Trial Outcomes & Findings for Study of SilverHawk®/TurboHawk® in Lower Extremity Vessels (DEFINITIVE™ LE) (NCT NCT00883246)

Last Updated: 2019-06-04

Results Overview

The primary endpoint analysis for claudication subjects was primary patency rate at one year, defined by duplex ultrasound measurement of peak systolic velocity ratio ≤ 3.5 at the target lesion(s) with no clinically-driven reintervention within the treated segment in subjects who had claudication (RCC of 1 - 3) at time of enrollment.

Recruitment status

COMPLETED

Study phase

Target enrollment

800 participants

Primary outcome timeframe

One year

Results posted on

2019-06-04

Participant Flow

Subjects with all severities of peripheral arterial disease were recruited for this single-arm study. Outcome measures may apply to all subjects or be specific to level of disease severity (ie subjects w/claudication RCC1-3, subjects w/critical limb ischemia RCC4 (no wounds) or RCC5-6 (with wounds)). These are specified in the Arm/Group titles.

800 subjects were enrolled. One subject was excluded from all data analyses due to an invalid informed consent and was not considered started.

Participant milestones

Participant milestones
Measure	Atherectomy All patients enrolled in this single-arm study were treated with directional atherectomy. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Overall Study STARTED	799
Overall Study COMPLETED	626
Overall Study NOT COMPLETED	173

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of SilverHawk®/TurboHawk® in Lower Extremity Vessels (DEFINITIVE™ LE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atherectomy n=799 Participants All patients enrolled in this single-arm study were treated with directional atherectomy. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	259 Participants n=93 Participants
Age, Categorical >=65 years	540 Participants n=93 Participants
Age, Continuous	70.1 years STANDARD_DEVIATION 10.7 • n=93 Participants
Sex: Female, Male Female	363 Participants n=93 Participants
Sex: Female, Male Male	436 Participants n=93 Participants
Region of Enrollment Europe	107 participants n=93 Participants
Region of Enrollment United States	692 participants n=93 Participants
Diabetes Diabetes	418 participants n=93 Participants
Diabetes No Diabetes	381 participants n=93 Participants

PRIMARY outcome

Timeframe: One year

Population: Kaplan-Meier estimate of the freedom from loss of primary patency in lesions (N=743 lesions)

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=743 Number of Lesions Analyzed Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Primary Patency Rate (in Patients Treated for Claudication RCC 1-3)	81.6 percentage of lesions by Kaplan Meier	—

PRIMARY outcome

Timeframe: One Year

The primary endpoint for CLI was amputation-free survival at one year, defined as freedom from a major, unplanned amputation of the target limb through the 1-year visit in subjects who have CLI (RCC 4 - 6) at time of enrollment.

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=201 Participants Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Amputation-Free Survival at 1 Year (in Patients Treated for Critical Limb Ischemia RCC 4-6)	95.1 percentage of subjects by Kaplan-Meier	—

SECONDARY outcome

Timeframe: Immediately following use of the SilverHawk device

Population: Lesions with core angiographic laboratory measurements of residual stenosis

Device success was defined as ≤ 30% residual stenosis following use of the SilverHawk device, as measured by angiography, without adjunctive endovascular interventions or periprocedural complications.

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=999 Number of Lesions Analyzed Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Device Success (in All Patients Enrolled)	70.5 percentage of Lesions	—

SECONDARY outcome

Timeframe: Immediately following use of the SilverHawk and adjunctive devices

Population: All lesions with angiographic core lab assessment of residual stenosis at the end of the procedure were included

Procedure success was defined as ≤ 30% residual stenosis following use of SilverHawk device and adjunctive endovascular interventions (if required) as measured by angiography without periprocedural complications.

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=1015 Number of Lesions Analyzed Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Procedural Success (in All Patients Enrolled)	84.0 percentage of lesions	—

SECONDARY outcome

Timeframe: 30 Days

Major Adverse Event Rate (MAE) at 30 Days was defined as clinically-driven target vessel revascularization (TVR), major unplanned amputation of treated limb, or all-cause mortality within 30 days post procedure, as classified by the Clinical Events Committee (CEC).

