Superficial Femoral Artery Disease
Conditions
Keywords
Superficial Femoral Artery, Nitinol Self-Expandable Stent System
Brief summary
A multi-center, non-randomized, single-arm, prospective trial evaluating the safety and effectiveness of the S.M.A.R.T.™ Nitinol Stent System implantation in approximately 250 patients with obstructive superficial femoral artery disease.
Interventions
DEVICES.M.A.R.T. ® Stent
The Cordis S.M.A.R.T.® Nitinol Stent System is a self-expandable, crush recoverable stent with a diameter larger than that of the arterial lumen. The stent is indicated for use in a vessel with a diameter 1 to 2 mm smaller than the nominal stent diameter. This stent will open to the diameter of the artery and will continue to apply expanding force on the artery.
Sponsors
Cordis US Corp.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>/= 30 years * For women of child bearing potential, a pregnancy test within 7 days prior to index procedure (the test results must be negative to be eligible). * Symptomatic leg ischemia by Rutherford/Becker Classification (category 2, 3 or 4) with a resting or exercise ABI \</= 0.8. * A single superficial femoral artery lesion with \> 50% stenosis or total occlusion. * Stenotic lesion or occluded length within the same vessel (one long or multiple serial lesions) \>/= 4.0 cm to \</= 15.0 cm, by visual estimate. The stenosis must be treatable with no more than two stents, minimizing the stent overlap whose combined length \</= 170 mm. * Reference vessel diameter (RVD) \>/= 4.0 mm and \</= 6.0 mm by visual assessment. * All lesions are to be located at least three centimeters proximal to the superior edge of the patella. * Patent infrapopliteal and popliteal artery, i.e., single vessel runoff or better with at least one of three vessels patent (\< 50% stenosis) to the ankle or foot. * The guidewire is across the target lesion(s) and located intraluminally within the distal vessel. * Poor aortoiliac or common femoral inflow (i.e. angiographically defined \> 50% stenosis of the iliac or common femoral artery) that would be deemed inadequate to support a femoropopliteal bypass graft must be successfully treated prior to treatment of the target lesion. This can be done just prior to treatment of the target lesion. Successful treatment is defined as \<30% stenosis after either PTA or stenting of the inflow lesion. After treatment of the inflow lesion, if the peak to peak pressure gradient across the inflow lesion is \</= 20mmHg and the peak to peak pressure gradient across the SFA target lesion is \>/= 20mmHg, then the patient will be included in the study. * A patient with bilateral obstructive SFA disease is eligible for enrollment into the study. * Eligibility for standard surgical repair, if necessary. * A patient who requires a coronary intervention, should have it performed at least 7 days prior to the treatment of the target lesion. * Patient or authorized representative must provide written informed consent and written HIPAA authorization prior to initiation of study procedures. * Patient must be willing to comply with the specified follow-up evaluation schedule.
Exclusion criteria
* Thrombophlebitis, uremia, or deep venous thrombus, within past 30 days. * Receiving dialysis or immunosuppressant therapy. * Thrombolysis of the target vessel within 72 hours prior to the index procedure where complete resolution of the thrombus was not achieved. * Recent stroke within past 90 days. * Femoral, iliac or aortic aneurysm or aneurysm in the SFA or popliteal artery within past 5 years. * Required stent placement via a popliteal approach. * Required stent placement across or within 0.5 cm of the SFA / PFA bifurcation. * Procedures which are pre-determined to require stent-in-stent placement to obtain patency, such as severe calcification which is resistant to stenting, or for in-stent restenosis. * Significant vessel tortuosity or other parameters prohibiting access to the lesion or 90° tortuosity which would prevent delivery of the stent device. * Previously deployed stent within the SFA of the target limb. * Known allergies to the following: aspirin, clopidogrel bisulfate (Plavix®) or ticlopidine (Ticlid®), heparin, Nitinol (nickel titanium), contrast agent, that cannot be medically managed. * Presence of thrombus prior to crossing the lesion * Tissue loss due to ischemic disease (Rutherford/Becker category 5 or 6) * Serum creatinine level \>/= 2.5 mg/dl at time of screening visit * Known or suspected active infection at the time of the procedure * Bleeding diathesis * Presence of an aortic, iliac or femoral artificial graft * Life expectancy less than one year, or any other factors preventing clinical followup. * Use of cryoplasty, laser, or atherectomy devices on the target vessel at the time of index procedure * In-stent restenotic lesions at time of procedures. * Restenotic lesion that had previously been treated by atherectomy, laser, or cryoplasty within 90 days of the index procedure. * Patient is unwilling or unable to comply with procedures specified in the protocol or has