Peripheral Vascular Disease
Conditions
Keywords
atherosclerotic stenosis, occlusions, Superficial Femoral Artery, SFA
Brief summary
OSPREY is a multi-center, single arm, non-randomized, prospective clinical trial. Subjects will undergo a superficial femoral artery (SFA) stent procedure using the Misago™ Peripheral Self Expanding stent once all of the inclusion and none of the exclusion criteria are met. The stent efficacy and safety will be evaluated immediately post procedure, and at 30 days, 6, 12, 24, and 36 months post procedure. A subject is considered enrolled into the OSPREY study after he/she signs the informed consent and meets all inclusion/exclusion criteria. The study objectives are to demonstrate that efficacy and safety of this novel stent design are not inferior to historical Percutaneous Transluminal Angioplasty (PTA) and stent outcomes and meet the performance goals as published in the objective performance goals by Rocha-Singh, et al. This is a multi-center, single arm, non-randomized, prospective clinical trial of the Misago™ Self-Expanding Stent System for the treatment of atherosclerotic stenosis and occlusions of the SFA. The primary endpoint of stent patency will be evaluated at 12 months.
Interventions
DEVICEMisago™ Self-Expanding Stent System
Transcatheter placement of an intravascular stent(s)
Sponsors
ClinLogix. LLC
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Terumo Medical Corporation
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
Yes
Inclusion criteria
Pre-procedure: 1. Female or male age greater than or equal to 18 years and of legal consent. 2. Subjects must be willing to comply with the specified follow-up evaluation schedule. 3. Informed consent (signed and dated) prior to any study-related evaluation or procedures. 4. Symptomatic leg ischemia without tissue loss by Rutherford classification (category 2, 3 or 4). 5. Resting ABI of \<0.9, or abnormal exercise ABI. 6. De novo lesion(s) (one or multiple lesions) with \>50% stenosis, or occlusion which require treatment, and a total lesion length of \>40 mm and \<150 mm of the above-the-knee SFA in one limb. The target lesion should be treatable with no more than two overlapping stents, minimizing the stent overlap up to 10 mm (by visual estimate). 7. All lesions are at least 3 cm above the knee joint, defined as the distal end of the femur at the knee joint, and at least 2 cm distal to the origin of the profunda artery. 8. Reference vessel diameter of \>4.0 mm and \<7.0 mm. 9. Target lesion length of \> 40 mm and \<150 mm. 10. Patent popliteal artery (no stenosis \> 50%) and at least one patent tibioperoneal run-off vessel with \< 50% stenosis confirmed by angiography within 30 days of enrollment.
Exclusion criteria
1. Pre-existing autoimmune disease. 2. Pre-existing terminal illness with life expectancy of less than three (3) years. 3. Participation in another investigational device or therapeutic intervention trial within the past three (3) months. 4. Previous enrollment in this study. 5. Previous bypass surgery or stenting in the SFA or distally. 6. Scheduled for a staged procedure to treat lesions within the aorta or run-off after enrollment. 7. Co-existing aneurysmal disease of the aorta, iliac artery, SFA, or popliteal arteries requiring treatment. 8. Any inflow disease of the ipsilateral pelvic arteries (more than 50 percent stenosis or occlusion) that has not been treated prior to enrollment (Treatment of iliac arteries before SFA intervention is permitted, except for common femoral stenosis). 9. A recent (\< 6 week) history of clinically significant gastrointestinal bleeding, major surgery, myocardial infarction or untreated coagulopathy. 10. Known sensitivity or allergy to aspirin, radiographic contrast agents (that cannot be pre-treated adequately), nitinol, gold, or both heparin and bivalirudin. 11. Angiographic evidence of acute thrombus. 12. Sudden worsening of symptoms in the last 30 days. 13. Subjects with acute/chronic renal dysfunction or estimated glomerular filtration rate (eGFR) \<30 ml/min. Chronic hemodialysis subjects are not eligible for this protocol. 14. Severe calcification or excessive tortuosity at target lesion. 15. Subjects unable to tolerate anticoagulant therapy or antiplatelet therapy. 16. Women who are currently pregnant. (A negative pregnancy test for female subjects of child bearing potential is required). 17. The target lesion(s) cannot be successfully crossed with a guide wire.