Study of the Shockwave Medical SkyRunner Carotid Intravascular Lithotripsy (IVL) System for the Treatment of Calcified Carotid Arteries Prior to Trans-Femoral Stenting (SKYWARD Trans-Femoral IDE [Investigational Device Exemption] Study) (SKYWARD TF)

Prospective, Multi-center, Single-arm Study of the Shockwave Medical SkyRunner Carotid Intravascular Lithotripsy (IVL) System for the Treatment of Calcified Carotid Arteries Prior to Trans-Femoral Stenting (SKYWARD Trans-Femoral IDE Study)

Prospective, Multi-center, Single-arm Study of the Shockwave Medical SkyRunner Carotid Intravascular Lithotripsy (IVL) System for the Treatment of Calcified Carotid Arteries Prior to Trans-Femoral stenting (SKYWARD Trans-Femoral IDE Study)

Study Overview

• Status: Not yet recruiting
• Conditions: Carotid Artery Diseases; Carotid Artery Calcification
• Intervention / Treatment: Device: Carotid Intravascular Lithotripsy

Detailed Description

To assess the safety and effectiveness of the Shockwave Medical SkyRunner Carotid IVL System for the treatment of calcified carotid arteries prior to stenting with commercially available trans-femoral stent systems in patients at high risk for complications from carotid endarterectomy (CEA). Up to 160 subjects at up to 25 sites in the United States (US) in the primary analysis cohort. Additionally, one roll-in subject must be enrolled per site for up to 25 roll-in subjects. These roll-in subjects will not count toward the up to 160 subject target enrollment for the primary analysis cohort. The estimated study duration is approximately 76 months. Study subjects will be followed through discharge, 30 days, 6, 12, 24, 36, 48, and 60 months.

• Study Type: Interventional
• Enrollment (Estimated): 185
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Danilo Romero Romero; Phone Number: 510-279-4262; Email: DRomer28@its.jnj.com
• Study Contact Backup: Name: Birgit Greschner; Phone Number: 510-279-4262; Email: BGreschn@its.jnj.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

General Inclusion Criteria:

1. Age ≥ 18 years.
2. Patient is able and willing to comply with all assessments in the study.
3. Patient has been informed of the nature of the study, agrees to participate and has signed the approved informed consent form.
4. Patient approved for inclusion by a Patient Screening Committee.

5. Patient must have a life expectancy > 1 year at the time of the index procedure, in the opinion of the investigator at the time of enrollment, with no planned major cardiac intervention or surgery within 30 days following the index procedure.

   Angiographic Inclusion Criteria:

6. Patient has a discrete lesion located in the internal carotid artery (ICA) with or without involvement of the carotid bifurcation.
7. Target lesion must meet all requirements for commercially available trans-femoral stent systems (refer to IFU for requirements) and investigator intends to treat the target lesion with a single stent.

8. Patient must meet one of the following criteria regarding neurological symptom status and degree of stenosis by duplex ultrasound in combination with CT or MR angiography:

   1. Symptomatic: ≥ 50% stenosis of the internal carotid artery and the patient has a history of stroke, TIA and/or amaurosis fugax within 180 days of the procedure ipsilateral to the carotid artery to be treated.

      OR

   2. Asymptomatic: ≥ 70% stenosis of the internal carotid artery without any neurological symptoms.
9. Patient has evidence of circumferential calcification of the stenotic lesion defined as ≥ 3 mm thickness of calcification as determined by Computed Tomography Angiography (CTA). MR angiography may be used in place of CTA for patients with a relative or absolute contraindication to CTA.
10. Patient is high risk for CEA defined as meeting at least one anatomic or clinical high-risk condition listed below:

Anatomic High Risk Inclusion Criteria:

• Target lesion at or above C2 (level of jaw) or below the clavicle
• Inability to extend the head due to cervical arthritis or other cervical disorders
• History of radiation treatment to the neck or radical neck dissection
• Prior head and neck surgery in the region of the carotid artery
• Spinal immobility of the neck
• Tracheostomy or tracheostoma
• Hostile neck or surgically inaccessible lesion
• Laryngeal palsy or laryngectomy
• Severe tandem lesions (total length must be ≤ 30 mm and must be covered with one stent)
• Occlusion of the contralateral CCA or ICA
• Severe bilateral ICA stenosis