difficulty or inability to return for follow-up visits as specified by the protocol. * Patient is known to be pregnant, incarcerated, mentally incompetent, and/or alcohol or drug abuser. * Patient is currently participating in any other investigational drug or medical device study that has not completed primary endpoint(s) evaluation or clinically interferes with the endpoints from this study or future participation in such studies prior to the completion of this study. * Patient has had major surgical or interventional procedures unrelated to this study within 30 days prior to this study or planned surgical or interventional procedures within 30 days of entry into this study. Interventional procedures performed to the ipsilateral iliac artery to provide access will be allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 12-month Primary Patency Rate | 12 months | Primary patency is defined as no significant reduction of flow detectable by Duplex ultrasound through the index lesion and no further clinically driven target vessel revascularization performed in the interim. Significant reduction of flow is binary restenosis defined as the diameter stenosis \>50% with a peak systolic velocity ratio \>2.0 as measured by Duplex ultrasound. |
| Primary Safety Endpoint | 30 days | Primary safety endpoint is defined as the rate of freedom from all causes of death, index limb amputation, and clinically driven target lesion revascularization (TLR) through 30 days. A clinically driven TLR is any intervention in the stented target lesion following documented recurrent symptomatic leg ischemia by Rutherford/Becker Classification (category 2, 3 or 4), with a resting or exercise ABI ≤ 0.8 and \>50% diameter in-lesion stenosis by angiography. Revascularization of a target lesion with an in-lesion diameter stenosis of \>70% by angiography, in the absence of the previously mentioned ischemic signs or symptoms, will also be considered clinically driven. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Index Limb Amputation at 30-day Follow up | 30 day | Index Limb Amputation is defined as surgical removal of all or part of the lower extremity from the toe up. |
| Clinically Driven Target Vessel Revascularization (TVR) at 30-day Post Procedure | 30 days | A clinically driven TVR is any intervention of the target vessel following documented recurrent symptomatic leg ischemia by Rutherford/Becker Classification (category 2, 3 or 4), with a resting or exercise Ankle-Brachial Index (ABI) ≤ 0.8 and \>50% diameter in-lesion stenosis by angiography. Revascularization of a target vessel with an in-lesion diameter stenosis of \>70% by angiography, in the absence of the previously mentioned ischemic signs or symptoms, will also be considered clinically driven. |
| Clinically Driven Target Vessel Revascularization (TVR) at 12-month Post Procedure | 12 months | A clinically driven TVR is any intervention of the target vessel following documented recurrent symptomatic leg ischemia by Rutherford/Becker Classification (category 2, 3 or 4), with a resting or exercise Ankle-Brachial Index (ABI) ≤ 0.8 and \>50% diameter in-lesion stenosis by angiography. Revascularization of a target vessel with an in-lesion diameter stenosis of \>70% by angiography, in the absence of the previously mentioned ischemic signs or symptoms, will also be considered clinically driven. |
| Stent Fracture at 12-month Follow Up | 12 months | Stent fracture was assessed by x-ray evaluation. |
| Death Rate at 30-day Post Procedure | 30 days | — |
| Index Limb Ischemia at 12-month Follow up | 12 months | Index Limb Ischemia is defined by Rutherford/Becker Classification categories 3 through 6. |
| Rutherford/Becker Classification at 30-day Follow Up | 30 days | The Rutherford/Becker Classification is a commonly used clinical staging system which allows clinicians to describe and discuss patients with peripheral artery disease. The classification has seven stages as follows: 1. Stage 0 - Asymptomatic, no hemodynamically significant occlusive disease 2. Stage 1 - Mild claudication 3. Stage 2 - Moderate claudication 4. Stage 3 - Severe claudication 5. Stage 4 - Ischemic rest pain 6. Stage 5 - Minor tissue loss, non-healing ulcer, focal gangrene with diffuse pedal ischemia 7. Stage 6 - Major tissue loss, extending above transmetatarsal level, functional foot no longer salvageable |
| Rutherford / Becker Classification Category at 12-month Follow Up | 12 months | — |
| Major Adverse Events at 12-month Post Procedure | 12 months | Major adverse events included death, index limb ischemia, index limb amputation, clinically driven TLR, and significant embolic events, which were defined as causing end-organ damage. |
| Index Limb Ischemia at 6-month Follow up | 6 months | Index Limb Ischemia is defined by Rutherford/Becker Classification categories 3 through 6. |
| Death at 12-month Post Procedure | 12 months | — |
Countries
United States
Participant flow
Recruitment details
A total of 250 patients were enrolled from August 14, 2008 to March 15, 2010 across 39 clinical sites in the U.S.
