Femoral Artery Occlusion, Femoral Artery Stenosis, Popliteal Artery Occlusion, Popliteal Artery Stenosis
Conditions
Keywords
Drug-Coated Angioplasty Balloon, Drug Coated Angioplasty Balloon, Peripheral Artery Disease, Experimental, Percutaneous Transluminal Angioplasty (PTA)
Brief summary
The purpose of the study is to demonstrate the safety and efficacy of the IN.PACT Admiral drug-coated balloon (DCB) in comparison to any standard balloon for treatment of peripheral arterial disease (PAD) in the superficial femoral artery and proximal popliteal artery.
Detailed description
The IN.PACT SFA Trial enrolled in 2 phases: IN.PACT SFA I and IN.PACT SFA II. The 150-patient IN.PACT SFA I phase is intended to support the second phase IN.PACT SFA II IDE trial with congruent design and protocol. Aggregate data from the two phases is intended to provide statistical power for the 12-month primary safety and effectiveness endpoints.
Interventions
Subjects will be randomized 2:1 to the IN.PACT Admiral Drug-Coated Balloon (DCB) Arm or to the standard angioplasty balloon Arm
Subjects will be randomized 2:1 to the IN.PACT Admiral Drug-Coated Balloon (DCB) Arm or to the standard angioplasty balloon Arm
Sponsors
Medtronic Endovascular
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Age: \> or equal to 18 years and \< or equal to 85 years * Documented ischemia with Rutherford classification 2, 3, or 4 * Target lesion in the SFA and/or PPA * Angiographic evidence that target lesion consists of a single de novo or non-stented restenotic lesion or is a combination lesion that meets the following criteria: 1. 70 - 99% occlusion by visual estimate with lesion length \> or equal to 4 cm and \< or equal to 18 cm 2. 100% occlusion by visual estimate with lesion length \< or equal to 10 cm 3. Combination lesions must have a total lesion length of \> or equal to 4 cm and \< or equal to 18 cm with an occluded segment that is \< or equal to 10 cm (by visual estimate) * Target vessel diameter \> or equal to 4 mm and \< or equal to 7 mm * Angiographic evidence of adequate distal run-off to the ankle * Able to walk without assistive devices
Exclusion criteria
* Stroke or heart attack within 3 months prior to enrollment * Enrolled in another investigational drug, device or biologic study * Any surgical procedure or intervention performed within 30 days prior to or post index procedure * SFA or PPA disease in the opposite leg that requires treatment at the index procedure * Failure to successfully cross the target lesion * Angiographic evidence of severe calcification * Target lesion requires treatment with alternative therapies such as stenting, laser, atherectomy, cryoplasty, brachytherapy, re-entry devices) * Known allergies or sensitivity to heparin, aspirin, other anticoagulant/antiplatelet therapies, paclitaxel or contrast media that cannot be adequately pre-treated prior to index procedure * Chronic kidney disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Patency | 12 month | Primary patency is defined as freedom from clinically-driven target lesion revascularisation (CD-TLR) or restenosis as determined by duplex ultrasound (DUS) Peak Systolic Velocity Ratio (PSVR) ≤2.4. |
| Primary Safety Composite | 12 month | Primary safety composite is defined as freedom from death through 30 days or target limb major amputation or clinically-driven target vessel revascularization (CD-TVR) within 12 months post index procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Primary Sustained Clinical Improvement | 12 month | Freedom from target limb amputation, target vessel revascularization (TVR), and increase in Rutherford class. |
| Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >2.4) | 12 month | — |
| Major Adverse Event (MAE) Composite | 12 month | Major Adverse Event (MAE) composite is defined as all cause death, clinically-driven target vessel revascularization, major target limb amputation, thrombosis at the target lesion site. |
| All-cause Death | 12 month | — |
| Target Vessel Revascularization (TVR) | 12 month | — |
| Target Lesion Revascularization (TLR) | 12 month | — |
| Time to First Clinically Driven Target Lesion Revascularization (CD-TLR) | 12 month | Clinically-driven target lesion revascularization (CD-TLR) is defined as any re-intervention within the target lesion due to symptoms or drop of ankle brachial index (ABI) of ≥20% or \>0.15 when compared to post procedure baseline. |
