Peripheral Arterial Disease, Vascular Disease, Peripheral
Conditions
Brief summary
Prospective, multi-center, single-arm study of the M5+ Peripheral IVL system to treat calcified peripheral arteries.
Detailed description
The objective of this study is to assess the safety and performance of the Shockwave M5+ Peripheral IVL System to treat calcified peripheral arteries in pre-market countries, and to assess continued safety and effectiveness in the US. A minimum of 40 lesions in up to 40 subjects at up to 10 sites in Australia, New Zealand and the US will be enrolled with the aim of treating at least 20 target lesions with the 8.0 mm IVL catheter. A maximum of three target lesions may be treated per subject. Subjects with moderate and severely calcified iliac and femoropopliteal artery disease presenting with Rutherford Category 2 to 5. Approximately 6 months of enrollment at up to 10 sites in Australia, New Zealand and the US. Study subjects will be followed through discharge, 30 days, 6 and 12 months. Duplex Ultrasound (DUS) assessments will be completed at 12 months. Total anticipated study duration is 18 months. The primary safety endpoint is Major Adverse Events (MAE) at 30 days defined as: need for emergency surgical revascularization of target limb; unplanned target limb major amputation (above the ankle); symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic means to improve flow and extend hospitalization ; or perforations that require an intervention, including bail-out stenting. The primary performance endpoint is technical success defined as final residual stenosis ≤30% without flow-limiting dissection (≥ Grade D) of the lesion by angiographic core lab.
Interventions
DEVICEShockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL)
The Shockwave Medical M5+ Peripheral IVL System is indicated for lithotripsy-enhanced, low-pressure balloon dilatation of lesions, including calcified lesions, in the peripheral vasculature, including the iliac, femoral, ilio-femoral, popliteal, infra-popliteal, and renal arteries. This device is not intended for use in coronary, carotid, or cerebrovascular arteries.
Sponsors
Shockwave Medical, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria 1. Subject is able and willing to comply with all assessments in the study. 2. Subject or subject's legal representative have been informed of the nature of the study, agrees to participate and has signed the approved consent form. 3. Age of subject is \> 18. 4. Rutherford Clinical Category 2, 3, 4 or 5 of the target limb(s). 5. Estimated life expectancy \>1 year. 6. Subject is intended to undergo treatment with Shockwave M5+ Peripheral IVL System for de novo lesions of the ilio-femoropopliteal arteries. Angiographic Inclusion Criteria 7. Single or multiple de novo target lesion(s) located from the common iliac to the femoropopliteal artery, in one or both limbs. 8. Target lesion reference vessel diameter is between 3.5mm and 8.0mm by visual estimate. 9. Target lesion is ≥70% stenosis by investigator via visual estimate. 10. Target lesion length is ≤200mm for lesions 70-99% stenosed. Target lesion can be all or part of the 200mm treated zone. 11. Chronic total occlusion, lesion length is ≤100mm of the total ≤200 mm target lesion. 12. Subject has at least one patent tibial vessel on the target leg with runoff to the foot, defined as no stenosis \>50%. 13. Calcification is at least moderate defined as presence of fluoroscopic evidence of calcification: 1) on parallel sides of the vessel and 2) extending \> 50% the length of the lesion if lesion is ≥50mm in length; or extending for minimum of 20mm if lesion is \<50mm in length. General
Exclusion criteria
1. Rutherford Clinical Category 0, 1, and 6. 2. Subject has active infection requiring antibiotic therapy. 3. History of endovascular or surgical procedure on the target limb within the last 30 days or planned within 30 days of the index procedure. Note: Concomitant IVL treatment to facilitate large bore access at the time of procedure is allowed. 4. Subject in whom antiplatelet or anticoagulant therapy is contraindicated. 5. Subject has known allergy to contrast agents or medications used to perform endovascular intervention that cannot be adequately pre-treated. 6. Subject has known allergy to urethane, nylon, or silicone. 7. Myocardial infarction within 60 days prior to enrollment. 8. History of stroke within 60 days prior to enrollment. 