Peripheral Arterial Disease (PAD)
Conditions
Brief summary
The objective of this Study is to evaluate the safety and efficacy of the IN.PACT Admiral® drug coated PTA balloon, utilized for the dilatation of the narrowed sections of the artery, as compared to other standard (non drug coated) PTA balloons. The IN.PACT Admiral, besides the mechanical dilatation effect typical of all PTA balloons, releases a drug (paclitaxel) from the balloon surface into the vessel walls. This drug absorption is intended to limit the chances and the entity of artery re-narrowing over time.
Detailed description
The efficacy of the IN.PACT Admiral balloon will be evaluated by assessing the primary patency rate of the treated arteries in the thighs of all patients included in the Study. Primary patency is a measure of the durability up to 1 year of the free lumen in the artery as restored during the procedure and is based on: * the need for re-dilatation of the previously treated vessel segment * an ultrasound examination The safety of the IN.PACT Admiral will be assessed by evaluating the incidence of deaths, amputations and re-dilatation of the pre-treated arteries in all patients included in the Study. 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
balloon dilatation and provisional stenting with IN.PACT DCB
balloon dilatation and provisional stenting with standard non-coated PTA balloon
Sponsors
Medtronic Endovascular
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: * Age ≥18 years and ≤85 years * Patient or patient's legal representative is informed of the nature of the study, agrees to participate and has signed an EC approved consent form Angiographic Inclusion Criteria: \- Target vessel is the superficial femoral artery and/or proximal popliteal artery (above the knee) General
Exclusion criteria
* Patient unwilling or unlikely to comply with follow-up schedule * Stroke or STEMI within 3 months prior enrolment Angiographic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Patency | 12 Month | Primary patency is defined as freedom from clinically-driven target lesion revascularization (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 |
|---|---|---|
| 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 | — |
| Thrombosis at the Target Lesion | 12 month | — |
| Primary Sustained Clinical Improvement | 12 month | Freedom from target limb amputation, target vessel revascularization (TVR), and increase in Rutherford class. Rutherford classification is a clinical staging system that is used to describe peripheral arterial disease. |
| Secondary Sustained Clinical Improvement | 12 month | Freedom from target limb amputation and increase in Rutherford class. |
| Major Adverse Events (MAE) Composite | 12 month | Major Adverse Events (MAE) composite defined as all-cause death, clinically-driven target vessel revascularization (CD-TVR), major target limb amputation, thrombosis at the target lesion site |
| Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio >3.4). | 12 month | — |
| Change From Baseline in Quality of Life Assessment by EuroQol Group 5-Dimension Self Report Questionnaire (EQ5D) at Month 12 | Baseline to 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 From Baseline in Walking Capacity Assessment by Walking Impairment Questionnaire (WIQ) at 12 Months | 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 obtainment of ≤30% residual stenosis by visual estimate (with or without stenting) |
| Clinical Success | Day 1 | Clinical success is defined as procedural success without procedural complications (death, stroke, 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. |
| Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >2.4). | 12 month | Duplex ultrasound measurement that measures the peak systolic velocity of blood (cm/sec) within a lesion divided by the peak velocity of blood (cm/sec) proximal to the lesion. |
| All-cause Death | 12 month | — |
Countries
Germany
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 data from both phases of the IN.PACT SFA Trial have been 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 | 67.5 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 revascularization (TLR) or restenosis as determined by duplex ultrasound (DUS) Peak Systolic Velocity Ratio (PSVR) ≤ 2.4.
