PAD, Vascular Calcification
Conditions
Keywords
Drug-coated Balloons, Calcified Lesions, Orbital Atherectomy, Below the Knee, Paclitaxel, Lutonix 014 Drug-coated Balloon
Brief summary
The purpose of this study is to prospectively evaluate acute and long term clinical results of orbital atherectomy (OA) with adjunctive drug coated balloon (DCB) angioplasty versus DCB angioplasty alone for treatment of Peripheral Artery Disease (PAD) in below the knee (BTK) lesions.
Interventions
DEVICEPeripheral Orbital Atherectomy System
Orbital Atherectomy
DEVICE014 Drug Coated Balloon
Drug Coated Balloon
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject's age ≥ 18 years * Rutherford Clinical Category 3 - 5 * Lesions \[except in-stent restenosis (ISR)\] of the distal popliteal (POP segment below the anatomical knee joint), anterior tibial, posterior tibial, tibial peroneal trunk, and peroneal arteries with ≥ 70 % diameter stenosis (DS) by angiography * Presence of clearly visible calcification in two views (both sides of vessel at the same location) evaluated angiographically- \[Computerized tomography (CT) angio images may substitute to confirm distribution of calcium, if available as standard of care\] * Length of calcium ≥ 25 % of total lesion length or ≥ 2 cm total length * Target lesion length up to 20 cm
Exclusion criteria
* Subject or subject's legal representative is not willing to sign an Ethics Committee approved informed consent form or comply with the study protocol requirements * Contraindicated by either device, per Instructions For Use * Presence of inflow lesion (≥ 50 % DS) or inflow not successfully treated (≥ 50% DS and/or unresolved significant angiographic complication) * Compromised outflow distal to the target lesion (≥ 70 % DS) or presence of lesion(s) or occlusion(s) located from 5 cm above the ankle to below the ankle joint space * Subject has more than 2 target vessels requiring treatment * The guide wire cannot be passed across the target lesion(s) and/or guide wire position distal to target lesion(s) outside vessel lumen * Presence of significant (≥ 70 % DS) lesion(s) or occlusion(s) not meeting the study criteria which were not successfully treated during the index procedure (≥ 50 % DS and/or significant angiographic complication) * Subject has planned amputation (including minor) of the index limb or previous major amputation of the contralateral limb * Creatinine \> 2.5 mg/dL, unless on dialysis * Subject has any significant medical condition which, in the Investigator's opinion, may interfere with the subject's optimal participation in the study * Subject is participating in an investigational drug or device study that has the potential to clinically interfere with the study outcome measures * Subject is pregnant or planning to become pregnant within the study period * Subject has an unresolved severe systemic infection * Subject has an anticipated life span of less than one year * Subjects with known hypersensitivity to paclitaxel or paclitaxel related compounds * Subjects who cannot receive recommended anti-platelet and/or anticoagulant therapy * Pre-dilatation of the target lesion prior to randomization and OA treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Device Success | During the procedure | Device success was defined as the ability to achieve successful delivery and deployment of the drug-coated balloon (DCB) to the target lesion as described per Instructions for Use (IFU) within 3 minutes of insertion without removal and use of an additional device. The percentage of success was based on the number of DCB devices used. |
| Patency of the Target Lesion at 6 Months and 12 Months Post-Procedure | 6 months and 12 months post-procedure | Patency of the target lesion as reported by the Duplex Ultrasound (DUS) Core Laboratory. Vessel patency at 6 months and 12 months by Duplex Ultrasound (DUS), where patency is defined as \<50% restenosis within the treated lesion area. Patency was assessed by the DUS Core Laboratory. |
| Freedom From Clinically-Driven Target Lesion Revascularization (CD-TLR) at 6 Months and 12 Months Post-Procedure | 6 months and 12 months post-procedure | A Kaplan-Meier analysis was performed to determine the percent probability that a study participant was free from CD-TLR through 6 months and 12 months. |
| Freedom From Unplanned, Unavoidable Major Amputation of the Index Limb at 6 Months and 12 Months Post-Procedure | 6 months and 12 months post-procedure | A Kaplan-Meier analysis was performed to determine the percent probability that the study participant was free from an unplanned, unavoidable major amputation of the index limb through 6 months and 12 months. |
| Freedom From Major Adverse Events (MAEs) at 6 Months and 12 Months Post-Procedure | 6 months and 12 months post-procedure | A Kaplan-Meier analysis was performed to determine the percent probability that the study participant was free from a major adverse event (MAE) through 6 months and 12 months. Major adverse events were defined as: clinically-driven target lesion revascularization (CD-TLR); unplanned, unavoidable major amputation of the index limb; and death within 30 days of the index procedure. |
| Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline, 6 months and 12 months post-procedure | Rutherford Classification (RC) is a commonly used clinical grading system for describing peripheral arterial disease (PAD) on a scale of 0 to 6. RC 6 is the most severe form of PAD. There are seven Rutherford categories used to grade the severity of peripheral artery disease; 0: asymptomatic, 1: mild claudication, 2: moderate claudication, 3: severe claudication, 4: ischemic rest pain, 5: minor tissue loss, 6: major tissue loss. The change in Rutherford category is presented as the distribution at baseline compared to that at 6- and 12-months post-procedure. |
