Critical Limb Ischemia (CLI)
Conditions
Keywords
Infrapopliteal lesions, Esprit BTK Everolimus Eluting Bioresorbable Scaffold System, Percutaneous transluminal angioplasty (PTA), ABT-CIP-10293
Brief summary
The objective of this prospective, single-blinded, randomized controlled clinical investigation is to evaluate the safety and efficacy of the everolimus eluting Esprit BTK System for the planned treatment of narrowed infrapopliteal lesions. Approximately 225 subjects will be randomized in a 2:1 ratio. The clinical investigation will be conducted at approximately 65 clinical sites in the US, Asia, Australia, and New Zealand.
Interventions
DEVICEEsprit BTK Device
Participants will receive Esprit BTK Device
Participants will receive PTA treatment
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: 1. Subject must provide written informed consent prior to any clinical investigation related procedure. 2. Subject has symptomatic Critical Limb Ischemia (CLI), Rutherford Becker Clinical Category 4 or 5. 3. Subject requires primary treatment of up to two de novo or restenotic (treated with prior PTA) infrapopliteal lesions. 4. Subject must be at least 18 years of age. 5. Female subject of childbearing potential should not be pregnant and must be on birth control. Note: Female subjects of child-bearing potential must have a negative pregnancy test done within 7 days prior to the index procedure per site standard test. Anatomic Inclusion Criteria: 1. Up to two native infrapopliteal lesions, each lesion located in separate infrapopliteal vessel in the same limb. Restenotic (from prior PTA) lesions are allowed. 1. Lesion must be located in the proximal 2/3 of native infrapopliteal vessels, with vessel diameter of ≥ 2.5 mm and ≤ 4.00 mm by investigator visual assessment. 2. Total scaffold length to completely cover/treat a target lesion must not exceed 170 mm (total everolimus drug dose of 1790 µg). 3. The total scaffold length among all target lesions must not exceed 170 mm. 4. The target vessel cannot have any other angiographic significant lesions (≥50%). 5. Tandem lesions are allowed if they are \< 3 cm apart and the total scaffold length used to cover the entire diseased segment is ≤ 170 mm. Each tandem lesion is considered one lesion. 2. Target lesion(s) must have ≥ 70% stenosis, per visual assessment at the time of the procedure. If needed, quantitative imaging (angiography, IVUS, and/or OCT) can be used to aid accurate sizing of the vessels. 3. The distal margin of the target lesion must be located ≥ 10 cm proximal to the proximal margin of the ankle mortise. The vessel segment distal to the target lesion must be patent all the way to the ankle, with no significant lesion (≥ 50% stenosis). 4. Significant lesion (≥ 50% stenosis) in the inflow artery(ies) must be treated successfully (as per physician's assessment of the angiography) through standard of care prior to the treatment of the target lesion. Treatment can be done within the same trial procedure. 5. Non-target lesion(s) (if applicable) must be located in separate infrapopliteal vessel(s) from the target lesion, and suitable to be treated per institution standard of care. 6. Guidewire must cross the target lesion successfully. Crossing in an antegrade fashion is preferred, but retrograde crossing may be used. However, the treatment must be delivered antegrade.
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy Endpoint: Number of Participants With Composite of Limb Salvage and Primary Patency | At 1 year | This endpoint was to evaluate the effectiveness of the Esprit BTK System in maintaining patency (CD-TLR and binary restenosis), and at preventing catastrophic limb events such as total vessel occlusion or major amputation. Composite of Limb Salvage and Primary Patency included freedom from: above ankle amputation in index limb, 100% total occlusion of target vessel, binary restenosis of target lesion and clinically-driven target lesion revascularization (CD-TLR). |
| Primary Safety Endpoint: Freedom From Major Adverse Limb Event + Peri-Operative Death Rate (MALE + POD) | At 30 days (for POD) and 6 months (for MALE) | The primary safety endpoint assessed the safety of the devices used for treatment of below the knee lesions. It included freedom from MALE+POD (Major Adverse Limb Event + Peri-Operative Death). MALE includes above-ankle amputation in the index limb, major re-intervention on the index limb at 6 months and POD includes perioperative (30-day) mortality. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| First Powered Secondary Endpoint: Binary Restenosis of the Target Lesion | At 1 year | This endpoint was added to better evaluate the device performance as binary restenosis was used as a marker for disease progression over time. |
| Second Powered Secondary Endpoint: Freedom From Above Ankle Amputation in Index Limb, 100% Total Occlusion of the Target Vessel, and CD-TLR. | At 1 year | This endpoint was chosen as it was important to assess whether Esprit BTK System was efficacious at maintaining patency and preventing catastrophic limb events through 1 year. |
Countries
Australia, Hong Kong, New Zealand, Singapore, Taiwan, United States
Participant flow
Recruitment details
A total of 261 subjects from 50 sites were registered in the RCT population of the study including 88 in the PTA group and 173 in the Esprit BTK group up to 1-year follow-up, between August 18, 2020, and September 14, 2022.
