The THOR IDE Study

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical trial is to test the Thor system in adult (≥ 18 year old) patients with de novo (new, never treated) calcified lesions in infrainguinal (leg) arteries (peripheral artery disease or PAD). The main question[s] it aims to answer are: Is the Thor system safe in treating these lesions Does the Thor system work to treat these lesions Participants will: Receive treatment with the Thor system Have follow-up visits at Discharge, 30 days, 6 months, and 12 months

Detailed Description
-----------------
Up to 30 sites in the U.S. will be selected to do this study. Patients with pain in their legs when walking and/or resting that is due to lack of blood flow to their legs may be able to join the study. To join the study patients must also have blockages in their leg arteries that meet the study criteria. Before the Thor procedure, patients will have a screening visit that includes a review of their medical records, questions about their medical history and medications taken for blood thinning or circulation, a physical examination of their legs, a test to check the blood flow in their legs (by checking arm and leg blood pressures), blood tests, and a pregnancy test if they are a female able to have children. Patients will also answer questions about any trouble they have had with walking in the last week and their overall quality of life. All patients in the study will have treatment with the Thor system. There is no control group (a group of patients that receives only standard treatment or receives no treatment at all) in this study. During the procedure, the doctor will take x-ray pictures of the leg arteries. They may also use other treatments such as angioplasty balloons, drug-coated balloons, stents, and filters that collect blood clots, if needed. Patients treated with the Thor system will be watched until they are ready to go home or up to 24 hours after the procedure if they do not go home right away. Before they go home they will have a test to check the blood flow to their legs (by checking arm and leg blood pressures) and be checked for any adverse events. Patients will return for visits at 30 days, 6 months, and 12 months after the Thor procedure. At these visits patients will be asked questions about their medical history and medications taken for blood thinning or circulation, have a physical examination of their legs, have a test to check the blood flow in their treated leg (by checking arm and leg blood pressures), have an ultrasound of their treated leg, and be checked for any adverse events. Patients will also answer questions about any trouble they have had with walking in the last week and their overall quality of life. It will take up to 24 months (2 years) to enroll all of the patients in the study. Patients who join the study will be in the study for about 12 months (1 year) and will have all of the visits with their doctor that they would normally have for their PAD.

Official Title
-----------------
The THOR IDE Study

Conditions
-----------------
Peripheral Artery Disease, Peripheral Artery Stenosis, Peripheral Artery Calcification, PAD

Intervention / Treatment
-----------------
* Device: Thor laser atherectomy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient age is ≥18 years Patient agrees to participate and to comply with the protocol by signing an IRB approved patient consent form Patient is able to walk unassisted or with non-motorized assistive devices Patient has PAD with documented Rutherford Class 2-4 of the target limb Life expectancy >12 months Angiographic Inclusion Criteria: Patient has de novo atherosclerotic disease of the native SFA and/or the femoropopliteal arteries Target lesion has ≥70% diameter stenosis by investigator via visual assessment Target lesion length ≤150mm. Multiple lesions that are within a 150mm segment will be treated and assessed as a single lesion Chronic total occlusion lesion length is <100mm of the total ≤150mm target lesion Minimum reference vessel diameter (RVD) 4.0mm by visual estimate Target lesion crossed and intraluminal guidewire placement confirmed; successful crossing defined as tip of the guidewire distal to the target lesion in the absence of flow limiting dissections or perforations At least one patent tibial vessel (defined as <50% stenosis) with runoff to the foot Target lesion has moderate to severe calcification graded using the Peripheral Academic Research Consortium (PARC) criteria Exclusion Criteria: Subject has active infection requiring antibiotic therapy Stenting planned within the target lesion Known positive for COVID-19 within the last 2 weeks and actively symptomatic Pregnant (positive pregnancy test) or currently breast feeding Evidence of Acute Limb Ischemia within 7 days prior to procedure Cerebrovascular accident (CVA) <60 days prior to procedure Myocardial infarction <60 days prior to procedure History of unstable coronary artery disease or other uncontrollable comorbidity resulting in hospitalization within the last 60 days prior to enrollment Known contraindication to aspirin, antiplatelet/anti-coagulant therapies required for procedure/follow-up Known allergy to contrast media that cannot adequately be premedicated prior to study procedure History of Thrombophilia, Heparin-induced Thrombocytopenia (HIT), or Heparin-induced Thrombotic Thrombocytopenia Syndrome (HITTS) Serum creatinine ≥2.5mg/dL (unless dialysis-dependent) tested within a week prior to procedure Planned lower limb major amputation (above the ankle) Other surgical or endovascular procedure in the target limb that occurred within 14 days prior to index procedure or is planned for within 30 days following index procedure, with the exception of diagnostic angiography Currently participating in any investigational device or drug clinical trial that, in the opinion of the investigator, will interfere with the conduct of the current trial The use of specialty balloons, re-entry or additional atherectomy devices Angiographic Exclusion Criteria: Subject has significant stenosis (>50% stenosis) or occlusion of inflow tract before target treatment zone (e.g. iliac or common femoral) not successfully treated

