Peripheral Arterial Disease
Conditions
Keywords
Peripheral Arterial Diseases, Peripheral Artery Diseases, Arterial Occlusive Diseases, Peripheral Vascular Diseases
Brief summary
To evaluate the safety and effectiveness of the Cardio Flow FreedomFlow™ Orbital Circumferential Atherectomy System for atherosclerotic plaque removal and vessel compliance modification in de novo native target lesions in the peripheral vasculature of the lower extremities.
Detailed description
The FAST II study is a prospective, multi-center, non-randomized single-arm trial designed to evaluate the safety and effectiveness of the FreedomFlow™ Orbital Circumferential Atherectomy System in subjects diagnosed with peripheral arterial disease (PAD) of the lower extremities. The FreedomFlow™ Orbital Circumferential Atherectomy System is a minimally invasive, catheter-based system designed for improving luminal diameter and modifying vessel wall compliance in patients with PAD. The FreedomFlow™ Orbital Circumferential Atherectomy System is indicated to remove atherosclerotic plaque and modifying vessel wall compliance within peripheral arterial vessels. The therapy is intended for patients who are acceptable candidates for percutaneous transluminal atherectomy. The objective of the study is to evaluate the safety and effectiveness of the FreedomFlow™ Orbital Circumferential Atherectomy System for atherosclerotic plaque removal and vessel modification in de novo target lesions in the peripheral vasculature of the lower extremities.
Interventions
DEVICEOrbital Circumferential Atherectomy
Remove atherosclerotic plaque and modify vessel wall compliance within peripheral arterial vessels. The therapy is intended for patients who are acceptable candidates for percutaneous transluminal atherectomy.
Sponsors
Libra Medical
Cardio Flow, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
prospective, multi-center, non-randomized single-arm study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following criteria to be eligible for participation in the study: Inclusion Criteria 1. Age ≥ 18 years old. 2. Subject is a candidate for percutaneous endovascular intervention for peripheral vascular disease in the lower extremity. 3. Objective hemodynamic criteria that subject has a resting ankle-brachial index (ABI) ≤ 0.90 OR a resting toe-brachial index (TBI) of ≤ 0.80 OR ankle pressure of ≤70 mmHg. 4. Clinical presentation of lifestyle limiting claudication, rest pain and/or ischemic wounds as characterized by Rutherford Classification 2, 3, 4, or 5. 5. Disease is located in the common femoral, superficial femoral, popliteal, tibioperoneal, anterior tibial, posterior tibial, and/or peroneal arteries. 1. De novo target lesion(s) with stenosis ≥70% by visual estimation and/or 2. Lesion(s) treated by percutaneous transluminal angioplasty (PTA) and/or atherectomy ≥3 months prior with a restenosis ≥70% by visual estimation. 3. Up to three lesions can be treated at the index procedure provided the cumulative total lesion length is ≤ 20 cm AND all lesions are in the same target leg. 6. Target reference vessel diameter (proximal to and distal to target lesion) is 2 to 8 mm by angiographic visual estimation. 7. At least one patent vessel run-off to the ankle or foot at baseline. 8. The target lesion(s) can be successfully crossed with a commercially available 0.014 atherectomy guidewire without any complications during wiring procedure. 9. Subject signs a written Informed Consent form to participate in the study, prior to any study mandated determinations or procedure. Subject must be excluded from participation in this study if any of the following criteria are met:
Exclusion criteria
1. Is female with childbearing potential not taking adequate contraceptives or is currently breastfeeding. 2. Target lesion is within a native graft or synthetic graft. 3. Target lesion is an in-stent restenosis. 4. Target lesion is a chronic total occlusion (CTO) with occlusion length greater than 10 cm and/or with wire crossed sub-intimally. CTO wire placement in true lumen must be confirmed via Intra-vascular ultrasound (IVUS) prior to enrollment. 5. Subject has significant stenosis or occlusion of inflow tract (upstream disease) not successfully treated during the index procedure and prior to treatment of the target lesion. 6. Intra-operative (intra-procedure) clinical or angiographic complication (other than non-flow limiting dissections) attributed to the use of a currently marketed device prior to introduction of the Cardio Flow atherectomy drive shaft. 