9. Subject has acute or chronic renal disease defined as serum creatinine of \>2.5 mg/dL or \>220 umol/L, unless on dialysis. 10. Subject is pregnant or nursing. 11. Subject is participating in another research study involving an investigational agent (pharmaceutical, biologic, or medical device) that has not reached the primary endpoint. 12. Subject has other medical, social or psychological problems that, in the opinion of the investigator, preclude them from receiving this treatment, and the procedures and evaluations pre- and post-treatment. 13. The planned use of specialty balloons, re-entry or atherectomy devices in the target lesion(s). Angiographic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Major Adverse Events (MAE) | 30 days | Defined as: Need for emergency surgical revascularization of target limb * Unplanned target limb major amputation (above the ankle) * Symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic means to improve flow and extend hospitalization * Perforations that require an intervention, including bail-out stenting |
| Number of Lesions With Technical Success | Peri-procedural, approximately 2 hours | Defined as final residual stenosis ≤30% without flow-limiting dissection (≥ Grade D) of the lesion by angiographic core lab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically-driven Target Lesion Revascularization (TLR) | 30 days | A target lesion revascularization performed due to target lesion diameter stenosis ≥50% and either evidence of clinical or functional ischemia (e.g., recurrent/progressive life-limiting intermittent claudication, claudication unresponsive to medical therapy, CLI) or recurrence of the clinical syndrome for which the initial procedure was performed. Clinically driven target lesion revascularization occurs in the absence of protocol directed surveillance ultrasound or angiography. |
| Rutherford Category Reported as Change From Baseline | 30 days | Number of Participants with Improvement in Rutherford Score from as reported at 30 days post-procedure |
| Number of Lesions With IVL Technical Success | Peri-procedural, approximately 2 hours | Defined as residual stenosis ≤30% without flow-limiting dissection (≥ Grade D) of the lesion post-IVL by angiographic core lab |
| Number of Participants With Primary Patency | 12 months | Defined as freedom from clinically-driven target lesion revascularization (TLR) and freedom from restenosis determined by duplex ultrasound or angiogram ≥50% stenosis |
| Ankle-brachial Index (ABI) Reported as Change From Baseline | 12 months | ABI at 12 months reported as change from baseline. The ABI is the ratio of systolic blood pressure measured at the ankle to systolic blood pressure measured at the brachial artery. Ideally, this ratio should be 1.0, but is often less in a subject with peripheral arterial disease. |
| Number of Participants With Major Adverse Events (MAE) | 6 months | * Need for emergency surgical revascularization of target limb * Unplanned target limb major amputation (above the ankle) * Symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic means to improve flow and extend hospitalization * Perforations that require an intervention, including bail-out stenting |
| Number of Participants With Procedural Success | Peri-procedural, approximately 2 hours | Defined as final residual stenosis ≤30% without any flow-limiting dissection (≥ Grade D) in all target lesions by angiographic core lab |
Countries
Australia, New Zealand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL): The Shockwave Medical M5+ Peripheral IVL System is indicated for lithotripsy-enhanced, low-pressure balloon dilatation of lesions, including calcified lesions, in the peripheral vasculature, including the iliac, femoral, ilio-femoral, popliteal, infra-popliteal, and renal arteries. This device is not intended for use in coronary, carotid, or cerebrovascular arteries. | 37 |
| Total | 37 |
Baseline characteristics
| Characteristic | Single Arm |
|---|---|
| Age, Continuous | 69.7 years STANDARD_DEVIATION 10.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment Australia | 10 participants |
| Region of Enrollment New Zealand | 17 participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 37 |
| other Total, other adverse events | 36 / 37 |
| serious Total, serious adverse events | 20 / 37 |
Outcome results
Primary
Number of Lesions With Technical Success
Defined as final residual stenosis ≤30% without flow-limiting dissection (≥ Grade D) of the lesion by angiographic core lab.
