potential and is not using a reliable birth control method. Underwent a major open cardiovascular surgical procedure (carotid endarterectomy, arterial aneurysm or bypass surgery, or coronary artery bypass surgery) or a myocardial infarction within the 3 months prior to randomization Underwent a successful or partially successful endovascular intervention for peripheral arterial occlusive disease. (ie. Aorta, iliac, femoral, popliteal, or tibial artery angioplasty, stenting, or atherectomy) within the prior 3 months. Endovascular coronary intervention (ie. Angioplasty, atherectomy, stenting) within 1 month prior to randomization. Underwent a failed attempt for endovascular revascularization during the prior 1 month. For the purpose of this exclusion criteria an endovascular procedure is considered a failure if: The procedure is diagnostic only with no intervention performed, (for example in the case where wire crossing can not be obtained). The treated artery recoils, thromboses, or dissects resulting in occlusion of the treated arterial segment, documented by intraoperative imaging. Note that endovascular procedures with suboptimal results but not meeting criteria 1 or 2 above may qualify for inclusion after 3 months as in #16 above. Cerebrovascular accident within 6 months prior to randomization. Treatment with topical growth factors or hyperbaric oxygen (HBO) within 30 days, or systemic growth factor treatment within 6 months of enrollment. Known hypersensitivity to heparin; or history of heparin-induced thrombocytopenia (HIT).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BMAC Treatment<br>Intervention- Injection of 40 ml of autologous bone marrow concentrate (BMAC injection) prepared with the SmartPReP2 BMAC System | Device: BMAC injection<br>* Injection of 40 ml of autologous bone marrow aspirate concentrate (BMAC injection) prepared with the SmartPReP2 BMAC System<br>|
| Placebo Comparator: Placebo Injection<br>Injection of placebo (diluted peripheral blood) into ischemic tissue of the lower extremity | Device: Placebo injection<br>* Injection of placebo into ischemic tissue of the lower extremity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amputation Free Survival | Survival without a major (above the ankle) amputation | Six Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change In Rutherford Classification | Change in the subjects clinical status as measured by Rutherford Classification | Six Months | 
| Change in Pain | Change in Subjects perception of pain as measured on a 100 mm visual analog scale | Six Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLI, Critical Limb Ischemia, PAOD, Peripheral Arterial Disease, Stem Cells, Limb amputation, Leg ulcers