IV-X Medical First-in-Human Peripheral Intravascular Lithotripsy Study for PAD

IV-X Medical is conducting a prospective, single-arm, single-center clinical premarket study to evaluate the safety and effectiveness of the IV-X Medical IVL System to treat moderately to severely calcified peripheral arteries in the iliac, femoral, ilio-femoral, popliteal, and infra-popliteal arteries. Up to 25 subjects will be enrolled.

• IV-X Medical IVL System (Device): The IV-X Medical Intravascular Lithotripsy (IVL) System (IV-X IVL System) is a balloon-based lithotripsy device designed to treat calcified peripheral artery lesions. The device employs sonic pressure waves to fracture the calcifications, restoring blood flow and improving vascular health.

Primary outcomes

• Primary Safety Endpoint defined as proportion of subjects with one or more new onset Major Adverse Events (MAEs) through 30 days post-procedure. [30 Days]: Major Adverse Events (MAEs) are defined as: * Clinically driven target limb revascularization * Unplanned amputation of the target limb above the ankle * Device- or procedure-related post-operative death
• Primary Effectiveness Endpoint defined as the number of subjects with post-procedure residual diameter stenosis of <50% (after adjunctive therapy, if used), as assessed by quantitative angiography. [Day of procedure]

Secondary outcomes

• Secondary Endpoint of Acute Procedural Success with Freedom from Procedural Major Adverse Events. [Day of Procedure]: Defined as the number of patients with BOTH post-procedure residual diameter stenosis of <50% (without adjunctive therapy and/or stenting, if used) as assessed by Investigator via visual estimate and freedom from procedural major adverse events.
• Secondary Endpoint of Acute Procedural Success defined as number of procedures with successful IVL treatment delivery in desired location using 2 or fewer catheters. [Day of Procedure]
• Secondary Safety Endpoint defined as the proportion of subjects with one or more device- or procedure-related adverse events (AEs) or serious adverse events (SAEs) through 30 days post-procedure. [30 Days]
• Secondary Safety Endpoint defined as freedom from clinically driven target lesion revascularization (TLR-lesion) at 30 days. [30 Days]
• Change in Rutherford Clinical Category score at 30 days, compared to Baseline. [30 Days]
• Secondary Endpoint for Treatment Effectiveness defines as number of patients with target lesion patency - freedom from ≥50% restenosis at 30 days post-procedure (vessel is patent and duplex ultrasound peak systolic velocity ratio ≥2.4). [30 Days]
• Change in ankle-Brachial Index (ABI) and/or toe-Brachial Index (TBI) of the target limb at 30 days, compared to Baseline. [30 Days]
• Secondary Endpoint of Procedural Success defined as the number of procedures with successful crossing of below-the-knee (BTK) lesions without adjunctive pre-dilation. [Day of Procedure]

Sex: All, ages: 18 Years to any

Eligibility criteria are differentiated, where appropriate, by lesion location of above-the-knee (ATK) or below-the-knee (BTK).

Standard Inclusion Criteria:

1. Age of subject is >18.
2. Rutherford Clinical Category:

   1. ATK: 2, 3, or 4
   2. BTK: 4 or 5 (Category 5 will only include patients with ulcers not extending proximal to the metatarsal head)
3. Estimated life expectancy >1 year in the opinion of the investigator at the time of enrollment.
4. Subject or subject's legal representative agrees to participate and comply with the study assessments.

Angiographic Inclusion Criteria:

1. Subject is a suitable candidate for angiography and endovascular intervention, in the opinion of the investigator or per hospital guideline.
2. De novo target lesion that is located in a native vessel as follows:

   1. ATK: Iliac, superficial femoral artery (SFA), popliteal artery (extends to 2cm above the bifurcation or trifurcation of the tibial artery)
   2. BTK: distal segment (P3) of the popliteal artery to the ankle joint
3. Target lesion reference vessel diameter is between the following sizes by visual estimate:

   1. ATK: 3.5mm and 12.0mm
   2. BTK: 2.0mm and 5.0mm
4. Target lesion stenosis ≥70% via visual estimate.
5. Subject has at least:

   1. ATK: One (1) patent contiguous vessel with runoff to the foot (not supported by collateral circulation) in the target leg. Vessel patency is defined as no stenosis >50%.
   2. BTK: Distal constitution of one (1) pedal vessel (< 50% stenosis) (desert foot excluded).
6. Ability to pass the guidewire intraluminally by Investigator evaluation across the atherosclerotic lesion, without the use of re-entry devices.
7. Calcification is at least moderate with visual evidence of calcification and at least one: 1) on parallel sides of the vessel and 2) extending ≥ 50% the length of the lesion.
8. Successful treatment without complications (≤ 30% residual stenosis) of significant stenosis or occlusion of inflow tract proximal to the target treatment zone using percutaneous angioplasty or stent, if applicable (no IVL).

Standard Exclusion Criteria:

1. Rutherford Clinical Category 0, 1, or 5 with ulcers extending proximal to the metatarsal head, Category 6, or physically unable to ambulate (e.g., bedridden).
2. Subject has active infection requiring IV antibiotics in the target leg.
3. Planned major amputation of the target leg (above the ankle joint or higher).
4. Prior endovascular or surgical procedure on the index limb within the 30 days prior to enrollment (including thrombolysis).
5. Subject has a known coagulopathy or has a bleeding diathesis, thrombocytopenia with platelet count less than 100,000/microliter, or international normalized ratio >1.5 at the time of enrollment.
6. Subject in whom antiplatelet, anticoagulant, or thrombolytic therapy is contraindicated.
7. Subject has known allergy to contrast agents or medications used to perform endovascular intervention that cannot be adequately pre-treated.
8. Myocardial infarction within 60 days prior to enrollment.
9. Stroke within 60 days prior to enrollment.
10. History of unstable coronary artery disease or other uncontrollable comorbidity resulting in hospitalization within the last 60 days prior to enrollment.
11. Subject has acute or chronic renal disease (serum creatinine of >2.5 mg/dL or eGFR <30) or is on dialysis at the time of enrollment.
12. Presence of venous insufficiency with history of venous ulceration in the target limb in the past year.
13. Subject is pregnant or nursing.
14. Subject is participating in another research study involving an investigational agent (pharmaceutical, biologic, or medical device) that has not reached the primary endpoint.
15. Subject has other medical, social or psychological problems that, in the opinion of the investigator, preclude them from receiving this treatment.

Angiographic Exclusion Criteria:

1. Any stent within the target lesion
2. Target lesion(s) within native or synthetic vessel grafts.
3. Highly tortuous arteries (bends greater than 30 degrees over the arc length of the balloon).
4. Use of: (1) CTO re-entry or (2) other non-study IVL devices on the target lesion.
5. Lesions within 10mm of the ostium of the SFA
6. Evidence of aneurysm or acute thrombus in target vessel.