\* 18. Lower extremity deep venous thrombosis in the study limb within the prior 30 days. 19. Chronic venous disease with active or recent (\< 30 day) skin ulceration. 20. Known or suspected active systemic infection. 21. Two (2) months previous history of non-hemorrhagic stroke and or history of hemorrhagic stroke. 22. Treatment that requires access via upper extremity, popliteal artery, or pedal artery. 23. Evidence of severe or uncontrolled systemic disease of any condition which in the investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol. 24. Use of re-entry, ablative, or atherectomy devices to cross the lesion.\*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Effectiveness Endpoint | 12 Months post-procedure | The primary effectiveness endpoint was defined as stent patency at 12 months as evidenced by absence of TLR and a peak systolic velocity ratio \< 2.0 from DUS obtained within the 12 months visit window. |
| Primary Safety Endpoint | 30 days post-procedure | The primary safety endpoint for this study was freedom from major adverse events (MAE) at 30 days post-procedure. MAE was defined as TLR, amputation of the treated limb, or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Target Lesion Revascularization | 12 Months post-procedure | The occurrence of clinically driven Target Lesion Revascularization (TLR) was measured at 12 months post-procedure. Clinically driven defined as: * More than 50 percent stenosis with worsening symptoms, OR * More than 70 percent stenosis without symptoms |
| Device Related Peri-Procedural Complications | Prior to Hosptial Discharge | Peri-procedural (prior to discharge) measure of success (i.e., patency and none of the following: death, stroke, MI, embolization, thrombosis, and occlusion) |
| Technical Success | Intra-procedure | Technical Success defined by the following conditions: * Successful delivery of the stent at the lesion site * Stent(s) successfully deployed in lesion with adequate lesion coverage |
| Primary Effectiveness Endpoint in Modified Intent-to-Treat (mITT) Cohort | 12 Months post-procedure | Primary effectiveness endpoint was defined as absence of TLR and stent patency at 12 months as evidenced by a peak systolic velocity ratio \< 2.0 from DUS obtained within the 12 months visit window. Because patency beyond the 12 months visit window may be considered as patency at 12 months, the out-of-window patency is imputed as treatment success. The modified intention to treat (mITT) cohort had 226 subjects (excluded subjects with unknown primary effectiveness endpoint). |
| Clinical Success | 30 days post-procedure | Clinical success defined as: relief or improvement from baseline symptoms as measured by the Rutherford score for chronic limb ischemia at 30 days as compared to baseline |
| Major Adverse Events (MAEs) Through 12 Months Post-procedure | 12 Months post-procedure | The incidence of MAEs occurring within 12 months of the procedure. MAE is defined as target lesion revascularization (TLR), amputation of the treated limb, or death. |
| Stent Fracture at 12 Months | 12 Months post-procedure | Occurrence of stent fracture as determined by core laboratory analysis |
| Procedural Success | Intra-procedure | Procedural success defined as: attainment of \< 30% residual stenosis of the target lesion and no peri-procedural complications defined as: death, stroke, myocardial infarction, emergent surgical revascularization, significant distal embolization in target limb, and thrombosis of target vessel |
| Primary Effectiveness Endpoint Using a Peak Systolic Velocity Ratio of ≤ 2.4 (i.e., Modified VIVA Criteria) in the mITT Cohort | 12 Months post-procedure | The primary effectiveness endpoint was defined as absence of TLR and stent patency at 12 months as evidenced by a peak systolic velocity ratio \< 2.0 from duplex ultrasound. Additional considerations were made using a more contemporary approach to evaluate stent patency using a peak systolic velocity ratio (PSVR) ≤ 2.4 (i.e., modified VIVA criteria). This outcome evaluated the modified intent-to-treat (mITT) cohort comprised of 226 subjects (excluded subjects with unknown primary effectiveness endpoint) |
Countries
United States
Participant flow
Pre-assignment details
A total of 261 subjects were enrolled in the pivotal study cohort. An additional 15 subjects were implanted with a single, 150mm stent as part of a long length stent (LL) sub-study. The LL sub-study included safety data through 30 days post-procedure and was analyzed separately from the pivotal study cohort.
