PAD
Conditions
Brief summary
This is a prospective, single-arm, multi-center, international, open-label, clinical study.
Detailed description
The aim of the study is to assess the safety and efficacy of the Eximo Medical's B-Laser™ Atherectomy catheter in subjects with infrainguinal Peripheral Artery Disease (PAD).
Interventions
DEVICEB-Laser™ Atherectomy System
The B-Laser™ is indicated for use for atherectomy of infrainguinal stenoses
Sponsors
Eximo Medical Ltd.
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
1. Subject is ≥ 18 years old. 2. Subject is a candidate for atherectomy for infrainguinal peripheral artery disease. 3. Documented symptomatic atherosclerotic peripheral artery disease Rutherford Classification 2-4. 4. Subject has an infrainguinal target lesion(s) with any type of stenosis (naïve recurrent, or in-stent) estimated to be ≥70% based on CT angiogram or any other imaging modality. 5. Subject is capable and willing to comply with the scheduled follow up 6. Subject or appropriate legal surrogate is able and willing to sign a written Informed Consent Form (ICF). Intraoperative inclusion criteria (by fluoroscopy angiogram): 1. Target lesion has a stenosis estimated to be ≥70%. 2. In ATK subjects - at least one patent tibial run-off vessel into the foot \-
Exclusion criteria
1. Target lesion is in a vessel graft or synthetic graft. 2. Target lesion length \<1cm and \>15 cm (in ISR cases could be \>25cm). 3. Endovascular or surgical procedure in the target limb performed less than or equal to 30 days prior to the index procedure OR Planned endovascular or surgical procedure 30 days after the index procedure. 4. Intent to use other atherectomy device in the same procedure. 5. Evidence or history of intracranial or gastrointestinal bleeding, intracranial aneurysm, myocardial infarction or stroke within the past 2 months. 6. Evidence or history of aneurysm in the target vessel within the past 2 months. 7. History of bleeding diathesis, coagulopathy or inability to accept blood transfusions. 8. History of heparin-induced thrombocytopenia (HIT) or inability to tolerate antiplatelet medication(s), anticoagulation, or thrombolytic therapy. 9. Subjects requiring dialysis. 10. Known allergy to contrast agents or medications used to perform endovascular intervention that cannot be adequately pre-treated. 11. Serious illness that may affect subject compliance to protocol and 30-day follow-up. 12. Participating in another clinical study 13. Subject is pregnant or planning to become pregnant during the study period. 14. Life expectancy \< 12 months 15. Any planned amputation above the ankle. Intraoperative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute Technical Success | Perioperative | Reduction from baseline in residual diameter stenosis (%), prior to any adjunctive therapy, achieved by the B-Laser™ catheter A change (always a reduction) between two time points (baseline time-point and post B-Laser treatment time-point, both perioperative) is reported: * As assessed quantitatively by the core laboratory. * This endpoint will be met if the mean reduction in residual diameter stenosis is greater than 20%. * A greater reduction means better results. |
| Number of Participants With Freedom From 30 Days Major Adverse Events (MAEs) | 30 (+/-5) days post procedure | 1. Unplanned target limb amputation above the ankle 2. Clinically Driven Target Lesion Revascularization (CDTLR) 3. Cardiovascular related deaths * As adjudicated by the Clinical Event Committee (CEC). * This endpoint will be met if the freedom from MAE rate is greater than 85%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Lesions With Residual Stenosis by Angiography of ≤ 30% Post-procedure Including Any Adjunctive Therapy, With no Flow Limiting Dissection. | Perioperative | Number of Lesions with residual stenosis by angiography of ≤ 30% post-procedure including any adjunctive therapy, with no flow limiting dissection. \* As assessed quantitatively by the core laboratory. |