7. Evidence or history of aneurysmal target vessel. 8. Clinical/angiographic evidence of distal embolization prior to intervention. 9. History of an endovascular procedure or open vascular surgery on the index limb within 30 days prior to the index procedure. Endovascular procedure or open vascular surgery on the non-index limb cannot be staged within 2 weeks prior to the index procedure. 10. Planned endovascular or surgical procedure prior to the subject's 30 day follow up. 11. Signs and symptoms of systemic infection (temperature of ≥ 38.0° Celsius and/or white blood cell count (WBC) of ≥ 12,000 cells/µL) at the time of assessment; Note: If infection is adequately treated and controlled (temperature \< 38.0° C and WBC \< 12,000 cells/µL) patient may be enrolled. 12. Unstable coronary artery disease or other comorbid condition(s) that, in the judgment of the physician precludes safe percutaneous intervention. 13. Significant acute or chronic kidney disease with a creatinine level \> 2.5mg/dL and/or requiring dialysis. 14. Evidence of intracranial or gastrointestinal bleeding, intracranial aneurysm, myocardial infarction or stoke within 2 months of index procedure. 15. Known allergy to contrast agents or medications used to perform endovascular intervention that cannot be adequately pre-treated. 16. Subjects in whom anti-platelet, anticoagulant, or thrombolytic therapy is contraindicated. 17. Heparin-induced thrombocytopenia (HIT) not able to use Bivalirudin. 18. Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count less than 125,000/mm2, known coagulopathy, or international normalized ratio (INR) \> 1.8. 19. Evidence of thrombus within target lesion or thrombolytic therapy within 2 weeks of the index procedure. 20. Has life expectancy \< 12 months in the opinion of the investigator. 21. Subject is unwilling or unable to comply with the follow-up study requirements. 22. Subject is currently participating in an investigational drug or another investigational device exemption (IDE) study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Technical Success | At the time of the index procedure, usually within one hour after starting the procedure | Defined as the ability of the Cardio Flow FreedomFlow™ Orbital Circumferential Atherectomy System to achieve a residual diameter stenosis ≤50% without adjunctive therapy. |
| Freedom From Major Adverse Events | 30 days | Primary safety endpoint is freedom from a composite of new onset major adverse events (MAE) at 30-day follow-up as adjudicated by an Independent Clinical Events Committee. This endpoint is evaluated on a per patient basis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ankle Brachia, Index (ABI) Measured at Baseline, 30 Days and 6 Months | 30 days and 6 months | ABI measured at baseline, 30 days and 6 months. ABI ranges from 0 to 1, with smaller values indicating more severe disease. Normal ABI is 1. |
| Rutherford Classification | 30 days and 6 months | Change in Rutherford Classification at 30 days and 6 months. Rutherford scale ranges from 0 to 6 with higher values indicating more severe disease. Rutherford classifications are: 0 Asymptomatic; 1 Mild Claudication; 2 Moderate Claudication; 3 Severe Claudication; 4 Ischemic Rest Pain; 5 Minor Tissue Loss; 6 Major Tissue Loss. |
| Clinical Success | At index procedure | Defined as the ability of the FreedomFlow™ Orbital Circumferential Atherectomy System to achieve a final diameter stenosis \<50% immediately post treatment with or without adjunctive therapy, as assessed by an independent Angiographic Core Laboratory. |
| Target Lesion and Vessel Revascularization | 30 days and 6 months | Clinically driven target lesion revascularization (TLR) at 6 months, target vessel revascularization (TVR) at 30 days and 6 months (as assessed by an independent Angiographic Core Laboratory). Clinically driven target lesion revascularization refers to disease progression that is caused by a recurrence of stenosis at the lesion that was treated; target vessel revascularization refers to disease progression that is caused by a recurrence of stenosis in the same vessel as the treated lesion but at a different site. |
| Vessel Patency | 30 days and 6 months | Primary patency, primary assisted patency and secondary patency at 30 days and 6 months. Patency will be evaluated on a per lesion basis by duplex ultrasound and evaluated by an independent Vascular Ultrasound Core Laboratory. Restenosis is defined as Peak Systolic Velocity Rate (PSVR) of 2.5. Patency is determined using ultrasound to measure velocity. Patency is indicated for PSVR values \< 2.5 |
