Investigational Device Exemption Study to Determine the Safety and Efficacy of the Astron and Pulsar Stents

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to separately demonstrate the safety and efficacy of BIOTRONIK's Astron and Pulsar stents. The Pulsar stent will be used for the treatment of femoro-popliteal lesions, located in the native superficial femoral artery (SFA) or proximal popliteal artery (PPA), while the Astron stent will be used for the treatment of the common or external iliac artery lesions.

Official Title
-----------------
The Treatment of Iliac and Femoral Atherosclerotic Lesions Using the Self-expanding Astron and Pulsar Stents

Conditions
-----------------
Peripheral Vascular Disease, Peripheral Artery Disease

Intervention / Treatment
-----------------
* Device: Astron Stents
* Device: Pulsar Stents


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria To support the objectives of this study, the following initial inclusion criteria must be met for a subject to be enrolled and considered for the index procedure: Age ≥ 18 years Willingness to comply with study follow-up requirements Candidate for PTA Life-style limiting claudication or rest pain with an ABI ≤ 0.9 (resting or exercise). Thigh brachial index (TBI) may be used / performed if ABI is inadequate. Written informed consent For a subject to receive an investigational stent, the following procedure-related criteria must be met: One de novo, restenotic or occluded lesion representing a femoro-popliteal or iliac indication OR Two de novo, restenotic or occluded lesions representing one femoro-popliteal indication and one iliac indication on contralateral limbs - (i.e. one lesion per limb) Lesions may be one solid lesion or a series of multiple, smaller lesions to be treated as one lesion Subjects with bilateral, SFA/PPA disease (i.e. one SFA/PPA lesion per limb) are eligible for enrollment into the study. The target lesion will be selected at the investigator's discretion based on study eligibility criteria. The contralateral SFA/PPA intervention may be performed at the time of the index procedure (prior to treatment of study lesion); however, the use of an investigational treatment is prohibited. If the contralateral SFA/PPA intervention is not performed at the time of the index procedure, the intervention must be performed at least 30 days after the index procedure. The use of an investigational treatment for the contralateral intervention is prohibited. Subjects with bilateral, iliac disease (i.e. one iliac lesion per limb) are eligible for enrollment into the study. The target lesion will be selected at the investigator's discretion based on study eligibility criteria. The contralateral iliac intervention may be performed at the time of the index procedure; however, the use of an investigational treatment is prohibited. If the contralateral iliac intervention is not performed at the time of the index procedure, the intervention must be performed at least 30 days after the index procedure. The use of an investigational treatment for the subsequent contralateral intervention is also prohibited. Femoro-popliteal lesions must be located at least 1 cm distal to the profunda femoris artery and at least 3 cm above the knee joint (radiographic joint space) Iliac lesions must be located only in either the common or external iliac artery Lesions must be treatable with a maximum of two stents Angiographic evidence of ≥ 70% stenosis or occlusion (operator visual assessment) Lesion length ≤ 190 mm (if de novo or restenotic) or ≤ 100 mm (if occluded) Target vessel reference diameter: 2.5 to 6 mm (SFA/PPA) or 6 to 9 mm (iliac arteries) by visual estimate Angiographic evidence of patent SFA and PPA (iliac indication) and angiographic evidence of at least one distal vessel runoff to the foot (both femoro-popliteal and iliac indications). Patent is defined as < 50% stenosis. For SFA/PPA intervention, a significant stenosis (> 70%) or occlusion of an ipsilateral, inflow artery (e.g. aortoiliac, common femoral) must be successfully treated (use of investigational treatment prohibited) just prior to treatment of the target lesion. Successful treatment is defined as no complications and less than 30% residual stenosis following intervention. Exclusion Criteria To support the objectives of this study, the following initial exclusion criteria must not be present for a subject to be enrolled: Subjects pregnant or planning to become pregnant during the course of the study Life expectancy of less than one year Rutherford-Becker category 5 or 6. Subjects with ulcers caused by venous disease may be enrolled in the study. Previously stented lesion(s) in the target vessel Target lesion(s) received previous treatment within 30 days prior to enrollment Prior peripheral vascular bypass surgery involving