Pre-assignment details
This is a multi-center, non-randomized, single-arm, prospective trial. Patients were eligible for enrollment if they met all inclusion criteria and none of the exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| S.M.A.R.T.™ Nitinol Stent System The Cordis S.M.A.R.T.™ Nitinol Stent System is a self-expandable, crush recoverable stent with a diameter larger than that of the arterial lumen. The stent is indicated for use in a vessel with a diameter 1 to 2 mm smaller than the nominal stent diameter. This stent will open to the diameter of the artery and will continue to apply expanding force on the artery. | 250 |
| Total | 250 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 5 |
| Overall Study | Withdrawal by Subject | 10 |
Baseline characteristics
| Characteristic | S.M.A.R.T.™ Nitinol Stent System |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 157 Participants |
| Age, Categorical Between 18 and 65 years | 93 Participants |
| Age, Continuous | 67.71 years STANDARD_DEVIATION 10.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 240 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 participants |
| Race/Ethnicity, Customized Asian | 1 participants |
| Race/Ethnicity, Customized Black or African American | 31 participants |
| Race/Ethnicity, Customized Hispanic | 3 participants |
| Race/Ethnicity, Customized Middle Eastern | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants |
| Race/Ethnicity, Customized Other | 0 participants |
| Race/Ethnicity, Customized White or Caucasian | 214 participants |
| Region of Enrollment United States | 250 participants |
| Sex: Female, Male Female | 96 Participants |
| Sex: Female, Male Male | 154 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 93 / 250 |
| serious Total, serious adverse events | 5 / 250 |
Outcome results
Primary
12-month Primary Patency Rate
Primary patency is defined as no significant reduction of flow detectable by Duplex ultrasound through the index lesion and no further clinically driven target vessel revascularization performed in the interim. Significant reduction of flow is binary restenosis defined as the diameter stenosis \>50% with a peak systolic velocity ratio \>2.0 as measured by Duplex ultrasound.
Time frame: 12 months
Population: As a subset of the modified ITT, this analysis population consisted of the subjects who had ultrasound assessment at 12 months or had target vessel revascularization (TVR) performed by 12 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | 12-month Primary Patency Rate | Subjects Achieved Primary Patency | 143 participants |
| S.M.A.R.T.™ Nitinol Stent System | 12-month Primary Patency Rate | Subjects Didn't Achieve Primary Patency | 72 participants |
Comparison: The null hypothesis to be tested was Ho: P = 0.66 against Ha: P \> 0.66, where 0.66 was the Objective Performance Criteria (OPC). A sample size of 212 subjects was required to achieve 90% power to reject the 66% 12-months patency rate at a one-sided 2.5% significance level when the unknown true patency is at 76%.p-value: 0.43795% CI: [0.6, 0.725]Agresti-Coull method
Primary
Primary Safety Endpoint
Primary safety endpoint is defined as the rate of freedom from all causes of death, index limb amputation, and clinically driven target lesion revascularization (TLR) through 30 days. A clinically driven TLR is any intervention in the stented target lesion following documented recurrent symptomatic leg ischemia by Rutherford/Becker Classification (category 2, 3 or 4), with a resting or exercise ABI ≤ 0.8 and \>50% diameter in-lesion stenosis by angiography. Revascularization of a target lesion with an in-lesion diameter stenosis of \>70% by angiography, in the absence of the previously mentioned ischemic signs or symptoms, will also be considered clinically driven.