| Major Target Limb Amputation | 12 month | — |
| Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >3.4) | 12 month | — |
| Quality of Life Assessment by EuroQol Group 5-Dimension Self-Report Questionnaire (EQ5D) | 12 month | Quality of life assessment by EQ5D at 1 year compared to baseline. EQ5D is a standardised measure of health status and economic appraisal. The EQ5D consists of the EQ5D descriptive system which comprises the following variables for the 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: (1) no problems, (2) some problems, (3) extreme problems. A complex algorithm that took individual dimensions and generated an overall score was used. EQ5D health state is used in the algorithm to calculate an overall score where - 0.109 = 'worst possible outcome' and 1.000 = 'best possible outcome'. |
| Change in Walking Distance as Assessed by Six Minute Walk Test (6MWT) | From baseline to 12 month | Change from baseline in walking distance by Six Minute Walk Test (6MWT) at 12 month. |
| Walking Capacity Assessment by Walking Impairment Questionnaire (WIQ) | 12 month | Walking capacity assessment by WIQ at 1 year compared to baseline. WIQ is a quality of life questionnaire that was specifically designed to assess the degree of impairment experienced by patients with claudication. Clinical outcomes were assessed by patients responses to question 1A. Question 1A is specific for calf or buttocks claudication and is used to create a summary score for analysis. Question 1A is expressed on a scale of 0% (unable to perform because of severe claudication) to 100% (no impairment). |
| Device Success | Day 1 | Device success is defined as successful delivery, balloon inflation and deflation and retrieval of the intact study device without burst below rated burst pressure (RBP). |
| Procedural Success | Day 1 | Procedural success is defined as residual stenosis of ≤50% (non-stented subjects) or ≤30% (stented subjects) by core lab assessment. |
| Clinical Success | Day 1 | Clinical success is defined as procedural success without procedural complications (death, major target limb amputation, thrombosis of the target lesion, or Target vessel revascularization (TVR)) prior to discharge. |
| Days of Hospitalization Due to the Index Lesion | 12 month | Days of hospitalization from procedure through 12 month. |
| Thrombosis at the Target Lesion | 12 month | — |
| Secondary Sustained Clinical Improvement | 12 month | Freedom from target amputation and increase in Rutherford class. |
Countries
United States
Participant flow
Pre-assignment details
The IN.PACT SFA Trial was designed as a two-phase randomized trial. IN.PACT SFA I, the first phase, was conducted in Europe with 150 subjects enrolled. IN.PACT SFA II, the second phase, was conducted in the US with 181 subjects enrolled. The randomized data from both phases are pooled and comprise the pivotal trial data.
Participants by arm
| Arm | Count |
|---|---|
| Drug-Coated Balloon (DCB) Paclitaxel drug-coated angioplasty balloon
IN.PACT Admiral Drug-Coated Balloon: Subjects will be randomized 2:1 to the IN.PACT Admiral Drug-Coated Balloon Arm or to the standard angioplasty balloon Arm | 220 |
| Standard PTA Standard angioplasty balloon without Paclitaxel drug-coating
Standard angioplasty balloon: Subjects will be randomized 2:1 to the IN.PACT Admiral Drug-Coated Balloon Arm or to the standard angioplasty balloon Arm | 111 |
| Total | 331 |
Baseline characteristics
| Characteristic | Drug-Coated Balloon (DCB) | Standard PTA | Total |
|---|---|---|---|
| Age, Continuous | 67.5 Years STANDARD_DEVIATION 9.5 | 68.0 Years STANDARD_DEVIATION 9.2 | 67.6 Years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 77 Participants | 36 Participants | 113 Participants |
| Sex: Female, Male Male | 143 Participants | 75 Participants | 218 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 104 / 220 | 62 / 111 |
| serious Total, serious adverse events | 102 / 220 | 62 / 111 |
Outcome results
Primary
Primary Patency
Primary patency is defined as freedom from clinically-driven target lesion revascularisation (CD-TLR) or restenosis as determined by duplex ultrasound (DUS) Peak Systolic Velocity Ratio (PSVR) ≤2.4.