the target limb(s) Thrombophlebitis or deep vein thrombosis within the past 30 days Known allergy to nitinol (nickel and/or titanium) Participation in any other clinical investigational device or drug study. Subjects may be concurrently enrolled in a post-market study, as long as the post-market study device, drug or protocol does not interfere with the investigational treatment or protocol of this study. Previous stroke or transient ischemic attack within the last three months prior to enrollment Previous coronary or peripheral bypass surgery (non-target limb) within 30 days prior to enrollment Intolerance to contrast agents that cannot be medically managed and/or intolerance to anti-platelet, anti-coagulant or thrombolytic medications Refuses blood transfusions Any medical condition, that in the opinion of the investigator, poses an unacceptable risk for implant of a stent according to the study indications For a subject to receive an investigational stent the following procedure-related criteria must not be present: INR ≥ 1.6 Concomitant renal failure with serum creatinine level > 2.5 mg/dL Unresolved neutropenia (white blood cell count < 3,000 / µL) or thrombocytopenia (platelet count < 80,000 / µL) at the time of the index procedure Unresolved bleeding disorder (INR ≥ 1.6) at the time of the index procedure Presence of other ipsilateral, arterial lesions distal to the target lesion requiring treatment within 30 days of the index procedure (either before or after) or at the time of the index procedure Additional percutaneous interventional procedures (cardiac and/or peripheral) planned within 30 days after the index procedure Presence of a complication following pre-dilation of target lesion Presence of a target vessel/lesion that is excessively tortuous or calcified or is adjacent to an acute thrombus that is unresponsive to anti-thrombotic therapies Target lesion is located within an aneurysm or associated with an aneurysm in the vessel segment either proximal or distal to the target lesion Target lesion requires the use of cutting balloons, atherectomy or ablative devices Subjects with less than single vessel runoff to the foot

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Astron Stent Group<br>Participants indicated for stenting in iliac atherosclerotic lesions. Intervention: Device: Astron Stents | Device: Astron Stents<br>* Implantation of self-expanding, bare-metal, nitinol stents for treatment of peripheral artery disease affecting the iliac artery.<br>* Other names: Astron Stent;|
| Experimental: Pulsar Stent Group<br>Participants indicated for stenting in superficial femoral or proximal popliteal atherosclerotic lesions. Intervention: Device: Pulsar Stents | Device: Pulsar Stents<br>* Implantation of self-expanding, bare-metal, nitinol stents for treatment of peripheral artery disease affecting superficial femoral or proximal popliteal arteries.<br>* Other names: Pulsar Stent;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness Endpoint for the Pulsar Stent: Primary Patency | The primary effectiveness endpoint for the Pulsar stent group is the primary patency rate at 12 months post-index procedure. Primary patency is defined as freedom from more than 50% restenosis based on the duplex ultrasound peak systolic velocity ratio, comparing data within the treated segment to the proximal normal segment or based on a clinically-indicated TLR with angiographic evidence of > 50% stenosis. | 12 months | 
| Safety Endpoint for the Pulsar Stent: Freedom From Procedure- or Stent-related Major Adverse Events | The primary safety endpoint for the Pulsar stent is the freedom from procedure- or stent-related major adverse events at 30 days post-index procedure. The major adverse event rate includes mortality, target lesion revascularization and index limb amputation. | 30 days | 
| Safety and Effectiveness Endpoint for the Astron Stent - Percentage of Participants With Major Adverse Events (MAE) | The primary endpoint for the Astron stent is a composite of the rate of procedure- or stent-related major adverse events at 12 months post-index procedure. The major adverse event rate includes 30-day mortality, along with 12-month rates of target lesion revascularization and index limb amputation. Success was measured against a performance goal of 15%, given a 7.5% expected 12-month MAE rate, with an assumed delta value of 7.5%. | 12 months | 
| Percentage of Participants With Primary Safety Endpoint (Post Market Analysis) | Freedom from a composite of clinically-driven target lesion revascularization (TLR) and index limb amputation at 36 months. | 36 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Safety Assessment for the Pulsar Stent: Individual Rates of Mortality, TLR, and Index Limb Amputation | Evaluate the contribution of the individual rates of mortality, target lesion revascularization (TLR) and index limb amputation at 30 days post-index procedure to the primary safety endpoint for the Pulsar stent. | 30 days | 