Time frame: 12 Month
Population: Intention-to-Treat (ITT) (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 (ITT) (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 Participants |
| Standard PTA | Primary Safety Composite | 76.6 Percentage of Participants |
p-value: <0.001Chi-squared
Secondary
All-cause Death
Time frame: 12 month
Population: Intention-to-Treat (ITT) (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 | 0.0 percentage of participants |
p-value: 0.926Chi-squared
Secondary
Change From Baseline in Quality of Life Assessment by EuroQol Group 5-Dimension Self Report Questionnaire (EQ5D) at Month 12
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: Baseline to 12 month
Population: Intention-to-Treat (ITT) (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drug-Coated Balloon (DCB) | Change From Baseline in Quality of Life Assessment by EuroQol Group 5-Dimension Self Report Questionnaire (EQ5D) at Month 12 | 0.1059 Units on a scale | Standard Deviation 0.2089 |
| Standard PTA | Change From Baseline in Quality of Life Assessment by EuroQol Group 5-Dimension Self Report Questionnaire (EQ5D) at Month 12 | 0.0730 Units on a scale | Standard Deviation 0.1951 |
p-value: 0.095Chi-squared
Secondary
Change From Baseline in Walking Capacity Assessment by Walking Impairment Questionnaire (WIQ) at 12 Months
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 (ITT) (n=331) that excludes subjects who did not have evaluable data at the reporting timeframe.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Drug-Coated Balloon (DCB) | Change From Baseline in Walking Capacity Assessment by Walking Impairment Questionnaire (WIQ) at 12 Months | 72.7 Units on a scale | Standard Deviation 31.4 |
| Standard PTA | Change From Baseline in Walking Capacity Assessment by Walking Impairment Questionnaire (WIQ) at 12 Months | 73.6 Units on a scale | Standard Deviation 29.5 |
p-value: 0.59Chi-squared
Secondary
Clinical Success
Clinical success is defined as procedural success without procedural complications (death, stroke, 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 (ITT) (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 (ITT) (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: 0.049Chi-squared
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 >3.4).
Time frame: 12 month
Population: Intention-to-Treat (ITT) (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 >3.4). | 7.3 Percentage of particpants |
| Standard PTA | Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio >3.4). | 21.4 Percentage of particpants |
p-value: <0.001Chi-squared
Secondary
Duplex-defined Binary Restenosis (Peak Systolic Velocity Ratio (PSVR) >2.4).
Duplex ultrasound measurement that measures the peak systolic velocity of blood (cm/sec) within a lesion divided by the peak velocity of blood (cm/sec) proximal to the lesion.
Time frame: 12 month
Population: Intention-to-Treat (ITT) (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
Major Adverse Events (MAE) Composite
Major Adverse Events (MAE) composite defined as all-cause death, clinically-driven target vessel revascularization (CD-TVR), major target limb amputation, thrombosis at the target lesion site
Time frame: 12 month
Population: Intention-to-Treat (ITT) (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 Events (MAE) Composite | 6.3 Percentage of participants |
| Standard PTA | Major Adverse Events (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 (ITT) (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 amputations |
| Standard PTA | Major Target Limb Amputation | 0 percentage of amputations |
p-value: >0.999Chi-squared
Secondary
Primary Sustained Clinical Improvement
Freedom from target limb amputation, target vessel revascularization (TVR), and increase in Rutherford class. Rutherford classification is a clinical staging system that is used to describe peripheral arterial disease.
Time frame: 12 month
Population: Intention-to-Treat (ITT) (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 particpants |
| Standard PTA | Primary Sustained Clinical Improvement | 68.9 percentage of particpants |
p-value: <0.001Chi-squared
Secondary
Procedural Success
Procedural success is defined as obtainment of ≤30% residual stenosis by visual estimate (with or without stenting)
Time frame: Day 1
Population: Intention-to-Treat (ITT) (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
Secondary Sustained Clinical Improvement
Freedom from target limb amputation and increase in Rutherford class.
Time frame: 12 month
Population: Intention-to-Treat (ITT) (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 participants |
| Standard PTA | Secondary Sustained Clinical Improvement | 84.6 percentage of participants |
p-value: 0.121Chi-squared
Secondary
Target Lesion Revascularization (TLR)
Time frame: 12 month
Population: Intention-to-Treat (ITT) (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 (ITT) (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 (ITT) (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: 0.859Chi-squared