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Primary Patency | 82.2 Percentage of participants |
| Standard PTA | Primary Patency | 52.4 Percentage of participants |
p-value: <0.001z-test
Primary
Primary Safety Composite
Primary safety composite is defined as freedom from death through 30 days or target limb major amputation or clinically-driven target vessel revascularization (CD-TVR) within 12 months post index procedure.
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Primary Safety Composite | 95.7 Percentage of particpants |
| Standard PTA | Primary Safety Composite | 76.6 Percentage of particpants |
p-value: <0.001Chi-squared
Secondary
All-cause Death
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | All-cause Death | 1.9 Percentage of participants |
| Standard PTA | All-cause Death | 0 Percentage of participants |
p-value: 0.926Chi-squared
Secondary
Change in Walking Distance as Assessed by Six Minute Walk Test (6MWT)
Change from baseline in walking distance by Six Minute Walk Test (6MWT) at 12 month.
Time frame: From baseline to 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe. Data not collected in IN.PACT SFA I phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drug-Coated Balloon (DCB) | Change in Walking Distance as Assessed by Six Minute Walk Test (6MWT) | 38.7 Meters | Standard Deviation 92.1 |
| Standard PTA | Change in Walking Distance as Assessed by Six Minute Walk Test (6MWT) | 59.1 Meters | Standard Deviation 102.3 |
p-value: 0.878t-test, 1 sided
Secondary
Clinical Success
Clinical success is defined as procedural success without procedural complications (death, major target limb amputation, thrombosis of the target lesion, or Target vessel revascularization (TVR)) prior to discharge.
Time frame: Day 1
Population: Intention-to-Treat (n=331)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Clinical Success | 99.1 Percentage of participants |
| Standard PTA | Clinical Success | 97.3 Percentage of participants |
p-value: 0.103Chi-squared
Secondary
Days of Hospitalization Due to the Index Lesion
Days of hospitalization from procedure through 12 month.
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drug-Coated Balloon (DCB) | Days of Hospitalization Due to the Index Lesion | 1.3 Days | Standard Deviation 1.9 |
| Standard PTA | Days of Hospitalization Due to the Index Lesion | 1.7 Days | Standard Deviation 2 |
p-value: 0.049t-test, 1 sided
Secondary
Device Success
Device success is defined as successful delivery, balloon inflation and deflation and retrieval of the intact study device without burst below rated burst pressure (RBP).
Time frame: Day 1
Population: Total number of devices used in the ITT population (n=331).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Device Success | 99.0 Percentage of devices |
| Standard PTA | Device Success | 98.5 Percentage of devices |
p-value: 0.302Chi-squared
Secondary
Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >2.4)
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >2.4) | 16.5 Percentage of participants |
| Standard PTA | Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >2.4) | 33.7 Percentage of participants |
p-value: 0.001Chi-squared
Secondary
Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >3.4)
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >3.4) | 7.3 Percentage of participants |
| Standard PTA | Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >3.4) | 21.4 Percentage of participants |
p-value: <0.001Chi-squared
Secondary
Major Adverse Event (MAE) Composite
Major Adverse Event (MAE) composite is defined as all cause death, clinically-driven target vessel revascularization, major target limb amputation, thrombosis at the target lesion site.
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Major Adverse Event (MAE) Composite | 6.3 Percentage of participants |
| Standard PTA | Major Adverse Event (MAE) Composite | 24.3 Percentage of participants |
p-value: <0.001Chi-squared
Secondary
Major Target Limb Amputation
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Major Target Limb Amputation | 0 Percentage of participants |
| Standard PTA | Major Target Limb Amputation | 0 Percentage of participants |
p-value: >0.999Chi-squared
Secondary
Primary Sustained Clinical Improvement
Freedom from target limb amputation, target vessel revascularization (TVR), and increase in Rutherford class.
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Primary Sustained Clinical Improvement | 85.2 Percentage of participants |
| Standard PTA | Primary Sustained Clinical Improvement | 68.9 Percentage of participants |
p-value: <0.001Chi-squared
Secondary
Procedural Success
Procedural success is defined as residual stenosis of ≤50% (non-stented subjects) or ≤30% (stented subjects) by core lab assessment.