| Long-Term Safety Assessment for the Pulsar Stent: Major Adverse Event Rate | Evaluate the long-term major adverse event rate of the Pulsar stent. Likewise, the endpoint will evaluate the contribution of the individual rates of 30-day mortality and 12-month target lesion revascularization and index limb amputation rates to this overall, long-term major adverse event rate. | 12 months | 
| Stent Integrity Assessment for the Pulsar Stent: Stent Fracture Rate | Evaluate the Pulsar stent integrity as measured by x-ray at 12 months post-index procedure. An independent angiographic core laboratory reviewed x-ray imaging for presence or absence of a stent fracture. Fractures were assessed with Grade I indicating a single tine fracture, Grade II indicating multiple tine fracture, Grade III indicating stent fracture(s) with preserved alignment of the components, Grade IV indicating stent fracture(s) with mal-alignment of the components, and Grade V stent fracture(s) in a trans-axial spiral configuration. Generally, fractures of Grade I are least severe, increasing in severity to Grade V. | 12 months | 
| Secondary Safety Assessment for the Astron Stent - Distribution of MAE Rate | Evaluate the contribution of the individual rates of 30-day mortality and 12-month target lesion revascularization and index limb amputation rates to the primary endpoint for the Astron stent. | 12 months | 
| Secondary Effectiveness Assessment for the Astron Stent - Primary Patency Rate | Evaluate the primary patency of the Astron stent at 12 months post-index procedure as measured by duplex ultrasound. Primary patency is defined as freedom from more than 50% restenosis based on the duplex ultrasound peak systolic velocity ratio, comparing data within the treated segment to the proximal normal segment or based on a clinically-indicated TLR with angiographic evidence of > 50% stenosis. | 12 months | 
| Secondary Effectiveness Assessment for the Astron and Pulsar Stents - Primary Assisted Patency | Evaluate the primary assisted patency rate (freedom from remote Target Vessel Revascularization [TVR]) for the Astron and Pulsar stent at 12 months post-index procedure. | 12 months | 
| Secondary Effectiveness Assessment for the Astron and Pulsar Stents - Secondary Patency | Evaluate the secondary patency rate (freedom from bypass and amputation of the target limb) for the Astron and Pulsar stent at 12 months post-index procedure. | 12 months | 
| Functional Assessments for Subjects With the Astron and Pulsar Stents - Ankle - Brachial Index (ABI) Measurement | The purpose of this endpoint is to compare the ABI measurements between baseline and 12 months post-index procedure. ABI is the ratio of systolic blood pressure of ankle relative to systolic blood pressure of arm. | 12 months | 
| Functional Assessments for Subjects With the Astron and Pulsar Stents - Six-Minute Walk Test | The purpose of this endpoint is to compare the distance walked during the 6-minute walk test between baseline and 12 months post-index procedure. | 12 months | 
| Functional Assessments for Subjects With the Astron and Pulsar Stents - Walking Impairment Questionnaire PAD Specific Score | The purpose of this endpoint is to compare Walking Impairment Questionnaire (WIQ) Peripheral Arterial Disease (PAD) specific score between baseline and 12 months post-index procedure. The WIQ is a subjective questionnaire completed by participants at baseline and the 12 month visit which asks questions about mobility to assess walking impairment. Larger numbers indicate better outcomes, with a minimum score of 0 and a maximum score of 100. Please see the following publication for further information: Hiatt WR, Hirsch AT, Regensteiner JG, et al. Clinical Trials for Claudication. Assessment of Exercise Performance, Functional Status, and Clinical Endpoints. Vascular Clinical Trialists. Circulation. 1995;92:614-621 | 12 months | 
| Functional Assessments for Subjects With the Astron and Pulsar Stents - Walking Impairment Questionnaire Walking Distance Score | The purpose of this endpoint is to compare Walking Impairment Questionnaire Walking Distance score between baseline and 12 months post-index procedure. The WIQ is a subjective questionnaire completed by participants at baseline and the 12 month visit which asks questions about mobility to assess walking impairment. Larger numbers indicate better outcomes, with a minimum score of 0 and a maximum score of 100.. Please see the following publication for further information: Hiatt WR, Hirsch AT, Regensteiner JG, et al. Clinical Trials for Claudication. Assessment of Exercise Performance, Functional Status, and Clinical Endpoints. Vascular Clinical Trialists. Circulation. 1995;92:614-621 | 12 months | 