| Vascular Quality of Life Questionnaire (VascuQoL) Administered at Baseline, 30 Days and 6 Months | Baseline, 30 days and 6 months | Patient reported outcomes (PRO, VascuQoL questionnaire) at baseline, 30 days and 6 months. The VascuQoL questionnaire is a validated PRO for lower limb ischemia patients. The range of scores is 1 (worst) to 7 (best) |
| Procedure Success | At index procedure | Defined as \<50% residual stenosis at target lesion with or without adjunctive therapy, no procedure-related MAE, no device malfunction causing the procedure to be aborted. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Interventional Treatment 112 patients had 154 lesions treated | 112 |
| Interventional Treatment 112 patients had 154 lesions treated | 152 |
| Total | 264 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 3 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Patient moved and did not return for follow up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Interventional Treatment |
|---|---|
| Age, Continuous | 70.1 years STANDARD_DEVIATION 9.8 |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African Origin | 16 Participants |
| Race/Ethnicity, Customized Caucasian | 86 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 7 Participants |
| Race/Ethnicity, Customized Native American or Alaskan Native | 1 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants |
| Region of Enrollment United States | 112 participants |
| Rutherford Classification 2 Moderate Claudication | 9 Participants |
| Rutherford Classification 3 Severe Claudication | 55 Participants |
| Rutherford Classification 4 Ischemic Rest Pain | 34 Participants |
| Rutherford Classification 5 Minor Tissue Loss | 14 Participants |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 112 |
| other Total, other adverse events | 71 / 112 |
| serious Total, serious adverse events | 32 / 112 |
Outcome results
Primary
Freedom From Major Adverse Events
Primary safety endpoint is freedom from a composite of new onset major adverse events (MAE) at 30-day follow-up as adjudicated by an Independent Clinical Events Committee. This endpoint is evaluated on a per patient basis.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Site Reported Treatment | Freedom From Major Adverse Events | 104 Participants |
Primary
Technical Success
Defined as the ability of the Cardio Flow FreedomFlow™ Orbital Circumferential Atherectomy System to achieve a residual diameter stenosis ≤50% without adjunctive therapy.
Time frame: At the time of the index procedure, usually within one hour after starting the procedure
Population: 154 distinct lesions in 112 patients were analyzed
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Site Reported Treatment | Technical Success | 144 lesion |
Secondary
Ankle Brachia, Index (ABI) Measured at Baseline, 30 Days and 6 Months
ABI measured at baseline, 30 days and 6 months. ABI ranges from 0 to 1, with smaller values indicating more severe disease. Normal ABI is 1.
Time frame: 30 days and 6 months
Population: Only 107 patients had ABI reported at 30 days and 103 patients had ABI reported at 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Site Reported Treatment | Ankle Brachia, Index (ABI) Measured at Baseline, 30 Days and 6 Months | Baseline ABI | 0.69 units on a scale | Standard Deviation 0.22 |
| Site Reported Treatment | Ankle Brachia, Index (ABI) Measured at Baseline, 30 Days and 6 Months | 30 day ABI | 0.90 units on a scale | Standard Deviation 0.25 |
| Site Reported Treatment | Ankle Brachia, Index (ABI) Measured at Baseline, 30 Days and 6 Months | 6 month ABI | 0.85 units on a scale | Standard Deviation 0.29 |
Secondary
Clinical Success
Defined as the ability of the FreedomFlow™ Orbital Circumferential Atherectomy System to achieve a final diameter stenosis \<50% immediately post treatment with or without adjunctive therapy, as assessed by an independent Angiographic Core Laboratory.
Time frame: At index procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Site Reported Treatment | Clinical Success | 143 lesions |
Secondary
Procedure Success
Defined as \<50% residual stenosis at target lesion with or without adjunctive therapy, no procedure-related MAE, no device malfunction causing the procedure to be aborted.