Time frame: Day 1
Population: Intention-to-Treat (n=331)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Procedural Success | 99.5 Percentage of participants |
| Standard PTA | Procedural Success | 98.2 Percentage of participants |
p-value: 0.111Chi-squared
Secondary
Quality of Life Assessment by EuroQol Group 5-Dimension Self-Report Questionnaire (EQ5D)
Quality of life assessment by EQ5D at 1 year compared to baseline. EQ5D is a standardised measure of health status and economic appraisal. The EQ5D consists of the EQ5D descriptive system which comprises the following variables for the 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: (1) no problems, (2) some problems, (3) extreme problems. A complex algorithm that took individual dimensions and generated an overall score was used. EQ5D health state is used in the algorithm to calculate an overall score where - 0.109 = 'worst possible outcome' and 1.000 = 'best possible outcome'.
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drug-Coated Balloon (DCB) | Quality of Life Assessment by EuroQol Group 5-Dimension Self-Report Questionnaire (EQ5D) | 0.1059 Units on a scale | Standard Deviation 0.2089 |
| Standard PTA | Quality of Life Assessment by EuroQol Group 5-Dimension Self-Report Questionnaire (EQ5D) | 0.0730 Units on a scale | Standard Deviation 0.1951 |
p-value: 0.095t-test, 1 sided
Secondary
Secondary Sustained Clinical Improvement
Freedom from target amputation and increase in Rutherford class.
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Secondary Sustained Clinical Improvement | 89.3 Percentage of particpants |
| Standard PTA | Secondary Sustained Clinical Improvement | 84.6 Percentage of particpants |
p-value: 0.121Chi-squared
Secondary
Target Lesion Revascularization (TLR)
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Target Lesion Revascularization (TLR) | 2.9 Percentage of participants |
| Standard PTA | Target Lesion Revascularization (TLR) | 20.6 Percentage of participants |
p-value: <0.001Chi-squared
Secondary
Target Vessel Revascularization (TVR)
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Target Vessel Revascularization (TVR) | 4.8 Percentage of participants |
| Standard PTA | Target Vessel Revascularization (TVR) | 23.4 Percentage of participants |
p-value: <0.001Chi-squared
Secondary
Thrombosis at the Target Lesion
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Drug-Coated Balloon (DCB) | Thrombosis at the Target Lesion | 1.4 Percentage of participants |
| Standard PTA | Thrombosis at the Target Lesion | 3.7 Percentage of participants |
p-value: 0.096Chi-squared
Secondary
Time to First Clinically Driven Target Lesion Revascularization (CD-TLR)
Clinically-driven target lesion revascularization (CD-TLR) is defined as any re-intervention within the target lesion due to symptoms or drop of ankle brachial index (ABI) of ≥20% or \>0.15 when compared to post procedure baseline.
Time frame: 12 month
Population: Includes all subjects who experienced a CD-TLR.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drug-Coated Balloon (DCB) | Time to First Clinically Driven Target Lesion Revascularization (CD-TLR) | 144.6 Days | Standard Deviation 159.6 |
| Standard PTA | Time to First Clinically Driven Target Lesion Revascularization (CD-TLR) | 201.9 Days | Standard Deviation 90.9 |
p-value: 0.859t-test, 1 sided
Secondary
Walking Capacity Assessment by Walking Impairment Questionnaire (WIQ)
Walking capacity assessment by WIQ at 1 year compared to baseline. WIQ is a quality of life questionnaire that was specifically designed to assess the degree of impairment experienced by patients with claudication. Clinical outcomes were assessed by patients responses to question 1A. Question 1A is specific for calf or buttocks claudication and is used to create a summary score for analysis. Question 1A is expressed on a scale of 0% (unable to perform because of severe claudication) to 100% (no impairment).
Time frame: 12 month
Population: Intention-to-Treat population (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drug-Coated Balloon (DCB) | Walking Capacity Assessment by Walking Impairment Questionnaire (WIQ) | 72.7 Units on a scale | Standard Deviation 31.4 |
| Standard PTA | Walking Capacity Assessment by Walking Impairment Questionnaire (WIQ) | 73.6 Units on a scale | Standard Deviation 29.5 |
p-value: 0.59t-test, 1 sided