Time frame: Peri-procedural, approximately 2 hours
Population: Technical success is on a per lesion basis, not per subject.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Number of Lesions With Technical Success | 43 Lesions |
Primary
Number of Participants With Major Adverse Events (MAE)
Defined as: Need for emergency surgical revascularization of target limb * Unplanned target limb major amputation (above the ankle) * Symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic means to improve flow and extend hospitalization * Perforations that require an intervention, including bail-out stenting
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Number of Participants With Major Adverse Events (MAE) | 0 Participants |
Secondary
Ankle-brachial Index (ABI) Reported as Change From Baseline
ABI at 12 months reported as change from baseline. The ABI is the ratio of systolic blood pressure measured at the ankle to systolic blood pressure measured at the brachial artery. Ideally, this ratio should be 1.0, but is often less in a subject with peripheral arterial disease.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Ankle-brachial Index (ABI) Reported as Change From Baseline | 0.3 ratio | Standard Deviation 0.5 |
Secondary
Number of Lesions With IVL Technical Success
Defined as residual stenosis ≤30% without flow-limiting dissection (≥ Grade D) of the lesion post-IVL by angiographic core lab
Time frame: Peri-procedural, approximately 2 hours
Population: IVL Technical Success was calculated on a per lesion basis, not per subject.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Number of Lesions With IVL Technical Success | 28 Lesions |
Secondary
Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)
A target lesion revascularization performed due to target lesion diameter stenosis ≥50% and either evidence of clinical or functional ischemia (e.g., recurrent/progressive life-limiting intermittent claudication, claudication unresponsive to medical therapy, CLI) or recurrence of the clinical syndrome for which the initial procedure was performed. Clinically driven target lesion revascularization occurs in the absence of protocol directed surveillance ultrasound or angiography.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Number of Participants With Clinically-driven Target Lesion Revascularization (TLR) | 0 Participants |
Secondary
Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)
A target lesion revascularization performed due to target lesion diameter stenosis ≥50% and either evidence of clinical or functional ischemia (e.g., recurrent/progressive life-limiting intermittent claudication, claudication unresponsive to medical therapy, CLI) or recurrence of the clinical syndrome for which the initial procedure was performed. Clinically driven target lesion revascularization occurs in the absence of protocol directed surveillance ultrasound or angiography.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Number of Participants With Clinically-driven Target Lesion Revascularization (TLR) | 3 Participants |
Secondary
Number of Participants With Clinically-driven Target Lesion Revascularization (TLR)
A target lesion revascularization performed due to target lesion diameter stenosis ≥50% and either evidence of clinical or functional ischemia (e.g., recurrent/progressive life-limiting intermittent claudication, claudication unresponsive to medical therapy, CLI) or recurrence of the clinical syndrome for which the initial procedure was performed. Clinically driven target lesion revascularization occurs in the absence of protocol directed surveillance ultrasound or angiography.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Number of Participants With Clinically-driven Target Lesion Revascularization (TLR) | 0 Participants |
Secondary
Number of Participants With Major Adverse Events (MAE)
* Need for emergency surgical revascularization of target limb * Unplanned target limb major amputation (above the ankle) * Symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic means to improve flow and extend hospitalization * Perforations that require an intervention, including bail-out stenting
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Number of Participants With Major Adverse Events (MAE) | 1 Participants |
Secondary
Number of Participants With Major Adverse Events (MAE)
* Need for emergency surgical revascularization of target limb * Unplanned target limb major amputation (above the ankle) * Symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic means to improve flow and extend hospitalization * Perforations that require an intervention, including bail-out stenting
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Number of Participants With Major Adverse Events (MAE) | 1 Participants |
Secondary
Number of Participants With Primary Patency
Defined as freedom from clinically-driven target lesion revascularization (TLR) and freedom from restenosis determined by duplex ultrasound or angiogram ≥50% stenosis
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Number of Participants With Primary Patency | 21 Participants |
Secondary
Number of Participants With Procedural Success
Defined as final residual stenosis ≤30% without any flow-limiting dissection (≥ Grade D) in all target lesions by angiographic core lab
Time frame: Peri-procedural, approximately 2 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Number of Participants With Procedural Success | 30 Participants |
Secondary
Rutherford Category Reported as Change From Baseline
Number of Participants with Improvement in Rutherford Score from as reported at 12 Months post-procedure.
Time frame: 12 months
Population: Improved from baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Rutherford Category Reported as Change From Baseline | 24 Participants |
Secondary
Rutherford Category Reported as Change From Baseline
Number of Participants with Improvement in Rutherford Score from as reported at 6 months post-procedure
Time frame: 6 months
Population: Improved from baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Rutherford Category Reported as Change From Baseline | 26 Participants |
Secondary
Rutherford Category Reported as Change From Baseline
Number of Participants with Improvement in Rutherford Score from as reported at 30 days post-procedure
Time frame: 30 days
Population: Improved from baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5+ Peripheral Intravascular Lithotripsy (IVL) | Rutherford Category Reported as Change From Baseline | 27 Participants |