Time frame: At index procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Site Reported Treatment | Procedure Success | 102 Participants |
Secondary
Rutherford Classification
Change in Rutherford Classification at 30 days and 6 months. Rutherford scale ranges from 0 to 6 with higher values indicating more severe disease. Rutherford classifications are: 0 Asymptomatic; 1 Mild Claudication; 2 Moderate Claudication; 3 Severe Claudication; 4 Ischemic Rest Pain; 5 Minor Tissue Loss; 6 Major Tissue Loss.
Time frame: 30 days and 6 months
Population: Only 107 Patients had reported Rutherford Class at 30 days and only 103 Patients had reported Rutherford Class at 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Site Reported Treatment | Rutherford Classification | Baseline | 3.50 units on a scale | Standard Deviation 0.82 |
| Site Reported Treatment | Rutherford Classification | 30 Days | 1.00 units on a scale | Standard Deviation 1.32 |
| Site Reported Treatment | Rutherford Classification | 6 Months | 0.90 units on a scale | Standard Deviation 1.29 |
Secondary
Target Lesion and Vessel Revascularization
Clinically driven target lesion revascularization (TLR) at 6 months, target vessel revascularization (TVR) at 30 days and 6 months (as assessed by an independent Angiographic Core Laboratory). Clinically driven target lesion revascularization refers to disease progression that is caused by a recurrence of stenosis at the lesion that was treated; target vessel revascularization refers to disease progression that is caused by a recurrence of stenosis in the same vessel as the treated lesion but at a different site.
Time frame: 30 days and 6 months
Population: Onlt 103 patients had TLR reported at 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Site Reported Treatment | Target Lesion and Vessel Revascularization | Freedon From TLR at 30 days | 112 Participants |
| Site Reported Treatment | Target Lesion and Vessel Revascularization | Freedom from TLR at 6 months | 103 Participants |
Secondary
Vascular Quality of Life Questionnaire (VascuQoL) Administered at Baseline, 30 Days and 6 Months
Patient reported outcomes (PRO, VascuQoL questionnaire) at baseline, 30 days and 6 months. The VascuQoL questionnaire is a validated PRO for lower limb ischemia patients. The range of scores is 1 (worst) to 7 (best)
Time frame: Baseline, 30 days and 6 months
Population: Only 107 patients had reported VascuQoL at 30 days and only 103 patients had reported VascuQoL at 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Site Reported Treatment | Vascular Quality of Life Questionnaire (VascuQoL) Administered at Baseline, 30 Days and 6 Months | Baseline VascuQoL | 3.96 units on a scale | Standard Deviation 1.42 |
| Site Reported Treatment | Vascular Quality of Life Questionnaire (VascuQoL) Administered at Baseline, 30 Days and 6 Months | 30 day VascuQoL | 5.33 units on a scale | Standard Deviation 1.27 |
| Site Reported Treatment | Vascular Quality of Life Questionnaire (VascuQoL) Administered at Baseline, 30 Days and 6 Months | 6 month VascuQoL | 5.32 units on a scale | Standard Deviation 1.3 |
Secondary
Vessel Patency
Primary patency, primary assisted patency and secondary patency at 30 days and 6 months. Patency will be evaluated on a per lesion basis by duplex ultrasound and evaluated by an independent Vascular Ultrasound Core Laboratory. Restenosis is defined as Peak Systolic Velocity Rate (PSVR) of 2.5. Patency is determined using ultrasound to measure velocity. Patency is indicated for PSVR values \< 2.5
Time frame: 30 days and 6 months
Population: Only 129 lesions had patency reported at 30 days and only 121 lesions had patency reported at 6 months
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Site Reported Treatment | Vessel Patency | Primary Patency at 30 days | 123 lesion |
| Site Reported Treatment | Vessel Patency | Primary Patency at 6 months | 86 lesion |
| Primary Assisted Patency | Vessel Patency | Primary Patency at 30 days | 128 lesion |
| Primary Assisted Patency | Vessel Patency | Primary Patency at 6 months | 113 lesion |