Time frame: 30 days
Population: Active subjects in the Modified ITT population at 30 days post procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | Primary Safety Endpoint | Subjects Achieved Primary Safety Endpoint | 248 participants |
| S.M.A.R.T.™ Nitinol Stent System | Primary Safety Endpoint | Subjects Didn't Achieve Primary Safety Endpoint | 0 participants |
Comparison: The null hypothesis to be tested was Ho: P = 0.88 against Ha: P \> 0.88, where 0.88 was the Objective Performance Criteria (OPC).p-value: <0.00195% CI: [98.2, 100]Agresti-Coull method
Secondary
Clinically Driven Target Vessel Revascularization (TVR) at 12-month Post Procedure
A clinically driven TVR is any intervention of the target vessel following documented recurrent symptomatic leg ischemia by Rutherford/Becker Classification (category 2, 3 or 4), with a resting or exercise Ankle-Brachial Index (ABI) ≤ 0.8 and \>50% diameter in-lesion stenosis by angiography. Revascularization of a target vessel with an in-lesion diameter stenosis of \>70% by angiography, in the absence of the previously mentioned ischemic signs or symptoms, will also be considered clinically driven.
Time frame: 12 months
Population: Active subjects in the Modified ITT population at 12-month post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | Clinically Driven Target Vessel Revascularization (TVR) at 12-month Post Procedure | 32 participants |
95% CI: [9.5, 18.6]
Secondary
Clinically Driven Target Vessel Revascularization (TVR) at 30-day Post Procedure
A clinically driven TVR is any intervention of the target vessel following documented recurrent symptomatic leg ischemia by Rutherford/Becker Classification (category 2, 3 or 4), with a resting or exercise Ankle-Brachial Index (ABI) ≤ 0.8 and \>50% diameter in-lesion stenosis by angiography. Revascularization of a target vessel with an in-lesion diameter stenosis of \>70% by angiography, in the absence of the previously mentioned ischemic signs or symptoms, will also be considered clinically driven.
Time frame: 30 days
Population: Active subjects in the Modified ITT population at 30-day post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | Clinically Driven Target Vessel Revascularization (TVR) at 30-day Post Procedure | 0 participants |
95% CI: [0, 1.5]
Secondary
Death at 12-month Post Procedure
Time frame: 12 months
Population: Active subjects in the Modified ITT population at 12-month post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | Death at 12-month Post Procedure | 5 participants |
95% CI: [0.7, 4.9]
Secondary
Death Rate at 30-day Post Procedure
Time frame: 30 days
Population: Active subjects in the Modified ITT population at 30-day post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | Death Rate at 30-day Post Procedure | 0 participants |
Secondary
Index Limb Amputation at 30-day Follow up
Index Limb Amputation is defined as surgical removal of all or part of the lower extremity from the toe up.
Time frame: 30 day
Population: Active subjects in the Modified ITT population at 30 days post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | Index Limb Amputation at 30-day Follow up | 0 participants |
95% CI: [0, 1.5]
Secondary
Index Limb Ischemia at 12-month Follow up
Index Limb Ischemia is defined by Rutherford/Becker Classification categories 3 through 6.
Time frame: 12 months
Population: Active subjects in the Modified ITT population at 12-month post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | Index Limb Ischemia at 12-month Follow up | 18 participants |
Secondary
Index Limb Ischemia at 6-month Follow up
Index Limb Ischemia is defined by Rutherford/Becker Classification categories 3 through 6.
Time frame: 6 months
Population: Active subjects in the Modified ITT population at 6-month post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | Index Limb Ischemia at 6-month Follow up | 12 participants |
Secondary
Major Adverse Events at 12-month Post Procedure
Major adverse events included death, index limb ischemia, index limb amputation, clinically driven TLR, and significant embolic events, which were defined as causing end-organ damage.