Participants by arm
| Arm | Count |
|---|---|
| Misago™ Self-Expanding Stent System Misago™ Self-Expanding Stent System: Transcatheter placement of an intravascular stent(s) | 261 |
| Long Length (150mm) Misago™ Self-Expanding Stent System Misago™ Self-Expanding Stent System: Transcatheter placement of a single, 150mm intravascular stent | 15 |
| Total | 276 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 8 | 0 |
| Overall Study | Lost to Follow-up | 6 | 0 |
| Overall Study | Missed 12 Month Visit | 7 | 0 |
Baseline characteristics
| Characteristic | Long Length (150mm) Misago™ Self-Expanding Stent System | Total | Misago™ Self-Expanding Stent System |
|---|---|---|---|
| Age, Continuous | 70.7 years STANDARD_DEVIATION 10.9 | NA years | 69.3 years STANDARD_DEVIATION 10 |
| Region of Enrollment Japan | 0 participants | 50 participants | 50 participants |
| Region of Enrollment Korea, Republic of | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Taiwan | 0 participants | 9 participants | 9 participants |
| Region of Enrollment United States | 15 participants | 216 participants | 201 participants |
| Sex: Female, Male Female | 8 Participants | 100 Participants | 92 Participants |
| Sex: Female, Male Male | 7 Participants | 176 Participants | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 167 / 261 | 7 / 15 |
| serious Total, serious adverse events | 135 / 261 | 1 / 15 |
Outcome results
Primary
Primary Effectiveness Endpoint
The primary effectiveness endpoint was defined as stent patency at 12 months as evidenced by absence of TLR and a peak systolic velocity ratio \< 2.0 from DUS obtained within the 12 months visit window.
Time frame: 12 Months post-procedure
Population: Analysis comprised of 261 subjects enrolled in pivotal trial and missing data imputed as loss of patency under the intention-to-treat (ITT) analysis. Study success was based on the proportion of patients with stent patency when tested against a performance goal of 66% using the lower bound of the 95% confidence interval.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Randomized | Primary Effectiveness Endpoint | 54.0 percentage of stent patency |
Primary
Primary Safety Endpoint
The primary safety endpoint for this study was freedom from major adverse events (MAE) at 30 days post-procedure. MAE was defined as TLR, amputation of the treated limb, or death.
Time frame: 30 days post-procedure
Population: Study success was based on the proportion of patients with freedom from MAE at 30 days post-procedure when tested against a performance goal of 88% using the lower bound of the 95% confidence interval. In both cohorts, the lower confidence interval exceeded the prespecified performance goal indicating the study met its primary safety endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Randomized | Primary Safety Endpoint | 99.2 percentage of subjects without a MAE |
| Long Length Stent Sub-Study Cohort | Primary Safety Endpoint | 100 percentage of subjects without a MAE |
Secondary
Clinical Success
Clinical success defined as: relief or improvement from baseline symptoms as measured by the Rutherford score for chronic limb ischemia at 30 days as compared to baseline
Time frame: 30 days post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Randomized | Clinical Success | 90.0 percentage of subjects with success |
| Long Length Stent Sub-Study Cohort | Clinical Success | 92.9 percentage of subjects with success |
Secondary
Device Related Peri-Procedural Complications
Peri-procedural (prior to discharge) measure of success (i.e., patency and none of the following: death, stroke, MI, embolization, thrombosis, and occlusion)
Time frame: Prior to Hosptial Discharge
Population: All enrolled participants evaluated prior to hospital discharge
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Randomized | Device Related Peri-Procedural Complications | 2.3 percentage of subjects with event |
Secondary
Major Adverse Events (MAEs) Through 12 Months Post-procedure
The incidence of MAEs occurring within 12 months of the procedure. MAE is defined as target lesion revascularization (TLR), amputation of the treated limb, or death.
Time frame: 12 Months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Randomized | Major Adverse Events (MAEs) Through 12 Months Post-procedure | 16.1 percentage of subjects with event |
Secondary
Occurrence of Target Lesion Revascularization
The occurrence of clinically driven Target Lesion Revascularization (TLR) was measured at 12 months post-procedure. Clinically driven defined as: * More than 50 percent stenosis with worsening symptoms, OR * More than 70 percent stenosis without symptoms
Time frame: 12 Months post-procedure
Population: Comprised of all subjects enrolled in the pivotal OSPREY trial (N=261)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Randomized | Occurrence of Target Lesion Revascularization | 13.0 percentage of subjects with TLR |
Secondary
Primary Effectiveness Endpoint in Modified Intent-to-Treat (mITT) Cohort
Primary effectiveness endpoint was defined as absence of TLR and stent patency at 12 months as evidenced by a peak systolic velocity ratio \< 2.0 from DUS obtained within the 12 months visit window. Because patency beyond the 12 months visit window may be considered as patency at 12 months, the out-of-window patency is imputed as treatment success. The modified intention to treat (mITT) cohort had 226 subjects (excluded subjects with unknown primary effectiveness endpoint).
Time frame: 12 Months post-procedure
Population: The modified intention to treat (mITT) cohort had 226 subjects (excluded subjects with unknown primary effectiveness endpoint).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Randomized | Primary Effectiveness Endpoint in Modified Intent-to-Treat (mITT) Cohort | 62.4 percentage of stent patency |
Secondary
Primary Effectiveness Endpoint Using a Peak Systolic Velocity Ratio of ≤ 2.4 (i.e., Modified VIVA Criteria) in the mITT Cohort
The primary effectiveness endpoint was defined as absence of TLR and stent patency at 12 months as evidenced by a peak systolic velocity ratio \< 2.0 from duplex ultrasound. Additional considerations were made using a more contemporary approach to evaluate stent patency using a peak systolic velocity ratio (PSVR) ≤ 2.4 (i.e., modified VIVA criteria). This outcome evaluated the modified intent-to-treat (mITT) cohort comprised of 226 subjects (excluded subjects with unknown primary effectiveness endpoint)
Time frame: 12 Months post-procedure
Population: Analysis uses a more contemporary approach to evaluate primary stent patency using a peak systolic velocity ratio ≤ 2.4 (modified VIVA criteria). Because patency beyond the 12 months visit window may be considered as patency at 12 months, the out-of-window patency is imputed as treatment success in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Randomized | Primary Effectiveness Endpoint Using a Peak Systolic Velocity Ratio of ≤ 2.4 (i.e., Modified VIVA Criteria) in the mITT Cohort | 69.9 percentage of stent patency |
Secondary
Procedural Success
Procedural success defined as: attainment of \< 30% residual stenosis of the target lesion and no peri-procedural complications defined as: death, stroke, myocardial infarction, emergent surgical revascularization, significant distal embolization in target limb, and thrombosis of target vessel
Time frame: Intra-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Randomized | Procedural Success | 93.5 percentage of subjects with success |
| Long Length Stent Sub-Study Cohort | Procedural Success | 100 percentage of subjects with success |
Secondary
Stent Fracture at 12 Months
Occurrence of stent fracture as determined by core laboratory analysis
Time frame: 12 Months post-procedure
Population: X-rays for 324 stents (234 subjects) were available for analysis by the angiographic core laboratory to evaluate stent fractures at 12 months post-procedure. One stent fracture was caused by a physician during a non-study peripheral intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Randomized | Stent Fracture at 12 Months | 0.9 percentage of fracture occurrence |
Secondary
Technical Success
Technical Success defined by the following conditions: * Successful delivery of the stent at the lesion site * Stent(s) successfully deployed in lesion with adequate lesion coverage
Time frame: Intra-procedure
Population: All subjects enrolled in pivotal trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Non-Randomized | Technical Success | 100 percentage of subjects with success |
| Long Length Stent Sub-Study Cohort | Technical Success | 93.3 percentage of subjects with success |