Countries
Austria, Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OA With Adjunctive DCB Angioplasty Lesion preparation with Peripheral Orbital Atherectomy System followed by drug-coated balloon angioplasty
Peripheral Orbital Atherectomy System: Orbital Atherectomy
014 Drug Coated Balloon: Drug Coated Balloon | 32 |
| DCB Angioplasty 014 Drug Coated Balloon angioplasty
014 Drug Coated Balloon: Drug Coated Balloon | 34 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 4 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | OA With Adjunctive DCB Angioplasty | DCB Angioplasty | Total |
|---|---|---|---|
| Age, Continuous | 73.4 years STANDARD_DEVIATION 8.5 | 76.5 years STANDARD_DEVIATION 7.1 | 75.0 years STANDARD_DEVIATION 7.9 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Rutherford Clinical Category Ischemic Rest Pain (4) | 2 Participants | 4 Participants | 6 Participants |
| Rutherford Clinical Category Minor Tissue Loss (5) | 20 Participants | 22 Participants | 42 Participants |
| Rutherford Clinical Category Severe Claudication (3) | 10 Participants | 8 Participants | 18 Participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 26 Participants | 25 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 32 | 4 / 34 |
| other Total, other adverse events | 4 / 32 | 2 / 34 |
| serious Total, serious adverse events | 29 / 32 | 22 / 34 |
Outcome results
Primary
Change in Rutherford Category at 6 Months and 12 Months Post-Procedure
Rutherford Classification (RC) is a commonly used clinical grading system for describing peripheral arterial disease (PAD) on a scale of 0 to 6. RC 6 is the most severe form of PAD. There are seven Rutherford categories used to grade the severity of peripheral artery disease; 0: asymptomatic, 1: mild claudication, 2: moderate claudication, 3: severe claudication, 4: ischemic rest pain, 5: minor tissue loss, 6: major tissue loss. The change in Rutherford category is presented as the distribution at baseline compared to that at 6- and 12-months post-procedure.
Time frame: Baseline, 6 months and 12 months post-procedure
Population: The number of participants analyzed at 6 and 12 months differs from the overall number due to missing data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 3 | 1 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 5 | 20 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 4 | 0 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 1 | 0 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 5 | 8 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 6 | 0 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 6 | 0 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 3 | 10 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 0 | 10 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 0 | 6 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 0 | 0 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 2 | 2 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 1 | 5 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 3 | 4 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 4 | 2 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 4 | 0 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 2 | 2 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 5 | 5 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 2 | 0 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 6 | 0 Participants |
| OA With Adjunctive DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 1 | 3 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 6 | 0 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 0 | 0 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 1 | 0 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 2 | 0 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 3 | 8 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 4 | 4 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 5 | 22 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | Baseline | Rutherford Category 6 | 0 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 0 | 7 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 1 | 1 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 2 | 0 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 3 | 1 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 4 | 0 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 5 | 8 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 6 months | Rutherford Category 6 | 0 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 0 | 8 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 1 | 3 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 2 | 1 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 3 | 1 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 4 | 0 Participants |
| DCB Angioplasty | Change in Rutherford Category at 6 Months and 12 Months Post-Procedure | 12 months | Rutherford Category 5 | 5 Participants |
Primary
Device Success
Device success was defined as the ability to achieve successful delivery and deployment of the drug-coated balloon (DCB) to the target lesion as described per Instructions for Use (IFU) within 3 minutes of insertion without removal and use of an additional device. The percentage of success was based on the number of DCB devices used.
Time frame: During the procedure
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| OA With Adjunctive DCB Angioplasty | Device Success | 42 Drug Coated Balloons |
| DCB Angioplasty | Device Success | 39 Drug Coated Balloons |
Primary
Freedom From Clinically-Driven Target Lesion Revascularization (CD-TLR) at 6 Months and 12 Months Post-Procedure
A Kaplan-Meier analysis was performed to determine the percent probability that a study participant was free from CD-TLR through 6 months and 12 months.