Clinical High-Risk Inclusion Criteria

• Patient is ≥ 70 years of age.
• Patient has congestive heart failure (CHF) - New York Heart Association (NYHA) Functional Class III or IV.
• Patient has severe pulmonary disease (COPD) with either FEV < 50% predicted or chronic oxygen therapy or resting PO2 of < 60 mmHg (room air).
• Patient has a history of angina Canadian Cardiovascular Society (CCS) class 3 or 4 or unstable angina.
• Patient has known severe left ventricular dysfunction LVEF < 30%.
• Patient had a myocardial infarction > 72 hours and < 6 weeks prior to procedure.
• Coronary artery disease with two or more vessels with ≥ 70% stenosis.
• Planned coronary artery bypass grafting (CABG) or valve replacement surgery between 31 and 60 days after index procedure.
• Patient has permanent contralateral cranial nerve injury/paralysis.
• Patient has chronic renal insufficiency (serum creatinine ≥ 2.5 mg/dL). Note that patients on dialysis are excluded from study consideration per exclusionary criterion #13.
• Planned abdominal aortic aneurysm repair or peripheral vascular surgery between 31 to 60 days after index procedure.

General Exclusion Criteria:

1. Patient has alternative source of cerebral embolus, including but not limited to:

   1. a history of chronic atrial flutter or atrial fibrillation, or paroxysmal atrial flutter or atrial fibrillation requiring chronic anticoagulation
   2. knowledge of cardiac sources of emboli (e.g. left ventricular aneurysm, intracardiac filling defect, cardiomyopathy, aortic or mitral prosthetic heart valve, hemodynamically significant aortic stenosis, endocarditis, mitral stenosis, or left atrial myxoma)
   3. recently (< 60 days) replaced/repaired heart valve (either surgically or percutaneously).
2. Patient has a history of spontaneous intracranial hemorrhage within the past 12 months, a hemorrhagic transformation of an ischemic stroke within the past 60 days or has had a recent stroke (< 7 days) of sufficient size (on CT or MRI) to place the patient at risk of hemorrhagic conversion during the procedure.
3. Patient with a history of major stroke with substantial neurological deficit (NIHSS ≥ 5 or mRS ≥ 3) within 1 month of index procedure.
4. Patient has had a TIA, or amaurosis fugax within 48 hours prior to the procedure.
5. Patient has neurologic illnesses within the past 2 years characterized by fleeting or fixed neurologic or cognitive deficit which cannot be distinguished from TIA or stroke.
6. Patient has an intracranial tumor.
7. Patient has an unresolved/uncorrected bleeding disorder.
8. Patient had a myocardial infarction (MI) within last 72 hours prior to index procedure.
9. Patient has history of intolerance or allergic reaction to contrast material that cannot be adequately premedicated or to any of the required study medications (i.e., antiplatelet agents, statins) or device materials (refer to IFUs).
10. Female patients who are pregnant, nursing, or may become pregnant.
11. Patient is participating in another research study involving an investigational agent (pharmaceutical, biologic, or medical device) that has not reached its primary endpoint.
12. Patient has other medical, social, or psychological problems that, in the opinion of the investigator, would present difficulty in complying with protocol requirements.

13. Patient is on renal replacement therapy (i.e., dialysis).

    Angiographic Exclusion Criteria:

14. Presence of a previously placed intravascular stent in the target vessel or ipsilateral CCA.
15. A significant CCA inflow or distal/intracranial lesion.
16. Occlusion (TICI 0) or "string sign" > 1 cm of the ipsilateral common or internal carotid artery.
17. An intraluminal filling defect consistent with thrombus.
18. Presence of extensive or diffuse atherosclerotic disease involving the aortic arch or proximal common carotid artery that would preclude the safe introduction of the study device.
19. Cerebral aneurysm, symptomatic or > 5 mm or AVM (arteriovenous malformation) of the cerebral vasculature.
20. Massive exophytic (mushroom-like) or irregular endoluminal calcification seen on CTA or fluoroscopy.
21. Failure to successfully cross the guidewire across the target lesion; successful crossing defined as tip of the guidewire distal to the target lesion.
22. Type III or Bovine aortic arch anatomy.
23. Angulation or tortuosity (≥ 90 degree) of the innominate and common carotid artery (CCA) that precludes safe, expeditious sheath placement or that will transmit a severe loop to the internal carotid after sheath placement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Calcified Carotid Artery; Up to 160 subjects for the primary analysis cohort, with 25 additional roll-in subjects, with calcified carotid arteries to be treated with intravascular lithotripsy (IVL) prior to stenting with commercially available trans-femoral stent systems in patients at high risk for complications from carotid endarterectomy (CEA) will be enrolled in the study.

