Peripheral Artery Disease
Conditions
Brief summary
To assess the continued safety, effectiveness, and optimal clinical use of the Shockwave Medical Peripheral IVL System for the treatment of calcified, stenotic BTK arteries. Post-market, prospective , multi-center, single-arm study.
Interventions
Localized peripheral intravascular lithotripsy
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. Age of subject is ≥ 18. 2. Subject is able and willing to comply with all assessments in the study. 3. Subject or subject's legal representative has been informed of the nature of the study, agrees to participate, and has signed the approved consent form. 4. Critical limb ischemia (CLI) in the target limb from the distal segment (P3) of the popliteal artery to the ankle joint prior to the study procedure with Rutherford Category 4-5; or Rutherford 3 in the target limb from the distal segment (P3) of the popliteal artery to the ankle joint prior to the study procedure. 5. Estimated life expectancy \>1 year. * Angiographic Inclusion Criteria 6. Up to 2 below-the-knee target lesion(s) in native vessels in one or both limbs. 7. Target lesion reference vessel diameter (RVD) between 2.0 mm and 4.0 mm by investigator visual estimate. 8. Target lesion with ≥70% stenosis by investigator visual estimate. 9. Target lesion length is ≤200 mm by investigator visual estimate. Target lesion can be all or part of the 200 mm treated zone. 10. Distal reconstitution of at least one pedal vessel (\<50% stenosis) (desert foot excluded). 11. Evidence of at least moderate calcification at the target lesion site by angiography/IVUS OR non-dilatable lesion indicating presence of calcium. Must meet one of the following: 1. Angiography requires fluoroscopic evidence of calcification on parallel sides of the vessel and extending \> 50% the length of the lesion. 2. IVUS requires presence of ≥270 degrees of calcium over the course of at least 10mm. 3. Non-dilatable lesion requires attempted treatment with PTA during the index procedure with residual stenosis \> 50% and no serious angiographic complications.
Exclusion criteria
\- General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects Without Serious Angiographic Complications | 30 days | Subject Success defined as final residual stenosis ≤ 50% in the target lesion without serious angiographic complications as assessed by the angiographic core lab. Serious angiographic complications include (flow-limiting dissection, perforation, distal embolization, or acute vessel closure) as assessed by the angiographic core lab |
| Number of Participants With Procedure Success | 30 days | Procedure Success defined as ≤50% residual stenosis for all treated target lesions without serious angiographic complications (flow-limiting dissection, perforation, distal embolization, or acute vessel closure) as assessed by the angiographic core lab at the final timepoint. |
| Number of Participants With Major Adverse Limb Events (MALE) + Post-Operative Death (POD) | 30 days | Major Adverse Limb Events (MALE) + Post-Operative Death (POD) at 30 days defined as a composite of: * all-cause death * above-ankle amputation of the index limb * major reintervention (new bypass graft, jump/interposition graft revision, or thrombectomy/thrombolysis) of the index limb involving a BTK artery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Major Adverse Events (MAE) | 30 days | Major Adverse Events (MAE) at 30 days defined as a composite of: * 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 |
| VascuQoL Reported as Change From Baseline | 30 days, 6, 12 & 24 months | The VascuQoL-6 is a short, disease-specific questionnaire used to measure health-related quality of life (HRQoL) in patients with peripheral arterial disease (PAD), specifically those with intermittent claudication and critical limb ischemia. |
| Ankle-brachial Index (ABI) Reported as Change From Baseline | 30 days | 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 Lesions With Technical Success | 30 days | Lesion Success defined as final residual stenosis ≤50% in the target lesion without serious angiographic complications as assessed by the angiographic core lab |