| PAD Measurements at the 30-day Visit Post-procedure Compared to Baseline (1) | 30 (+/-5) days post procedure | 1. Rutherford Classification: a doctor determined 7 stages scale (0= Asymptomatic, 6= Severe ischemic ulcers/frank gangrene) representing PAD progress, lower value = better outcome. Positive difference between time-points represents a clinical deterioration through time and vice versa. 2. Walking Impairment Questionnaire (WIQ): a patient fulfilled survey to grade physical ability representing PAD progress, has 3 sub-scales (walking speed, distance, climbing stairs), when the total score ranges between 0-100, higher value = better outcome. Positive difference between time-points represents a clinical improvement through time and vice versa. |
| Number of Lesions With Freedom From Clinically Significant [1] Device Related Adverse Events (AEs) Requiring Intervention in the Target Vessel | Perioperative and up to 30 (+/-5) days post procedure | 1. Perforation 2. Dissection 3. Distal embolization or in situ thrombus 4. Pseudoaneurysm * As adjudicated by the Clinical Event Committee (CEC). \[1\] Note: Clinically Significant AEs are defined as adverse events that REQUIRE any intervention,treatment or any hospitalization or its prolongation, in order to prevent death, persistent/significant disability/incapacity or congenital anomaly/birth defect. |
| Number of Lesions With Clinical Success at 30 Days | 30 (+/-5) days post procedure | Defined as \< 50% stenosis at the treated lesion, as assessed quantitatively by duplex ultrasound when the peak systolic velocity ratio is \< 2.5. \* As assessed quantitatively by the core laboratory. |
| PAD Measurements at the 30-day Visit Post-procedure Compared to Baseline (2) | 30 (+/-5) days post procedure | c) Ankle-Brachial Index (ABI): ankle/arm blood pressure ratio. Normal value ranges between 0.9-1.3. Under 0.9 index means blood has a difficult time getting to legs & feet; 0.4-0.9 indicates mild-moderate PAD; 0.4 and lower indicates severe PAD. Positive difference between time-points represents a clinical improvement through time and vice versa. |
| Number of Lesions With Freedom From Non-Clinically Significant [1] Device Related Adverse Events (AEs) in the Target Vessel | Perioperative and up to 30 (+/-5) days post procedure | 1. Perforation 2. Dissection 3. Distal embolization or in situ thrombus 4. Pseudoaneurysm * As adjudicated by the Clinical Event Committee (CEC). \[1\] Note: non-Clinically Significant AEs are defined as adverse events that DO NOT REQUIRE any intervention, treatment or any hospitalization or its prolongation, in order to prevent death, persistent/significant disability/incapacity or congenital anomaly/birth defect. |
Countries
Austria, Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| B-Laser™ Atherectomy System B-Laser™ Atherectomy System
B-Laser™ Atherectomy System: The B-Laser™ is indicated for use for atherectomy of infrainguinal stenoses | 97 |
| B-Laser™ Atherectomy System B-Laser™ Atherectomy System
B-Laser™ Atherectomy System: The B-Laser™ is indicated for use for atherectomy of infrainguinal stenoses | 107 |
| Total | 204 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Lost to Follow-up | 4 |
Baseline characteristics
| Characteristic | B-Laser™ Atherectomy System |
|---|---|
| ABI (Ankle Brachial Index) at baseline | 0.71 ratio STANDARD_DEVIATION 0.19 |
| Age, Continuous | 70.5 years |
| Baseline Calcification level at target lesion (by Core laboratory) mild/moderate | 55 Lesions |
| Baseline Calcification level at target lesion (by Core laboratory) no | 24 Lesions |
| Baseline Calcification level at target lesion (by Core laboratory) severe | 28 Lesions |
| Baseline Stenosis % at target lesion (by Core laboratory) Chronic total occlusion (stenosis 100%) | 23 Lesions |
| Baseline Stenosis % at target lesion (by Core laboratory) Stenosis ≤ 95% | 72 Lesions |
| Baseline Stenosis % at target lesion (by Core laboratory) Stenosis > 95% and ≤ 99% | 12 Lesions |
| Baseline Stenosis % at target lesion (by Core laboratory) | 85.7 % STANDARD_DEVIATION 12.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 13 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 | 0 Participants |
| Race (NIH/OMB) White | 83 Participants |
| Region of Enrollment Austria | 13 participants |
| Region of Enrollment Italy | 7 participants |
| Region of Enrollment United States | 77 participants |
| Rutherford class at baseline | 2.77 scores on a scale STANDARD_DEVIATION 0.6 |
| Sex: Female, Male Female | 46 Participants |
| Sex: Female, Male Male | 51 Participants |
| Target lesion length (by Core laboratory) | 5.4 cm |
| WIQ (Walking Impairment Questionnaire) at baseline | 0.23 scores on a scale STANDARD_DEVIATION 0.22 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 93 |
| other Total, other adverse events | 54 / 93 |
| serious Total, serious adverse events | 43 / 93 |
Outcome results
Primary
Acute Technical Success
Reduction from baseline in residual diameter stenosis (%), prior to any adjunctive therapy, achieved by the B-Laser™ catheter A change (always a reduction) between two time points (baseline time-point and post B-Laser treatment time-point, both perioperative) is reported: * As assessed quantitatively by the core laboratory. * This endpoint will be met if the mean reduction in residual diameter stenosis is greater than 20%. * A greater reduction means better results.
Time frame: Perioperative
Population: Unavailable angiographic data for primary efficacy endpoint analysis for 2 participants with 2 lesions out of the 97 participants with 109 lesions (these 2 were considered ITT and not PP).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B-Laser™ Atherectomy System | Acute Technical Success | 33.6 Change in RDS (%) | Standard Deviation 14.2 |
Primary
Number of Participants With Freedom From 30 Days Major Adverse Events (MAEs)
1. Unplanned target limb amputation above the ankle 2. Clinically Driven Target Lesion Revascularization (CDTLR) 3. Cardiovascular related deaths * As adjudicated by the Clinical Event Committee (CEC). * This endpoint will be met if the freedom from MAE rate is greater than 85%.
Time frame: 30 (+/-5) days post procedure
Population: 1 Cardiovascular related death was unrelated to the device per the CEC. Four participants out of the 97 with unavailable data: two were lost to follow-up before the 30-day visit was completed, and two others had their 30-day visit outside of the allowable window (day 16 and day 23).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B-Laser™ Atherectomy System | Number of Participants With Freedom From 30 Days Major Adverse Events (MAEs) | 92 Participants |
Secondary
Number of Lesions With Clinical Success at 30 Days
Defined as \< 50% stenosis at the treated lesion, as assessed quantitatively by duplex ultrasound when the peak systolic velocity ratio is \< 2.5. \* As assessed quantitatively by the core laboratory.
Time frame: 30 (+/-5) days post procedure
Population: Unavailable PSVR for 13 participants (14 lesions) from 95 participants (107 lesions): 5 participants (6 lesions) not diagnostic due to technical incompliance at exam; 3 participants (3 lesions) lost to follow-up; 1 participant (1 lesion) died; 4 participants (4 lesions), core lab could not calculate PSVR, yet were considered patent by absolute PSV.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| B-Laser™ Atherectomy System | Number of Lesions With Clinical Success at 30 Days | 90 lesions |
Secondary
Number of Lesions With Freedom From Clinically Significant [1] Device Related Adverse Events (AEs) Requiring Intervention in the Target Vessel
1. Perforation 2. Dissection 3. Distal embolization or in situ thrombus 4. Pseudoaneurysm * As adjudicated by the Clinical Event Committee (CEC). \[1\] Note: Clinically Significant AEs are defined as adverse events that REQUIRE any intervention,treatment or any hospitalization or its prolongation, in order to prevent death, persistent/significant disability/incapacity or congenital anomaly/birth defect.
Time frame: Perioperative and up to 30 (+/-5) days post procedure
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| B-Laser™ Atherectomy System | Number of Lesions With Freedom From Clinically Significant [1] Device Related Adverse Events (AEs) Requiring Intervention in the Target Vessel | 107 lesions |
Secondary
Number of Lesions With Freedom From Non-Clinically Significant [1] Device Related Adverse Events (AEs) in the Target Vessel
1. Perforation 2. Dissection 3. Distal embolization or in situ thrombus 4. Pseudoaneurysm * As adjudicated by the Clinical Event Committee (CEC). \[1\] Note: non-Clinically Significant AEs are defined as adverse events that DO NOT REQUIRE any intervention, treatment or any hospitalization or its prolongation, in order to prevent death, persistent/significant disability/incapacity or congenital anomaly/birth defect.
Time frame: Perioperative and up to 30 (+/-5) days post procedure
Population: All the 16 cases were type A (11) and B (5) dissections only. No perforations, major dissections, emboli or pseudoaneurysm.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| B-Laser™ Atherectomy System | Number of Lesions With Freedom From Non-Clinically Significant [1] Device Related Adverse Events (AEs) in the Target Vessel | 91 lesions |
Secondary
Number of Lesions With Residual Stenosis by Angiography of ≤ 30% Post-procedure Including Any Adjunctive Therapy, With no Flow Limiting Dissection.
Number of Lesions with residual stenosis by angiography of ≤ 30% post-procedure including any adjunctive therapy, with no flow limiting dissection. \* As assessed quantitatively by the core laboratory.
Time frame: Perioperative
Population: Unavailable data for primary efficacy endpoint analysis for 2 participants out of the 97.
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| B-Laser™ Atherectomy System | Number of Lesions With Residual Stenosis by Angiography of ≤ 30% Post-procedure Including Any Adjunctive Therapy, With no Flow Limiting Dissection. | Yes | 95 lesions |
| B-Laser™ Atherectomy System | Number of Lesions With Residual Stenosis by Angiography of ≤ 30% Post-procedure Including Any Adjunctive Therapy, With no Flow Limiting Dissection. | No | 12 lesions |
Secondary
PAD Measurements at the 30-day Visit Post-procedure Compared to Baseline (1)
1. Rutherford Classification: a doctor determined 7 stages scale (0= Asymptomatic, 6= Severe ischemic ulcers/frank gangrene) representing PAD progress, lower value = better outcome. Positive difference between time-points represents a clinical deterioration through time and vice versa. 2. Walking Impairment Questionnaire (WIQ): a patient fulfilled survey to grade physical ability representing PAD progress, has 3 sub-scales (walking speed, distance, climbing stairs), when the total score ranges between 0-100, higher value = better outcome. Positive difference between time-points represents a clinical improvement through time and vice versa.
Time frame: 30 (+/-5) days post procedure
Population: Only available data for comparison at the two time-points is presented for each parameter .
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B-Laser™ Atherectomy System | PAD Measurements at the 30-day Visit Post-procedure Compared to Baseline (1) | Rutherford difference (30 day post-procedure - BL) | -1.79 scores on a scale | Standard Error 1.22 |
| B-Laser™ Atherectomy System | PAD Measurements at the 30-day Visit Post-procedure Compared to Baseline (1) | WIQ difference (30 day post-procedure - BL) | 0.26 scores on a scale | Standard Error 0.28 |
Secondary
PAD Measurements at the 30-day Visit Post-procedure Compared to Baseline (2)
c) Ankle-Brachial Index (ABI): ankle/arm blood pressure ratio. Normal value ranges between 0.9-1.3. Under 0.9 index means blood has a difficult time getting to legs & feet; 0.4-0.9 indicates mild-moderate PAD; 0.4 and lower indicates severe PAD. Positive difference between time-points represents a clinical improvement through time and vice versa.
Time frame: 30 (+/-5) days post procedure
Population: Only available data for comparison at the two time-points is presented for each parameter .