Device: Carotid Intravascular Lithotripsy; The Shockwave Medical Intravascular Lithotripsy (IVL) System with the Shockwave SkyRunner Carotid IVL Catheter is intended for lithotripsy- enhanced balloon dilatation of calcified lesions in the carotid arteries prior to stenting. Not for use treating massive exophytic (mushroom-like) or irregular endoluminal carotid calcification, or in the coronary or cerebral arteries.; Other Names: Intravascular Lithotripsy (IVL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Endpoint: Composite endpoint with death, stroke, or myocardial infarction (MI) [Safety]	A composite endpoint with death, stroke (disabling or non-disabling based on NeuroARC definitions) or myocardial infarction (MI) (using the SCAI definition for peri-procedural MI and the 4th Universal Definition for spontaneous MI beyond 48 hours) at 30 days post procedure.	30 days post procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with residual diameter stenosis ≤ 50%	Proportion of subjects with stent delivery with a residual diameter stenosis ≤ 50% (core lab assessed) on final angiography.	Day 0
Proportion of subjects with a residual stenosis of ≤ 30%	Proportion of subjects with stent delivery with a residual stenosis of ≤ 30% (core lab assessed) on final angiography.	Day 0
Cranial Nerve Assessment for Cranial nerve injury	Cranial Nerve Assessment for cranial nerve injury at discharge, 30 days, 6, 12 and 24 months.	Day 0, 30 days, 6, 12, and 24 months post procedure
Incidence of all cause death	Incidence of all cause death, at 30 days, 6, 12, 24, 36, 48 and 60 months.	30 days, 6, 12, 24, 36, 48 and 60 months post procedure
Incidence of any stroke	Incidence of any stroke through 30 days, 6, 12, 24, 36, 48 and 60 months of follow-up, categorized as: Disabling or Non-disabling; Ipsilateral or Contralateral; Hemorrhagic, Ischemic, or Unknown	30 days, 6, 12, 24, 36, 48 and 60 months post procedure
Proportion of subjects with Device Success without serious angiographic complications	Proportion of subjects with Device Success, defined as the ability of the IVL catheter to fully cross the target lesion and delivery of lithotripsy without core lab adjudicated serious angiographic complications, defined as severe dissection (Grade D to F), perforation, abrupt closure, or distal embolization on final angiography, as assessed by the core lab.	Day 0
Incidence of Myocardial Infarction (MI)	Incidence of Myocardial Infarction (MI) (using the SCAI definition for peri- procedural MI; using the 4th Universal Definition for spontaneous MI beyond 48 hours) at discharge, 30 days, 6, 12, 24, 36, 48 and 60 months.	Day 0, 30 days, 6, 12, 24, 36, 48 and 60 months post procedure
Incidence of Transient Ischemic Attack (TIA)	Incidence of Transient Ischemic Attack (TIA) at discharge, 30 days, 6, 12, 24, 36, 48 and 60 months	Day 0, 30 days, 6, 12, 24, 36, 48 and 60 months post procedure
Number of patients with change in NIH Stroke Scale	Change in NIH Stroke Scale (NIHSS) at discharge, 30 days, 6, 12 and 24 months.	Day 0, 30 days, 6, 12, and 24 months post procedure
Neurological function assessed by Modified Rankin Scale (mRS)	Neurological assessment by Modified Rankin Scale at discharge, 30 days, 6, 12 and 24 months. Grade 0 - No symptoms Grade 1 - No significant disability despite symptoms Grade 2 - Slight Disability Grade 3 - Moderate Disability Grade 4 - Moderately Severe Disability Grade 5 - Severe Disability Grade 6 - Deceased	Day 0, 30 days, 6, 12, and 24 months post procedure
Incidence of Clinically-Driven target lesion revascularization (CD-TLR)	Incidence of Clinically-driven target lesion revascularization (CD-TLR), adjudicated by the CEC, at discharge, 30 days, 6, 12, 24, 36, 48 and 60 months.	Day 0, 30 days, 6, 12, 24, 36, 48 and 60 months post procedure
Incidence of in-stent restenosis as assessed by DUS core lab	Incidence of in-stent restenosis (defined as > 70% restenosis per Duplex Ultrasound (DUS), assessed by DUS core lab, at 6, 12, and 24 months.	6, 12, and 24 months post procedure

Collaborators and Investigators

• Sponsor: Shockwave Medical, Inc.
• Collaborators: Massachusetts General Hospital; Medpace, Inc.; Yale Cardiovascular Research Group; Cardiovascular Research Foundation, New York

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: IVL; Calcification; Carotid Calcification
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolic Diseases; Calcium Metabolism Disorders; Nutritional and Metabolic Diseases; Carotid Artery Diseases; Calcinosis
• Other Study ID Numbers: CP 75490

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes