Peripheral Arterial Disease
Conditions
Keywords
PAD, PVD, SFA stent
Brief summary
To demonstrate that the BioMimics 3D Stent System meets the performance goals defined by VIVA Physicians, Inc. for the safety and effectiveness of Nitinol stents used in the treatment of symptomatic disease of the femoropopliteal artery. It is a prospective, single-arm, multicenter clinical trial.
Detailed description
The BioMimics 3D stent is intended to improve luminal diameter in the treatment of symptomatic de-novo, obstructive or occlusive lesions in native femoropopliteal arteries with reference vessel diameters ranging from 4.0 - 6.0 mm. Subjects with symptomatic atherosclerotic disease of the femoropopliteal artery who comply with all study eligibility criteria may be considered for enrollment.
Interventions
Femoropopliteal stenting
Sponsors
ClinLogix. LLC
Yale Cardiovascular Research Group
Massachusetts General Hospital
Veryan Medical Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Symptomatic peripheral arterial disease (PAD) of the lower extremities requiring intervention to relieve de novo obstruction or occlusion of the native femoropopliteal artery. * PAD classified as Rutherford clinical category 2, 3 or 4. * Resting ankle-brachial index (ABI) of ≤0.90 (or ≤0.75 after exercise of the target limb) or angiographic or DUS evidence of \>/= 60%. * Single or multiple stenotic or occlusive lesions within the native femoropopliteal artery (target lesions) that can be crossed with a guidewire and fully dilated. * Single or multiple target lesions must be covered by a single stent or two overlapping stents. * Target lesion(s) eligible for treatment at least 1 cm distal to the origin of the deep femoral artery and at least 3 cm above the bottom of the femur. * Target lesion(s) reference vessel diameter is between 4.0 mm and 6.0 mm. * Single or multiple target lesions measure ≥40 mm to ≤140 mm in overall length, with ≥60% diameter stenosis by operator's visual estimate. * Patent popliteal artery (no stenosis ≥50%) distal to the treated segment. * At least one patent infrapopliteal vessel (\<50% stenosis) with run-off to the ankle.
Exclusion criteria
* Iliac stent in target limb that has required re-intervention within 12 months prior to index. * Target vessel that has been treated with bypass surgery. * PAD classified as Rutherford clinical category 0, 1, 5 or 6. * Known coagulopathy or has bleeding diatheses, thrombocytopenia with platelet count less than 100,000/microliter or INR \>1.8. * Stroke diagnosis within 3 months prior to enrollment. * History of unstable angina or myocardial infarction within 60 days prior to enrollment. * Thrombolysis within 72 hours prior to the index procedure. * Acute or chronic renal disease (e.g., as measured by a serum creatinine of \>2.5 mg/dL or \>220 umol/L), or on peritoneal or hemodialysis. * Significant disease or obstruction (≥50%) of the inflow tract that has not been successfully treated at the time of the index procedure (success measured as ≤30% residual stenosis, without complication). * No patent (≥50% stenosis) outflow vessel providing run-off to the ankle. * Target lesion(s) requires percutaneous interventional treatment, beyond standard balloon angioplasty alone, prior to placement of the study stent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Endpoint (Freedom From a Composite of Major Adverse Events (MAE) | 30 days | Freedom from a composite of major adverse events (MAE) comprising death, any major amputation performed on the target limb or clinically-driven target lesion revascularization (TLR) through 30 days. |
| Primary Effectiveness Endpoint (Primary Stent Patency Rate) | 12 months | The primary effectiveness endpoint of the MIMICS-2 Study was defined as the primary stent patency rate at 12 months. Patency was defined as no significant reduction in luminal diameter (\< 50% diameter stenosis) since the index procedure. Loss of patency was determined by an independent core laboratory when the peak systolic velocity ratio (PSVR) exceeds 2.0, or where angiography revealed \> 50% diameter stenosis, or where the subject had a CDTLR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events | 36 Months | Overall rate and incidence of type of serious adverse events from Day 0 through completion of Study follow-up at Month 36. |
| Technical Success | Procedural (at end of index procedure) | Percentage of subjects in which a final result of ≤50% residual diameter stenosis (in-stent) was achieved at index procedure |
| Primary Stent Patency | Months 12 & 24 | Determined at Months-12 and 24 using values of: PSVR \>2.0, \>2.4; \>2.5; and \>3.5, each to indicate loss of patency on duplex ultrasound or where angiography reveals \>50% diameter stenosis or where the subject undergoes clinically-driven TLR. Further analysis of the patency data purely using a reference PSVR of \>2.4, \>2.5 and \>3.5 was not feasible from the data that was collected. |
| Number of Participants With Improvement of Rutherford Clinical Category by 1 or More | Baseline, Day 30, Months 12 & 24 | Comparison of Rutherford Clinical Category measured at Baseline, Day 30, Months 12 and 24. Categories 0 - Asymptomatic 1. \- Mild claudication 2. \- Moderate claudication 3. \- Severe claudication 4. \- Ischemic rest pain 5. \- Minor tissue loss 6. \- Major tissue loss |
| Secondary Safety (Overall MAE Rate at 30 Days) | 30 Days | Contribution of individual MAE rates for death, major amputation performed on the target limb and clinically-driven target lesion revascularization to the overall MAE rate at 30 days. |
| Functional Outcome (Ankle Brachial Index (ABI) Measurement) | Baseline, Day 30, Months 12 & 24 | Comparison of the ankle brachial index (ABI) measurement at Baseline, within 30 days after index procedure, then at Months 12 and 24. |
| Change of Walking Impairment Questionnaire Score | Baseline, Day 30, Months 12 & 24 | Comparison of the Walking Impairment Questionnaire at Baseline, within 30 days after index procedure, then at Months 12 and 24. The WIQ consists of 3 primary categories assessing walking distance, stair-climbing, and walking speed, as previously described. Individuals are asked to rate the degree of difficulty of various activities with responses ranging from 0 (unable) to 4 (none). |
| Number of Participants With Freedom From Stent Fracture | Months 12, 24 & 36 | Stent integrity measured as freedom from fracture, defined as clear interruption of a stent strut observed in a minimum of two projections, determined by core lab examination of X-rays taken with the leg in extension at 12, 24 and 36 Months. |
| Clinical Outcome (Six-Minute Walk Test) | Baseline, Day 30, Months 12 & 24 | Comparison of measured at Baseline, Day 30, Months 12 and 24 (subgroup of US investigational sites only). |
| Long Term Safety (Overall MAE Rate at Month 12) | 12 months | Overall MAE rate at Month 12 and contribution of individual event rates to the overall MAE. |
Countries
Germany, Japan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BioMimics 3D Stent Implantation of BioMimics 3D nitinol stent using the BioMimics 3D Stent System | 271 |
| Total | 271 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 24 |
| Overall Study | Lost to Follow-up | 18 |
| Overall Study | Other | 1 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Withdrawal by Subject | 16 |
Baseline characteristics
| Characteristic | BioMimics 3D Stent |
|---|---|
| Age, Continuous | 68.4 years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 253 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 31 Participants |
| Race (NIH/OMB) Black or African American | 16 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 | 9 Participants |
| Race (NIH/OMB) White | 215 Participants |
| Sex: Female, Male Female | 91 Participants |
| Sex: Female, Male Male | 180 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 24 / 271 |
| other Total, other adverse events | 177 / 271 |
| serious Total, serious adverse events | 164 / 271 |
Outcome results
Primary
Primary Effectiveness Endpoint (Primary Stent Patency Rate)
The primary effectiveness endpoint of the MIMICS-2 Study was defined as the primary stent patency rate at 12 months. Patency was defined as no significant reduction in luminal diameter (\< 50% diameter stenosis) since the index procedure. Loss of patency was determined by an independent core laboratory when the peak systolic velocity ratio (PSVR) exceeds 2.0, or where angiography revealed \> 50% diameter stenosis, or where the subject had a CDTLR.
Time frame: 12 months
Population: Subjects were included in analysis population if they had imaging data qualifying as a 12m visit and/or subjects without imaging data who experienced a CDTLR through 12 months. Additionally, if a subject is missing stent patency status at the 12m window but found to be patent at a later out-of-window date, subject was considered patent at 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BioMimics 3D Stent | Primary Effectiveness Endpoint (Primary Stent Patency Rate) | 182 Participants |
Primary
Primary Safety Endpoint (Freedom From a Composite of Major Adverse Events (MAE)
Freedom from a composite of major adverse events (MAE) comprising death, any major amputation performed on the target limb or clinically-driven target lesion revascularization (TLR) through 30 days.
Time frame: 30 days
Population: Subjects with available 30 day follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BioMimics 3D Stent | Primary Safety Endpoint (Freedom From a Composite of Major Adverse Events (MAE) | 268 Participants |
Secondary
Change of Walking Impairment Questionnaire Score
Comparison of the Walking Impairment Questionnaire at Baseline, within 30 days after index procedure, then at Months 12 and 24. The WIQ consists of 3 primary categories assessing walking distance, stair-climbing, and walking speed, as previously described. Individuals are asked to rate the degree of difficulty of various activities with responses ranging from 0 (unable) to 4 (none).
Time frame: Baseline, Day 30, Months 12 & 24
Population: Walking Impairment Questionnaire score at Baseline, within 30 days after index procedure, then at Months 12 and 24.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BioMimics 3D Stent | Change of Walking Impairment Questionnaire Score | Baseline WIQ score | 0.28 scores on a scale | Standard Deviation 0.24 |
| BioMimics 3D Stent | Change of Walking Impairment Questionnaire Score | 30 Days WIQ score | 0.58 scores on a scale | Standard Deviation 0.32 |
| BioMimics 3D Stent | Change of Walking Impairment Questionnaire Score | 12 Months WIQ score | 0.58 scores on a scale | Standard Deviation 0.31 |
| BioMimics 3D Stent | Change of Walking Impairment Questionnaire Score | 24 Months WIQ score | 0.56 scores on a scale | Standard Deviation 0.31 |
Secondary
Clinical Outcome (Six-Minute Walk Test)
Comparison of measured at Baseline, Day 30, Months 12 and 24 (subgroup of US investigational sites only).
Time frame: Baseline, Day 30, Months 12 & 24
Population: Number of participants analysed changed over the time period
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BioMimics 3D Stent | Clinical Outcome (Six-Minute Walk Test) | Baseline | 230 yards | Standard Deviation 162 |
| BioMimics 3D Stent | Clinical Outcome (Six-Minute Walk Test) | 30 Days | 349 yards | Standard Deviation 221 |
| BioMimics 3D Stent | Clinical Outcome (Six-Minute Walk Test) | 12 Months | 278 yards | Standard Deviation 143 |
| BioMimics 3D Stent | Clinical Outcome (Six-Minute Walk Test) | 24 Months | 405 yards | Standard Deviation 140 |
Secondary
Functional Outcome (Ankle Brachial Index (ABI) Measurement)
Comparison of the ankle brachial index (ABI) measurement at Baseline, within 30 days after index procedure, then at Months 12 and 24.
Time frame: Baseline, Day 30, Months 12 & 24
Population: Number of participants assessed for ABI index measurement at Baseline, within 30 days after index procedure, then at Months 12 and 24.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BioMimics 3D Stent | Functional Outcome (Ankle Brachial Index (ABI) Measurement) | ABI at Baseline | 0.70 ABI | Standard Deviation 0.2 |
| BioMimics 3D Stent | Functional Outcome (Ankle Brachial Index (ABI) Measurement) | ABI at 30 Days | 0.98 ABI | Standard Deviation 0.16 |
| BioMimics 3D Stent | Functional Outcome (Ankle Brachial Index (ABI) Measurement) | ABI at 12 Months | 0.92 ABI | Standard Deviation 0.19 |
| BioMimics 3D Stent | Functional Outcome (Ankle Brachial Index (ABI) Measurement) | ABI at 24 Months | 0.94 ABI | Standard Deviation 0.2 |
Secondary
Long Term Safety (Overall MAE Rate at Month 12)
Overall MAE rate at Month 12 and contribution of individual event rates to the overall MAE.
Time frame: 12 months
Population: Subjects are included in the analysis population if (i) they have sufficient follow-up (at least 12 months less 30 days), or (ii) they have had the event of interest (each event is considered separately).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BioMimics 3D Stent | Long Term Safety (Overall MAE Rate at Month 12) | Freedom from MAE | 226 Participants |
| BioMimics 3D Stent | Long Term Safety (Overall MAE Rate at Month 12) | Freedom from Death | 257 Participants |
| BioMimics 3D Stent | Long Term Safety (Overall MAE Rate at Month 12) | Freedom from Major Amputation | 258 Participants |
| BioMimics 3D Stent | Long Term Safety (Overall MAE Rate at Month 12) | Freedom from CD-TLR | 227 Participants |
Secondary
Number of Participants With Freedom From Stent Fracture
Stent integrity measured as freedom from fracture, defined as clear interruption of a stent strut observed in a minimum of two projections, determined by core lab examination of X-rays taken with the leg in extension at 12, 24 and 36 Months.
Time frame: Months 12, 24 & 36
Population: Number of participants with no fracture in study stent at 12, 24 and 36 Months assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BioMimics 3D Stent | Number of Participants With Freedom From Stent Fracture | Freedom from stent fracture at 36 Months | 102 Participants |
| BioMimics 3D Stent | Number of Participants With Freedom From Stent Fracture | Freedom from stent fracture at 12 Months | 229 Participants |
| BioMimics 3D Stent | Number of Participants With Freedom From Stent Fracture | Freedom from stent fracture at 24 Months | 204 Participants |
Secondary
Number of Participants With Improvement of Rutherford Clinical Category by 1 or More
Comparison of Rutherford Clinical Category measured at Baseline, Day 30, Months 12 and 24. Categories 0 - Asymptomatic 1. \- Mild claudication 2. \- Moderate claudication 3. \- Severe claudication 4. \- Ischemic rest pain 5. \- Minor tissue loss 6. \- Major tissue loss
Time frame: Baseline, Day 30, Months 12 & 24
Population: Number of participants participating in the study changed at 30 Days, 12 Months and 24 Months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BioMimics 3D Stent | Number of Participants With Improvement of Rutherford Clinical Category by 1 or More | Improvement of Rutherford Category of 1 or more at 30 Days | 233 Participants |
| BioMimics 3D Stent | Number of Participants With Improvement of Rutherford Clinical Category by 1 or More | Improvement of Rutherford Category of 1 or more at 12 Months | 216 Participants |
| BioMimics 3D Stent | Number of Participants With Improvement of Rutherford Clinical Category by 1 or More | Improvement of Rutherford Category of 1 or more at 24 Months | 195 Participants |
Secondary
Number of Participants With Serious Adverse Events
Overall rate and incidence of type of serious adverse events from Day 0 through completion of Study follow-up at Month 36.
Time frame: 36 Months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BioMimics 3D Stent | Number of Participants With Serious Adverse Events | total number of participants | 271 Participants |
| BioMimics 3D Stent | Number of Participants With Serious Adverse Events | All SAE (In-hospital) | 13 Participants |
| BioMimics 3D Stent | Number of Participants With Serious Adverse Events | All SAE (30 Days) | 26 Participants |
| BioMimics 3D Stent | Number of Participants With Serious Adverse Events | All SAE (12 Months) | 114 Participants |
| BioMimics 3D Stent | Number of Participants With Serious Adverse Events | All SAE (24 Months) | 146 Participants |
| BioMimics 3D Stent | Number of Participants With Serious Adverse Events | All SAE (36 Months) | 164 Participants |
Secondary
Primary Stent Patency
Determined at Months-12 and 24 using values of: PSVR \>2.0, \>2.4; \>2.5; and \>3.5, each to indicate loss of patency on duplex ultrasound or where angiography reveals \>50% diameter stenosis or where the subject undergoes clinically-driven TLR. Further analysis of the patency data purely using a reference PSVR of \>2.4, \>2.5 and \>3.5 was not feasible from the data that was collected.
Time frame: Months 12 & 24
Population: Relevant data was not collected to provide the outcome analysis
Secondary
Secondary Safety (Overall MAE Rate at 30 Days)
Contribution of individual MAE rates for death, major amputation performed on the target limb and clinically-driven target lesion revascularization to the overall MAE rate at 30 days.
Time frame: 30 Days
Population: Subjects with available 30 day follow-up
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BioMimics 3D Stent | Secondary Safety (Overall MAE Rate at 30 Days) | Freedom from Death | 269 Participants |
| BioMimics 3D Stent | Secondary Safety (Overall MAE Rate at 30 Days) | Freedom from Major Amputation | 269 Participants |
| BioMimics 3D Stent | Secondary Safety (Overall MAE Rate at 30 Days) | Freedom from CD-TLR | 268 Participants |
Secondary
Technical Success
Percentage of subjects in which a final result of ≤50% residual diameter stenosis (in-stent) was achieved at index procedure
Time frame: Procedural (at end of index procedure)
Population: Subjects with available baseline angiography
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BioMimics 3D Stent | Technical Success | 269 Participants |