Participants by arm
| Arm | Count |
|---|---|
| Esprit BTK Participants who receive Esprit BTK device will be included in this arm
Esprit BTK Device: Participants will receive Esprit BTK Device | 173 |
| Percutaneous Transluminal Angioplasty (PTA) Participants who receive PTA treatment will be included in this arm
Percutaneous Transluminal Angioplasty (PTA) Device: Participants will receive PTA treatment | 88 |
| Total | 261 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 12 | 6 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 3 |
Baseline characteristics
| Characteristic | Esprit BTK | Percutaneous Transluminal Angioplasty (PTA) | Total |
|---|---|---|---|
| Age, Continuous | 73.3 years STANDARD_DEVIATION 9.9 | 71.1 years STANDARD_DEVIATION 10.4 | 72.6 years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 31 Participants | 12 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 132 Participants | 70 Participants | 202 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 6 Participants | 16 Participants |
| Hypertension | 163 Participants | 80 Participants | 243 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 36 Participants | 11 Participants | 47 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 11 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 18 Participants | 7 Participants | 25 Participants |
| Race (NIH/OMB) White | 97 Participants | 56 Participants | 153 Participants |
| Sex: Female, Male Female | 56 Participants | 27 Participants | 83 Participants |
| Sex: Female, Male Male | 117 Participants | 61 Participants | 178 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 173 | 6 / 88 |
| other Total, other adverse events | 105 / 173 | 60 / 88 |
| serious Total, serious adverse events | 89 / 173 | 45 / 88 |
Outcome results
Primary
Primary Efficacy Endpoint: Number of Participants With Composite of Limb Salvage and Primary Patency
This endpoint was to evaluate the effectiveness of the Esprit BTK System in maintaining patency (CD-TLR and binary restenosis), and at preventing catastrophic limb events such as total vessel occlusion or major amputation. Composite of Limb Salvage and Primary Patency included freedom from: above ankle amputation in index limb, 100% total occlusion of target vessel, binary restenosis of target lesion and clinically-driven target lesion revascularization (CD-TLR).
Time frame: At 1 year
Population: Analysis excluded subjects who terminated from the study prior to the lower limit (337 days) of the 1-year primary efficacy endpoint follow-up window without any components of the primary endpoint, and subjects with no known endpoint event and who did not have analyzable duplex ultrasound or angiography for the 1-year imaging assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Esprit BTK | Primary Efficacy Endpoint: Number of Participants With Composite of Limb Salvage and Primary Patency | 111 Participants |
| Percutaneous Transluminal Angioplasty (PTA) | Primary Efficacy Endpoint: Number of Participants With Composite of Limb Salvage and Primary Patency | 31 Participants |
p-value: <0.0001One-sided Chi-square test
Primary
Primary Safety Endpoint: Freedom From Major Adverse Limb Event + Peri-Operative Death Rate (MALE + POD)
The primary safety endpoint assessed the safety of the devices used for treatment of below the knee lesions. It included freedom from MALE+POD (Major Adverse Limb Event + Peri-Operative Death). MALE includes above-ankle amputation in the index limb, major re-intervention on the index limb at 6 months and POD includes perioperative (30-day) mortality.
Time frame: At 30 days (for POD) and 6 months (for MALE)
Population: Analysis excluded subjects who terminated from the study prior to the lower limit (152 days) of the 6-month primary safety endpoint follow-up window without any components of the primary endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Esprit BTK | Primary Safety Endpoint: Freedom From Major Adverse Limb Event + Peri-Operative Death Rate (MALE + POD) | 155 Participants |
| Percutaneous Transluminal Angioplasty (PTA) | Primary Safety Endpoint: Freedom From Major Adverse Limb Event + Peri-Operative Death Rate (MALE + POD) | 85 Participants |
p-value: 0.0019Farrington-Manning non-inferiority (NI)
Secondary
First Powered Secondary Endpoint: Binary Restenosis of the Target Lesion
This endpoint was added to better evaluate the device performance as binary restenosis was used as a marker for disease progression over time.
Time frame: At 1 year
Population: Analysis excluded subjects who terminated from the study prior to the lower limit (337 days) of the 1-year primary efficacy endpoint follow-up window without any components of the primary endpoint, and subjects with no known endpoint event and who did not have analyzable duplex ultrasound or angiography for the 1-year imaging assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Esprit BTK | First Powered Secondary Endpoint: Binary Restenosis of the Target Lesion | 35 Participants |
| Percutaneous Transluminal Angioplasty (PTA) | First Powered Secondary Endpoint: Binary Restenosis of the Target Lesion | 35 Participants |
p-value: <0.0001Chi-squared
Secondary
Second Powered Secondary Endpoint: Freedom From Above Ankle Amputation in Index Limb, 100% Total Occlusion of the Target Vessel, and CD-TLR.
This endpoint was chosen as it was important to assess whether Esprit BTK System was efficacious at maintaining patency and preventing catastrophic limb events through 1 year.
Time frame: At 1 year
Population: Analysis excluded subjects who terminated from the study prior to the lower limit (337 days) of the 1-year primary efficacy endpoint follow-up window without any components of the primary endpoint, and subjects with no known endpoint event and who did not have analyzable duplex ultrasound or angiography for the 1-year imaging assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Esprit BTK | Second Powered Secondary Endpoint: Freedom From Above Ankle Amputation in Index Limb, 100% Total Occlusion of the Target Vessel, and CD-TLR. | 124 Participants |
| Percutaneous Transluminal Angioplasty (PTA) | Second Powered Secondary Endpoint: Freedom From Above Ankle Amputation in Index Limb, 100% Total Occlusion of the Target Vessel, and CD-TLR. | 49 Participants |
p-value: 0.0081One-sided Chi-square test