| Toe-brachial Index (TBI) Reported as Change From Baseline | 30 Days | The TBI is the ratio of systolic blood pressure measured at the toe to systolic blood pressure 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 Free From Major Target Limb Amputation | 30 Days | — |
| Rutherford Category Reported as Change From Baseline | 30 days | The Rutherford classification is a system used to categorize the severity of peripheral artery disease (PAD), specifically chronic limb-threatening ischemia (CLTI), based on symptoms and tissue loss. The classification ranges are from Class 0 where no symptoms of PAD are present and the patient has no claudication or tissue loss to Class 6 where patients have extensive tissue loss, including gangrene, that extends above the transmetatarsal level (the area above the bones of the foot). A higher score on the Rutherford Classification Scale is indicative of a worse outcome. |
| Number of Patients With Primary Patency | 6 and 12 months | Primary Patency at 6 and 12 months defined as the absence of both total occlusion (100% diameter stenosis by DUS) in all of the target lesions in a flow pathway, as well as a Clinically-Driven Target Lesion Revascularization (CD-TLR) |
| Number of Participants Free From Clinically-driven Target Lesion Revascularization (CD-TLR) | 30 days | Clinically-driven target lesion revascularization (CD-TLR) defined as a composite of: * CD-TLR * Major target limb amputation |
Countries
Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Disrupt PAD BTK II Disrupt PAD BTK II: Prospective, Multi-center, Single-arm Study of the Shockwave Medical Peripheral Intravascular Lithotripsy (IVL) System for Treatment of Calcified Peripheral Arterial Disease (PAD) in Below-the-Knee (BTK) Arteries | 250 |
| Total | 250 |
Baseline characteristics
| Characteristic | Disrupt PAD BTK II |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 187 Participants |
| Age, Categorical Between 18 and 65 years | 63 Participants |
| Age, Continuous | 71.6 years STANDARD_DEVIATION 11 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 45 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race/Ethnicity, Customized Other | 4 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 14 Participants |
| Race/Ethnicity, Customized White | 181 Participants |
| Region of Enrollment Germany | 11 participants |
| Region of Enrollment United States | 239 participants |
| Sex: Female, Male Female | 68 Participants |
| Sex: Female, Male Male | 182 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 250 |
| other Total, other adverse events | 131 / 250 |
| serious Total, serious adverse events | 67 / 250 |
Outcome results
Primary
Number of Participants With Major Adverse Limb Events (MALE) + Post-Operative Death (POD)
Major Adverse Limb Events (MALE) + Post-Operative Death (POD) at 30 days defined as a composite of: * all-cause death * above-ankle amputation of the index limb * major reintervention (new bypass graft, jump/interposition graft revision, or thrombectomy/thrombolysis) of the index limb involving a BTK artery
Time frame: 30 days
Population: There were two (0.8%, 2/242) MALE events at 30 days that were adjudicated as above-ankle amputations of the index limb. Both major amputations were CEC adjudicated as unplanned amputations unrelated to the study procedure and IVL device. There were no deaths or major reinterventions within 30 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Number of Participants With Major Adverse Limb Events (MALE) + Post-Operative Death (POD) | 2 Participants |
Primary
Number of Participants With Procedure Success
Procedure Success defined as ≤50% residual stenosis for all treated target lesions without serious angiographic complications (flow-limiting dissection, perforation, distal embolization, or acute vessel closure) as assessed by the angiographic core lab at the final timepoint.