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
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective, single-arm, multicenter, and open-label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thor Treatment<br>Treatment with the Thor system | Device: Thor laser atherectomy<br>* Treatment of de novo calcified lesions with laser atherectomy and calcium modification using the Thor system<br>* Other names: Thor calcium modification;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from Major Adverse Events (MAEs) | Defined as freedom from MAEs including all-cause mortality, clinically driven target lesion revascularization (CD-TLR), unplanned target limb major amputation, and peri-procedural perforations, flow-limiting dissections, and symptomatic distal embolizations that require an intervention to resolve | 30 Days | 
| Procedural Success | Defined as residual diameter stenosis ≤50% as determined by angiographic core lab | At completion of the procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target lesion patency, 30 days | Defined as freedom from CD-TLR and freedom from ≥50% restenosis as determined by duplex ultrasound (DUS) | 30 days | 
| Target lesion patency, 6 months | Defined as freedom from CD-TLR and freedom from ≥50% restenosis as determined by duplex ultrasound (DUS) | 6 months | 
| Target lesion patency, 12 months | Defined as freedom from CD-TLR and freedom from ≥50% restenosis as determined by duplex ultrasound (DUS) | 12 months | 
| Clinically-driven target lesion revascularization | Defined as repeat revascularization procedure of the target lesion if PSVR is ≥2.5 by DUS or if angiography shows a percent diameter stenosis >50% and there are worsening clinical symptoms, worsening Rutherford Clinical Category or ABI that is clearly referable to the target lesion. | Through 12 months | 
| Technical success | Defined as the ability to deliver the Thor system and achieve residual diameter stenosis ≤50% after treatment with Thor and prior to adjunctive PTA, as confirmed by independent core laboratory assessments of angiographic images | Peri-procedural | 
| Frequency of peri-procedural adverse events | Defined as frequency of adverse events related to the investigational device (Thor system) | Within 24 hours of the procedure | 
| Adjunctive devices used with the Thor system | Defined as the use of other devices including angioplasty balloons, drug coated balloons, stents, embolic filters | Peri-procedural | 
| Ankle-Brachial Index (ABI) change, Discharge | Defined as the change in blood pressure in the upper limb (arm) and lower limb (leg or toes) at discharge compared to the baseline (Screening) value | Discharge or up to 24 hours after the procedure | 
| Ankle-Brachial Index (ABI) change, 30 days | Defined as the change in blood pressure in the upper limb (arm) and lower limb (leg or toes) at 30 days compared to the baseline (Screening) value | 30 days | 
| Ankle-Brachial Index (ABI) change, 6 months | Defined as the change in blood pressure in the upper limb (arm) and lower limb (leg or toes) at 6 months compared to the baseline (Screening) value | 6 months | 
| Ankle-Brachial Index (ABI) change, 12 months | Defined as the change in blood pressure in the upper limb (arm) and lower limb (leg or toes) at 12 months compared to the baseline (Screening) value | 12 months | 
| Rutherford Classification change, 30 days | Defined as the change in Rutherford classification at 30 days compared to the baseline (Screening) value. Rutherford Classification is a staging system to describe reduced blood flow in the lower limb. Rutherford Classifications values range from the least severe (asymptomatic) which is scored a 0 to the most severe (ulceration or gangrene) which is scored a 6. | 30 days | 
| Rutherford Classification change, 6 months | Defined as the change in Rutherford classification at 6 months compared to the baseline (Screening) value. Rutherford Classification is a staging system to describe reduced blood flow in the lower limb. Rutherford Classifications values range from the least severe (asymptomatic) which is scored a 0 to the most severe (ulceration or gangrene) which is scored a 6. | 6 months | 
| Rutherford Classification change, 12 months | Defined as the change in Rutherford classification at 12 months compared to the baseline (Screening) value. Rutherford Classification is a staging system to describe reduced blood flow in the lower limb. Rutherford Classifications values range from the least severe (asymptomatic) which is scored a 0 to the most severe (ulceration or gangrene) which is scored a 6. | 12 months | 
| Freedom from Major Adverse Events (MAEs) | Defined as freedom from MAEs including all-cause mortality, clinically driven target lesion revascularization (CD-TLR), unplanned target limb major amputation, and peri-procedural perforations, flow-limiting dissections, and symptomatic distal embolizations that require an intervention to resolve | Through 12 months | 
| Change in Short Form Health Survey (SF-36) score, 30 days | Defined as the change in SF-36 score at 30 days compared to the baseline (Screening) value. The SF-36 is a patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | 30 days | 
| Change in Short Form Health Survey (SF-36) score, 6 months | Defined as the change in SF-36 score at 6 months compared to the baseline (Screening) value. The SF-36 is a patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | 6 months | 
| Change in Short Form Health Survey (SF-36) score, 12 months | Defined as the change in SF-36 score at 12 months compared to the baseline (Screening) value. The SF-36 is a patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. | 12 months | 
| Change in Walking Impairment Questionnaire (WIQ) score, 30 days | Defined as the change in WIQ score at 30 days compared to the baseline (Screening) value. The WIQ measures self-reported walking impairment, walking distance, walking speed, and stair-climbing ability. In the WIQ there are 21 questions to rate the degree of difficulty with the walking and stair climbing elements. The response for each question is on a 0 to 4 scale, where 0 represents the inability to walk or climb stairs, and 4 represents no difficulty. | 30 days | 
| Change in Walking Impairment Questionnaire (WIQ) score, 6 months | Defined as the change in WIQ score at 6 months compared to the baseline (Screening) value. The WIQ measures self-reported walking impairment, walking distance, walking speed, and stair-climbing ability. In the WIQ there are 21 questions to rate the degree of difficulty with the walking and stair climbing elements. The response for each question is on a 0 to 4 scale, where 0 represents the inability to walk or climb stairs, and 4 represents no difficulty. | 6 months | 
| Change in Walking Impairment Questionnaire (WIQ) score, 12 months | Defined as the change in WIQ score at 12 months compared to the baseline (Screening) value. The WIQ measures self-reported walking impairment, walking distance, walking speed, and stair-climbing ability. In the WIQ there are 21 questions to rate the degree of difficulty with the walking and stair climbing elements. The response for each question is on a 0 to 4 scale, where 0 represents the inability to walk or climb stairs, and 4 represents no difficulty. | 12 months |