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=799 Participants Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Major Adverse Event Rate (in All Patients Enrolled)	1.6 percentage of patients	—

SECONDARY outcome

Timeframe: One Year

Major Adverse Event Rate at One Year was defined as clinically-driven target vessel revascularization, major unplanned amputation of the treated limb, or all-cause mortality within one year, as classified by the Clinical Events Committee (CEC).

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=799 Participants Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Major Adverse Event Rate (in All Patients Enrolled)	20.9 percentage of patients	—

SECONDARY outcome

Timeframe: Baseline and 1 Year

Population: All subjects treated for claudication RCC 1-3 with completed WIQ forms

WIQ includes a measurement for walking distance, walking speed, and climbing stairs collected at baseline and one year, presented for subjects who have claudication. The Walking Improvement Questionnaire (WIQ) is a validated method to assess objective improvement in functional walking ability of subjects with intermittent claudication. Difficulty walking a distance was self-assessed at baseline by the patient (prior to treatment) and at the one year follow up visit. Speed and stair climbing ability were assessed by the treating physician. Scale ranges from 0 (minimum) to 100 (maximum), with larger numbers representing better outcomes. An increase in WIQ scores at 1 year represents an improvement over baseline.

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=590 Participants Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) n=464 Participants All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Improvement in Walking Impairment Questionnaire Score (in Patients Treated for Claudication RCC 1-3) Walking Distance Score	19.9 units on a scale Standard Deviation 24.2	49.5 units on a scale Standard Deviation 38.0
Improvement in Walking Impairment Questionnaire Score (in Patients Treated for Claudication RCC 1-3) Walking Speed Score	20.3 units on a scale Standard Deviation 20.7	39.4 units on a scale Standard Deviation 28.8
Improvement in Walking Impairment Questionnaire Score (in Patients Treated for Claudication RCC 1-3) Stair Climbins Score	32.0 units on a scale Standard Deviation 31.0	53.9 units on a scale Standard Deviation 37.6

SECONDARY outcome

Timeframe: 1 Year

Population: All patients with RCC data at baseline and 1 year

Change in RCC at One Year was assessed and percentage of subjects with an improvement in clinical status indicated by a decrease of one or more in RCC at one year compared to baseline, that is attributable to the treated limb (in cases of bilateral disease), was calculated.

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=616 Participants Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Improvement in Rutherford Clinical Category (in All Patients Enrolled)	82.3 percentage of patients	—

SECONDARY outcome

Timeframe: 1 Year

Population: All patients with compressible arteries and a baseline ABI \< 0.9.

Change in Ankle-Brachial Index at One Year was calculated and percentage of subjects with an increase (improvement) in the ankle-brachial index (ABI) at one year compared to baseline in subjects with compressible arteries and baseline ABI \< 0.9 was calculated.

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=429 Participants Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Ankle-Brachial Index (in All Patients Enrolled)	76 percentage of patients improved	—

SECONDARY outcome

Timeframe: One Year

Population: All claudicants.

Secondary patency was defined as measured by duplex ultrasound peak systolic velocity ratio ≤ 3.5 maintained by repeat percutaneous intervention in subjects who have claudication; estimated as freedom from loss of patency by the Kaplan-Meier method at one year.

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=743 Number of Lesions Analyzed Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Secondary Patency (in Patients Treated for Claudication RCC 1-3)	93.5 percentage of lesions	—

SECONDARY outcome

Timeframe: One Year

Population: All patients with CLI.

The primary patency for CLI was defined by duplex ultrasound measurement of peak systolic velocity ratio ≤ 3.5 at the target lesion(s) with no clinically-driven reintervention within the treated segment in subjects who have CLI at time of enrollment

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=279 Number of Lesions Analyzed Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Primary Patency (in Patients Treated for Critical Limb Ischemia RCC 4-6)	74.1 percentage of lesions	—

SECONDARY outcome

Timeframe: One Year

Population: All claudicants.

Amputation-Free Survival in Claudicants at One Year was defined as freedom from a major, unplanned amputation of the target limb through the one year visit in subjects who have claudication at time of enrollment.