Time frame: 30 days
Population: The final procedure success at the subject level was 97.9% (232/237). There were five subjects (one subject had both angiographic complications and ≤ 50% residual stenosis) that did not have procedure success. There were three subjects with serious angiographic complications: two subjects had a grade I perforation and one subject had both an abrupt closure and grade F dissection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Number of Participants With Procedure Success | 232 Participants |
Primary
Subjects Without Serious Angiographic Complications
Subject Success defined as final residual stenosis ≤ 50% in the target lesion without serious angiographic complications as assessed by the angiographic core lab. Serious angiographic complications include (flow-limiting dissection, perforation, distal embolization, or acute vessel closure) as assessed by the angiographic core lab
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Subjects Without Serious Angiographic Complications | 234 Participants |
Secondary
Ankle-brachial Index (ABI) 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: 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Ankle-brachial Index (ABI) Reported as Change From Baseline | 0.2 ratio | Standard Deviation 0.3 |
Secondary
Number of Lesions With Technical Success
Lesion Success defined as final residual stenosis ≤50% in the target lesion without serious angiographic complications as assessed by the angiographic core lab
Time frame: 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Number of Lesions With Technical Success | Lesion Success | 285 Lesions |
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Number of Lesions With Technical Success | Freedom From Any Serious Angiographic Complications | 287 Lesions |
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Number of Lesions With Technical Success | Residual Stenosis ≤ 50% | 287 Lesions |
Secondary
Number of Participants Free From Clinically-driven Target Lesion Revascularization (CD-TLR)
Clinically-driven target lesion revascularization (CD-TLR) defined as a composite of: * CD-TLR * Major target limb amputation
Time frame: 30 days
Population: The freedom from CD-TLR endpoint at 30 days post-procedure was 99.6% (242/243).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Number of Participants Free From Clinically-driven Target Lesion Revascularization (CD-TLR) | 242 Participants |
Secondary
Number of Participants Free From Major Target Limb Amputation
Time frame: 30 Days
Population: Freedom from amputation at 30 days was assessed in 242 subjects with two subjects experiencing a major target limb amputation within 30 days of index procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Number of Participants Free From Major Target Limb Amputation | 240 Participants |
Secondary
Number of Participants With Major Adverse Events (MAE)
Major Adverse Events (MAE) at 30 days defined as a composite of: * 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, M5+, S4 Peripheral Intravascular Lithotripsy System | Number of Participants With Major Adverse Events (MAE) | 5 Participants |
Secondary
Number of Patients With Primary Patency
Primary Patency at 6 and 12 months defined as the absence of both total occlusion (100% diameter stenosis by DUS) in all of the target lesions in a flow pathway, as well as a Clinically-Driven Target Lesion Revascularization (CD-TLR)
Time frame: 6 and 12 months
Secondary
Rutherford Category Reported as Change From Baseline
The Rutherford classification is a system used to categorize the severity of peripheral artery disease (PAD), specifically chronic limb-threatening ischemia (CLTI), based on symptoms and tissue loss. The classification ranges are from Class 0 where no symptoms of PAD are present and the patient has no claudication or tissue loss to Class 6 where patients have extensive tissue loss, including gangrene, that extends above the transmetatarsal level (the area above the bones of the foot). A higher score on the Rutherford Classification Scale is indicative of a worse outcome.
Time frame: 30 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Rutherford Category Reported as Change From Baseline | 1-Mild Claudication | 21 Participants |
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Rutherford Category Reported as Change From Baseline | 2-Moderate Claudication | 14 Participants |
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Rutherford Category Reported as Change From Baseline | 3-Severe Claudication | 11 Participants |
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Rutherford Category Reported as Change From Baseline | 4-Ischemic Rest Pain | 10 Participants |
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Rutherford Category Reported as Change From Baseline | 5- Minor Tissue Loss | 102 Participants |
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Rutherford Category Reported as Change From Baseline | 6-Ulceration Or Gangrene | 1 Participants |
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Rutherford Category Reported as Change From Baseline | 0-Asymptomatic | 68 Participants |
Secondary
Toe-brachial Index (TBI) Reported as Change From Baseline
The TBI is the ratio of systolic blood pressure measured at the toe to systolic blood pressure at the brachial artery. Ideally, this ratio should be 1.0, but is often less in a subject with peripheral arterial disease.
Time frame: 30 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Shockwave Medical M5, M5+, S4 Peripheral Intravascular Lithotripsy System | Toe-brachial Index (TBI) Reported as Change From Baseline | 0.2 ratio | Standard Deviation 0.2 |
Secondary
VascuQoL Reported as Change From Baseline
The VascuQoL-6 is a short, disease-specific questionnaire used to measure health-related quality of life (HRQoL) in patients with peripheral arterial disease (PAD), specifically those with intermittent claudication and critical limb ischemia.
Time frame: 30 days, 6, 12 & 24 months