Time frame: 12 months
Population: Active subjects in the Modified ITT population at 12-month post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | Major Adverse Events at 12-month Post Procedure | 34 participants |
95% CI: [10.2, 19.5]
Secondary
Rutherford/Becker Classification at 30-day Follow Up
The Rutherford/Becker Classification is a commonly used clinical staging system which allows clinicians to describe and discuss patients with peripheral artery disease. The classification has seven stages as follows: 1. Stage 0 - Asymptomatic, no hemodynamically significant occlusive disease 2. Stage 1 - Mild claudication 3. Stage 2 - Moderate claudication 4. Stage 3 - Severe claudication 5. Stage 4 - Ischemic rest pain 6. Stage 5 - Minor tissue loss, non-healing ulcer, focal gangrene with diffuse pedal ischemia 7. Stage 6 - Major tissue loss, extending above transmetatarsal level, functional foot no longer salvageable
Time frame: 30 days
Population: Active subjects in the Modified ITT population at 30-day post procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | Rutherford/Becker Classification at 30-day Follow Up | Rutherford/Becker Classification - 2 | 38 participants |
| S.M.A.R.T.™ Nitinol Stent System | Rutherford/Becker Classification at 30-day Follow Up | Rutherford/Becker Classification - 6 | 0 participants |
| S.M.A.R.T.™ Nitinol Stent System | Rutherford/Becker Classification at 30-day Follow Up | Rutherford/Becker Classification - 0 | 157 participants |
| S.M.A.R.T.™ Nitinol Stent System | Rutherford/Becker Classification at 30-day Follow Up | Rutherford/Becker Classification - 1 | 39 participants |
| S.M.A.R.T.™ Nitinol Stent System | Rutherford/Becker Classification at 30-day Follow Up | Rutherford/Becker Classification - 3 | 8 participants |
| S.M.A.R.T.™ Nitinol Stent System | Rutherford/Becker Classification at 30-day Follow Up | Rutherford/Becker Classification - 4 | 1 participants |
| S.M.A.R.T.™ Nitinol Stent System | Rutherford/Becker Classification at 30-day Follow Up | Rutherford/Becker Classification - 5 | 0 participants |
Secondary
Rutherford / Becker Classification Category at 12-month Follow Up
Time frame: 12 months
Population: Active subjects in the Modified ITT population at 12-month post procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | Rutherford / Becker Classification Category at 12-month Follow Up | Rutherford/Becker Classification - 0 | 125 participants |
| S.M.A.R.T.™ Nitinol Stent System | Rutherford / Becker Classification Category at 12-month Follow Up | Rutherford/Becker Classification - 1 | 39 participants |
| S.M.A.R.T.™ Nitinol Stent System | Rutherford / Becker Classification Category at 12-month Follow Up | Rutherford/Becker Classification - 2 | 32 participants |
| S.M.A.R.T.™ Nitinol Stent System | Rutherford / Becker Classification Category at 12-month Follow Up | Rutherford/Becker Classification - 3 | 16 participants |
| S.M.A.R.T.™ Nitinol Stent System | Rutherford / Becker Classification Category at 12-month Follow Up | Rutherford/Becker Classification - 4 | 1 participants |
| S.M.A.R.T.™ Nitinol Stent System | Rutherford / Becker Classification Category at 12-month Follow Up | Rutherford/Becker Classification - 5 | 1 participants |
| S.M.A.R.T.™ Nitinol Stent System | Rutherford / Becker Classification Category at 12-month Follow Up | Rutherford/Becker Classification - 6 | 0 participants |
Secondary
Stent Fracture at 12-month Follow Up
Stent fracture was assessed by x-ray evaluation.
Time frame: 12 months
Population: Active subjects in the Modified ITT population at 12-month post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| S.M.A.R.T.™ Nitinol Stent System | Stent Fracture at 12-month Follow Up | 3 participants |
95% CI: [0.3, 4.4]