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=598 Participants Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Amputation-Free Survival (in Patients Treated for Claudication RCC 1-3)	99.6 percentage of patients by Kaplan-Meier	—

SECONDARY outcome

Timeframe: 3 months

Population: Patients with wounds at baseline who had wound assessment scores at baseline and at 3 months.

Wound healing at three months was defined as a decrease of at least one Wagner Classification grade of the wound at three months compared to baseline in subjects who have Rutherford Clinical Category score of 5 or 6 at the time of enrollment.

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=103 Participants Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Improvement in Wound Healing (in Patients Treated for Critical Limb Ischemia and With Wounds RCC 5-6)	61.2 percentage of patients	—

SECONDARY outcome

Timeframe: 1 year

Population: Lesions in patients with claudication at baseline

Defined by the duplex ultrasound measurement of peak systolic velocity ration ≤ 2.4 at the target lesion (s) with no clinically-driven re- intervention with the treated segment in subjects who have claudication at time of enrollment.

Outcome measures

Outcome measures
Measure	Claudicant Subgroup n=743 Number of Lesions Analyzed Subjects who had claudication (RCC of 1 - 3) at time of enrollment.	Claudicant Subgroup (One Year) All claudicant subjects (RCC 1-3) enrolled in this single-arm study were treated with directional atherectomy and walking distance measured at the one year follow-up visit. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Alternative Patency Rate (Peak Systolic Velocity ≤ 2.4) at 1 Year (in Patients Treated for Claudication RCC 1-3)	77.5 percentage of lesions by Kaplan-Meier	—

Adverse Events

All Patients

Serious events: 410 serious events

Other events: 41 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	All Patients n=799 participants at risk All patients enrolled in this single-arm study were treated with directional atherectomy. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Vascular disorders Abrupt closure	0.38% 3/799 • Number of events 4 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Access site complication	2.0% 16/799 • Number of events 16 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Arterial dissection (Grade D or greater)	0.63% 5/799 • Number of events 5 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Arterial Spasm	0.38% 3/799 • Number of events 3 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Arterial thrombosis	1.1% 9/799 • Number of events 10 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Arterio-venous fistula	0.13% 1/799 • Number of events 1 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Bleeding complications	1.4% 11/799 • Number of events 12 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Cellulitis	0.63% 5/799 • Number of events 5 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Hypertension	0.13% 1/799 • Number of events 1 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Hypotention	0.50% 4/799 • Number of events 4 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Infections and infestations Infection (not at access site)	6.0% 48/799 • Number of events 70 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Myocardial Infarction	2.1% 17/799 • Number of events 18 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Other	34.9% 279/799 • Number of events 458 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Pseudoaneurysm not at the access site	0.13% 1/799 • Number of events 1 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Renal and urinary disorders renal failure	1.0% 8/799 • Number of events 8 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Renal and urinary disorders Renal Insufficiency	0.13% 1/799 • Number of events 1 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Restenosis	21.3% 170/799 • Number of events 218 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Infections and infestations Sepsis	0.88% 7/799 • Number of events 9 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders stroke	0.88% 7/799 • Number of events 7 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Sub-acute Closure	0.13% 1/799 • Number of events 1 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Vascular disorders Tansient ischemic attack	0.75% 6/799 • Number of events 6 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Infections and infestations Wound abscess	0.13% 1/799 • Number of events 1 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).
Surgical and medical procedures wound debridement	0.25% 2/799 • Number of events 2 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).

Other adverse events

Other adverse events
Measure	All Patients n=799 participants at risk All patients enrolled in this single-arm study were treated with directional atherectomy. SilverHawk Peripheral Plaque Excision System: Removal of atherosclerotic plaque from artery walls.
Vascular disorders Arterial perforation	5.1% 41/799 • Number of events 42 • Adverse events were collected throughout the 12 month follow-up of the study. Adverse events were reviewed and classified by a third party clinical events committee. AEs were classified as device-related and/or procedure-related, as well as Serious Adverse Events (SAEs) and Major Adverse Events (MAEs).

Additional Information

Clinical Program Manager

Medtronic

Phone: 763-398-7000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60