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B-Laser™ Atherectomy System | PAD Measurements at the 30-day Visit Post-procedure Compared to Baseline (2) | 0.24 ratio | Standard Error 0.18 |
Post Hoc
Number of Lesions With 6-Month Patency [Not a Study Pre-specified Endpoint]
Defined as \< 50% stenosis at the treated lesion, as assessed quantitatively by duplex ultrasound when the peak systolic velocity ratio is \< 2.5. \* As assessed quantitatively by the core laboratory. This is not a study pre-specified endpoint.
Time frame: 6 months (+/-14 days) post procedure
Population: Unavailable PSVR for 14 participants (17 lesions) from 95 participants (107 lesions): 3 participants (4 lesions) not diagnostic due to technical incompliance at exam; 5 participants (5 lesions) lost to follow-up; 2 participants (3 lesions) died; 4 participants (5 lesions), core lab could not calculate PSVR.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| B-Laser™ Atherectomy System | Number of Lesions With 6-Month Patency [Not a Study Pre-specified Endpoint] | 77 lesions |
Post Hoc
Number of Participants With Freedom From 6 Months Major Adverse Events (MAEs) [Not a Study Pre-specified Endpoint]
1. Unplanned target limb amputation above the ankle 2. Clinically Driven Target Lesion Revascularization (CDTLR) 3. Cardiovascular related deaths * As adjudicated by the Clinical Event Committee (CEC).
Time frame: 6 months (+/-14 days) post procedure
Population: 3 CD-TLRs were possibly related to device \& definitely related to index procedure, per CEC. 8 participants out of total 97 with unavailable data: 3 subjects were lost to follow-up before 6-month visit was completed, 1 subject died before 6-month visit, and 3 other subjects had their 6-month visit outside of the allowable window (before Day 166).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| B-Laser™ Atherectomy System | Number of Participants With Freedom From 6 Months Major Adverse Events (MAEs) [Not a Study Pre-specified Endpoint] | 86 Participants |
Post Hoc
PAD Measurements at the 6-month Visit Post-procedure Compared to Baseline [Not a Study Pre-specified Endpoint] (1)
1. Rutherford Classification: a doctor determined 7 stages scale (0= Asymptomatic, 6= Severe ischemic ulcers/frank gangrene) representing PAD progress, lower value = better outcome. Positive difference between time-points represents a clinical deterioration through time and vice versa. 2. Walking Impairment Questionnaire (WIQ): a patient fulfilled survey to grade physical ability representing PAD progress, has 3 sub-scales (walking speed, distance, climbing stairs), when the total score ranges between 0-100, higher value = better outcome. Positive difference between time-points represents a clinical improvement through time and vice versa.
Time frame: 6-month (+/-14 days) post-procedure
Population: Only available data for comparison at the two time-points is presented for each parameter .
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B-Laser™ Atherectomy System | PAD Measurements at the 6-month Visit Post-procedure Compared to Baseline [Not a Study Pre-specified Endpoint] (1) | Rutherford difference (6 month post-procedure -BL) | -2.02 score on a scale | Standard Error 1.12 |
| B-Laser™ Atherectomy System | PAD Measurements at the 6-month Visit Post-procedure Compared to Baseline [Not a Study Pre-specified Endpoint] (1) | WIQ difference (6 month post-procedure -BL) | 0.25 score on a scale | Standard Error 0.3 |
Post Hoc
PAD Measurements at the 6-month Visit Post-procedure Compared to Baseline [Not a Study Pre-specified Endpoint] (2)
c) Ankle-Brachial Index (ABI): ankle/arm blood pressure ratio. Normal value ranges between 0.9-1.3. Under 0.9 index means blood has a difficult time getting to legs & feet; 0.4-0.9 indicates mild-moderate PAD; 0.4 and lower indicates severe PAD. Positive difference between time-points represents a clinical improvement through time and vice versa.
Time frame: 6-month (+/-14 days) post-procedure
Population: Only available data for comparison at the two time-points is presented for each parameter .
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| B-Laser™ Atherectomy System | PAD Measurements at the 6-month Visit Post-procedure Compared to Baseline [Not a Study Pre-specified Endpoint] (2) | 0.17 ratio | Standard Error 0.28 |