| Functional Assessments for Subjects With the Astron and Pulsar Stents - Walking Impairment Questionnaire Walking Speed Score | The purpose of this endpoint is to compare Walking Impairment Questionnaire Walking Speed score between baseline and 12 months post-index procedure. The WIQ is a subjective questionnaire completed by participants at baseline and the 12 month visit which asks questions about mobility to assess walking impairment. Larger numbers indicate better outcomes, with a minimum score of 0 and a maximum score of 100.. Please see the following publication for further information: Hiatt WR, Hirsch AT, Regensteiner JG, et al. Clinical Trials for Claudication. Assessment of Exercise Performance, Functional Status, and Clinical Endpoints. Vascular Clinical Trialists. Circulation. 1995;92:614-621 | 12 months | 
| Functional Assessments for Subjects With the Astron and Pulsar Stents - Walking Impairment Questionnaire Stair Climbing Score | The purpose of this endpoint is to compare Walking Impairment Questionnaire Stair Climbing score between baseline and 12 months post-index procedure. The WIQ is a subjective questionnaire completed by participants at baseline and the 12 month visit which asks questions about mobility to assess walking impairment. Larger numbers indicate better outcomes, with a minimum score of 0 and a maximum score of 100. Please see the following publication for further information: Hiatt WR, Hirsch AT, Regensteiner JG, et al. Clinical Trials for Claudication. Assessment of Exercise Performance, Functional Status, and Clinical Endpoints. Vascular Clinical Trialists. Circulation. 1995;92:614-621 | 12 months | 
| Acute Procedural Success for Astron and Pulsar Stent | Evaluate the acute procedural success of the Astron and Pulsar stent. Acute procedural success is defined as completion of the assigned procedure, the stented lesion having less than 30% residual stenosis determined by angiography immediately after stent placement and no MAEs before hospital discharge. | 30 days | 
| Clinical Success | Evaluate the 30-day clinical success of the procedure. The 30-day clinical success is defined as completion of the assigned procedure, the stented lesion having less than 30% residual stenosis determined by angiography immediately after stent placement and no MAEs within 30 days of the index procedure. | 30 days | 
| Secondary Safety Assessment for Astron and Pulsar Stent: Adverse Event Rates | Evaluate the rates of all individual adverse event types that are not included in the primary endpoint analyses for the Astron stent and the Pulsar stent group. Please see the Serious Adverse Events and Other Adverse Events sections for event details. | 12 month | 
| Comparison of Endpoints Results Between Occlusive and Non-occlusive Lesions for Astron and Pulsar Stent - 30 Day MAE Rate | Compare the 30 day MAE rate results between evaluable subjects treated for occlusive lesions (100% stenosis) and evaluable subjects treated for non-occlusive lesions (70% - 99% stenosis) for the Astron stent and the Pulsar stent group. | 30 days | 
| Comparison of Endpoints Results Between Occlusive and Non-occlusive Lesions for Astron and Pulsar Stent - Primary Patency at 12-months | Compare the primary patency at 12-months results between evaluable subjects treated for occlusive lesions (100% stenosis) and evaluable subjects treated for non-occlusive lesions (70% - 99% stenosis) for the Astron stent and the Pulsar stent group. | 12 months | 
| Comparison of Endpoints Results Between Occlusive and Non-occlusive Lesions for Astron and Pulsar Stent - Primary Assisted Patency at 12-Months | Compare the primary assisted patency (freedom from remote TVR) at 12-months results between evaluable subjects treated for occlusive lesions (100% stenosis) and evaluable subjects treated for non-occlusive lesions (70% - 99% stenosis) for the Astron stent and the Pulsar stent group. | 12 months | 
| Comparison of Endpoints Results Between Occlusive and Non-occlusive Lesions for Astron and Pulsar Stent - Secondary Patency Rate at 12-Months | Compare the secondary patency (freedom from bypass and amputation of the target limb) at 12-months results between evaluable subjects treated for occlusive lesions (100% stenosis) and evaluable subjects treated for non-occlusive lesions (70% - 99% stenosis) for the Astron stent and the Pulsar stent group. | 12 months | 
| Comparison of Endpoints Results Between Occlusive and Non-occlusive Lesions for Astron and Pulsar Stent - Acute Procedure Success | Compare the acute procedure success results between evaluable subjects treated for occlusive lesions (100% stenosis) and evaluable subjects treated for non-occlusive lesions (70% - 99% stenosis) for the Astron stent and the Pulsar stent group. | Acute / Date of Procedure | 