Time frame: 6 months and 12 months post-procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OA With Adjunctive DCB Angioplasty | Freedom From Clinically-Driven Target Lesion Revascularization (CD-TLR) at 6 Months and 12 Months Post-Procedure | Freedom from CD-TLR at 6 months | 96.8 % probability |
| OA With Adjunctive DCB Angioplasty | Freedom From Clinically-Driven Target Lesion Revascularization (CD-TLR) at 6 Months and 12 Months Post-Procedure | Freedom from CD-TLR at 12 months | 86.4 % probability |
| DCB Angioplasty | Freedom From Clinically-Driven Target Lesion Revascularization (CD-TLR) at 6 Months and 12 Months Post-Procedure | Freedom from CD-TLR at 6 months | 94.1 % probability |
| DCB Angioplasty | Freedom From Clinically-Driven Target Lesion Revascularization (CD-TLR) at 6 Months and 12 Months Post-Procedure | Freedom from CD-TLR at 12 months | 91.0 % probability |
Primary
Freedom From Major Adverse Events (MAEs) at 6 Months and 12 Months Post-Procedure
A Kaplan-Meier analysis was performed to determine the percent probability that the study participant was free from a major adverse event (MAE) through 6 months and 12 months. Major adverse events were defined as: clinically-driven target lesion revascularization (CD-TLR); unplanned, unavoidable major amputation of the index limb; and death within 30 days of the index procedure.
Time frame: 6 months and 12 months post-procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OA With Adjunctive DCB Angioplasty | Freedom From Major Adverse Events (MAEs) at 6 Months and 12 Months Post-Procedure | Freedom from MAE at 6 months | 90.6 % probability |
| OA With Adjunctive DCB Angioplasty | Freedom From Major Adverse Events (MAEs) at 6 Months and 12 Months Post-Procedure | Freedom from MAE at 12 months | 77.7 % probability |
| DCB Angioplasty | Freedom From Major Adverse Events (MAEs) at 6 Months and 12 Months Post-Procedure | Freedom from MAE at 6 months | 91.2 % probability |
| DCB Angioplasty | Freedom From Major Adverse Events (MAEs) at 6 Months and 12 Months Post-Procedure | Freedom from MAE at 12 months | 85.3 % probability |
Primary
Freedom From Unplanned, Unavoidable Major Amputation of the Index Limb at 6 Months and 12 Months Post-Procedure
A Kaplan-Meier analysis was performed to determine the percent probability that the study participant was free from an unplanned, unavoidable major amputation of the index limb through 6 months and 12 months.
Time frame: 6 months and 12 months post-procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OA With Adjunctive DCB Angioplasty | Freedom From Unplanned, Unavoidable Major Amputation of the Index Limb at 6 Months and 12 Months Post-Procedure | Freedom from major amputation at 6 months | 100.0 % probability |
| OA With Adjunctive DCB Angioplasty | Freedom From Unplanned, Unavoidable Major Amputation of the Index Limb at 6 Months and 12 Months Post-Procedure | Freedom from major amputation at 12 months | 96.6 % probability |
| DCB Angioplasty | Freedom From Unplanned, Unavoidable Major Amputation of the Index Limb at 6 Months and 12 Months Post-Procedure | Freedom from major amputation at 6 months | 100.0 % probability |
| DCB Angioplasty | Freedom From Unplanned, Unavoidable Major Amputation of the Index Limb at 6 Months and 12 Months Post-Procedure | Freedom from major amputation at 12 months | 100.0 % probability |
Primary
Patency of the Target Lesion at 6 Months and 12 Months Post-Procedure
Patency of the target lesion as reported by the Duplex Ultrasound (DUS) Core Laboratory. Vessel patency at 6 months and 12 months by Duplex Ultrasound (DUS), where patency is defined as \<50% restenosis within the treated lesion area. Patency was assessed by the DUS Core Laboratory.
Time frame: 6 months and 12 months post-procedure
Population: Lesions with available data for patency assessment by the DUS Core Lab
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| OA With Adjunctive DCB Angioplasty | Patency of the Target Lesion at 6 Months and 12 Months Post-Procedure | Patency at 12 months | 15 Lesions |
| OA With Adjunctive DCB Angioplasty | Patency of the Target Lesion at 6 Months and 12 Months Post-Procedure | Patency at 6 months | 15 Lesions |
| DCB Angioplasty | Patency of the Target Lesion at 6 Months and 12 Months Post-Procedure | Patency at 6 months | 5 Lesions |
| DCB Angioplasty | Patency of the Target Lesion at 6 Months and 12 Months Post-Procedure | Patency at 12 months | 6 Lesions |