| Comparison of Endpoints Results Between Occlusive and Non-occlusive Lesions for Astron and Pulsar Stent - 30-Day Clinical Success | Compare the 30-day clinical success results between evaluable subjects treated for occlusive lesions (100% stenosis) and evaluable subjects treated for non-occlusive lesions (70% - 99% stenosis) for the Astron stent and the Pulsar stent group. | 30 days | 
| Comparison of Endpoint Results Between Standard and Long Lesions for the Pulsar Stent - MAE Rate | Compare the MAE rate results between evaluable subjects treated with standard length lesions (between 20 mm and 140 mm) and evaluable subjects treated for long lesions (between 141 mm and 190 mm) for the Pulsar stent group. | 12 months | 
| Comparison of Endpoint Results Between Standard and Long Lesions for the Pulsar Stent - Primary Patency at 12 Months | Compare the primary patency rate at 12 months between evaluable subjects treated with standard length lesions (between 20 mm and 140 mm) and evaluable subjects treated for long lesions (between 141 mm and 190 mm) for the Pulsar stent group. | 12 months | 
| Comparison of Endpoint Results Between Standard and Long Lesions for the Pulsar Stent - Stent Fracture Rate at 12 Months | Compare the stent fracture rate at 12 months between evaluable subjects treated with standard length lesions (between 20 mm and 140 mm) and evaluable subjects treated for long lesions (between 141 mm and 190 mm) for the Pulsar stent group. | 12 months | 
| Comparison of Endpoint Results Between Standard and Long Lesions for the Pulsar Stent - Primary Assisted Patency at 12 Months | Compare the primary assisted patency rate at 12 months between evaluable subjects treated with standard length lesions (between 20 mm and 140 mm) and evaluable subjects treated for long lesions (between 141 mm and 190 mm) for the Pulsar stent group. | 12 months | 
| Comparison of Endpoint Results Between Standard and Long Lesions for the Pulsar Stent - Secondary Patency Rate at 12 Months | Compare the secondary patency rate at 12 months between evaluable subjects treated with standard length lesions (between 20 mm and 140 mm) and evaluable subjects treated for long lesions (between 141 mm and 190 mm) for the Pulsar stent group. | 12 months | 
| Comparison of Endpoint Results Between Standard and Long Lesions for the Pulsar Stent - Acute Procedure Success | Compare the acute procedure success results between evaluable subjects treated with standard length lesions (between 20 mm and 140 mm) and evaluable subjects treated for long lesions (between 141 mm and 190 mm) for the Pulsar stent group. | Acute / Date of Procedure | 
| Comparison of Endpoint Results Between Standard and Long Lesions for the Pulsar Stent - 30-day Clinical Success | Compare the 30-day clinical success results between evaluable subjects treated with standard length lesions (between 20 mm and 140 mm) and evaluable subjects treated for long lesions (between 141 mm and 190 mm) for the Pulsar stent group. | 30 days | 
| Number of Participants With Freedom From Clinically-driven TLR and Index Limb Amputation at 24 Months (Post Approval) | Evaluate the rate of freedom from target lesion revascularization (TLR) and/or index limb amputation for the Pulsar stent. | 24 Months | 
| Safety Assessment for the Pulsar Stent: Percentage of Participants With Mortality, TLR, and Index Limb Amputation (Post Approval) | Evaluate the contribution of the individual rates of mortality, target lesion revascularization (TLR) and index limb amputation at 30 days post-index procedure to the primary safety endpoint for the Pulsar stent. | 24 Months | 
| Percentage of Participants for the Pulsar Stent Group With MAE (30-day Mortality, Clinically-driven TLR, and Index Limb Amputation) and Their Components at 36 Months (Post Approval). | Evaluate the MAE rate and the individual component rates of mortality at 30 days post-index procedure, target lesion revascularization (TLR) and index limb amputation for the Pulsar stent. | 36 Months | 
| Percentage of Participants With Target Lesion Revascularization (TLR) at 24 Months (Post Approval) (Pulsar Stent Group) |  | 24 Months | 
| Percentage of Participants With Target Lesion Revascularization (TLR) at 36 Months (Post Approval) (Pulsar Stent Group) |  | 36 Months | 
| Number of Participants With Stent Fracture at 24 Months (Post Approval). |  | 24 Months | 
| Number of Participants With Stent Fracture at 36 Months (Post Approval) (Pulsar Stent Group). |  | 36 Months | 
| Percentage of Subjects With Serious Adverse Events at 36 Months (Post Approval) (Pulsar Stent Group). | Summary of serious adverse event rates at 36 months. Refer to SAE section. | 36 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vascular intervention, Endovascular, Peripheral stent