Critical Limb Ischemia
Conditions
Keywords
Surgical revascularization, Endovascular revascularization, Amputation, Peripheral artery disease, Critical limb ischemia, claudication, leg pain, leg ulcer, gangrene
Brief summary
This study will compare the effectiveness of best available surgical treatment with best available endovascular treatment in adults with critical limb ischemia (CLI) who are eligible for both treatment options.
Detailed description
Male and female subjects aged 18 years or older will be randomized to receive either open surgical treatment or endovascular treatment. They will be followed for at least 2 years and up to 4 years and 2 months after treatment to primarily assess survival and major adverse limb events in the index or treated limb, and secondarily, to determine clinical and cost effectiveness outcomes after treatment. These outcomes (survival-free of major limb events and clinical, functional and cost effectiveness) will be compared within two cohorts of subjects: those with an available single-segment great saphenous vein, and those with an alternative conduit. The null hypotheses for both cohorts is that there will be no difference in MALE-free survival between best endovascular therapy and best surgical therapy.
Interventions
PROCEDUREOpen surgical revascularization
A variety of FDA approved devices will be used within this treatment arm. The trial will submit a proof-of-concept IDE application to the FDA to cover all devices.
Sponsors
Carelon Research
Brigham and Women's Hospital
Massachusetts General Hospital
Boston Medical Center
National Heart, Lung, and Blood Institute (NHLBI)
Abbott
Bard Ltd
Boston Scientific Corporation
Cordis US Corp.
Abbott Medical Devices
Canadian Society for Vascular Surgery
Eastern Vascular Society
W.L.Gore & Associates
Midwest Vascular Society
New England Society for Vascular Surgery
Society for Clinical Vascular Surgery
Society for Interventional Radiology
Southern Vascular Society
Society for Vascular Medicine
Society for Vascular Surgery
Vascular and Endovascular Surgery Society
Vascular Interventional Advances
Western Vascular Society
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
1. Male or female, age 18 years or older. 2. Infrainguinal PAOD (occlusive disease of the arteries below the inguinal ligament). 3. CLI, defined as arterial insufficiency with gangrene, non-healing ischemic ulcer, or rest pain consistent with Rutherford categories 4-6. 4. Candidate for both endovascular and open infrainguinal revascularization as judged by the treating investigators 5. Adequate aortoiliac inflow. 6. Adequate popliteal, tibial or pedal revascularization target defined as an infrainguinal arterial segment distal to the area of stenosis/occlusion which can support a distal anastomosis of a surgical bypass. 7. Willingness to comply with protocol, attend follow-up appointments, complete all study assessments, and provide written informed consent.
Exclusion criteria
1. Presence of a popliteal aneurysm (\>2 cm) in the index limb. 2. Life expectancy of less than 2 years due to reasons other than PAOD. 3. Excessive risk for surgical bypass (as determined by the operating surgeon and the CLI Team) 4. Planned above ankle amputation on ipsilateral limb within 4 weeks of index procedure. 5. Active vasculitis, Buerger's disease, or acute limb-threatening ischemia 6. Any prior index limb infrainguinal stenting or stent grafting associated with significant restenosis within 1 cm of stent or stent-graft, unless the occlusion/restenosis site is outside the intended treatment zone (i.e.,. a tibial vessel that is not currently intended to be revascularized as a part of the treatment for CLI). 7. Any of the following procedures performed on the index limb within 3 months prior to enrollment: 1. Infrainguinal balloon angioplasty, atherectomy, stent, or stentgraft; 2. Infrainguinal bypass with either venous or prosthetic conduit 8. Open surgical inflow procedure (aortofemoral, axillofemoral, iliofemoral, thoracofemoral or femorofemoral bypass) within 6 weeks prior to enrollment 9. Current chemotherapy or radiation therapy. 10. Absolute contraindication to iodinated contrast due to prior near-fatal anaphylactoid reaction (laryngospasm, bronchospasm, cardiorespiratory collapse, or equivalent) which would preclude patient participation in angiographic procedures. 11. Pregnancy or lactation. 12. Administration of an investigational drug for PAD within 30 days of randomization. 13. Participation in a clinical trial (except observational studies) within the previous 30 days. 14. Prior enrollment or randomization into BEST-CLI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The primary efficacy endpoint: MALE (Major Adverse Limb Event)-free survival. MALE is defined as above ankle amputation of the index limb or major re-intervention (e.g. new bypass graft, jump/interposition graft revision, or thrombectomy/ thrombolysis) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | * Time to major adverse limb event or death, whichever occurs first in subjects with Single-Segment Great Saphenous Vein (SSGSV) available * Time to major adverse limb event or death, whichever occurs first in subjects without available SSGSV |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical: Re-intervention and amputation-free survival (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to re-intervention of the index leg, above ankle amputation of the index leg, or death, whichever occurs first in subjects without available SSGSV |
| Clinical: Freedom from MALE-POD (POD, defined as death within 30 days of index procedure) (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to re-intervention of the index leg, amputation of the index leg, or death within 30 days of index procedure, whichever occurs first in subjects with SSGSV available |
| Clinical: Clinical: Freedom from MALE-POD (POD, defined as death within 30 days of index procedure) (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to re-intervention of the index leg, amputation of the index leg, or death within 30 days of index procedure, whichever occurs first in subjects without available SSGSV |
| Clinical: Amputation-free survival (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to amputation of the index leg, or death, whichever occurs first in subjects with SSGSV available |
| Clinical: Amputation-free survival (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to amputation of the index leg, or death, whichever occurs first in subjects without available SSGSV |
| Clinical: Freedom from POD (POD, defined as death within 30 days of index procedure) (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to death within 30 days of index procedure in subjects with SSGSV available |
| Clinical: Freedom POD (POD, defined as death within 30 days of index procedure) (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to death within 30 days of index procedure in subjects without available SSGSV |
| Clinical: Freedom from Myocardial Infarction (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to myocardial infarction (MI) in subjects with SSGSV available |
| Clinical: Freedom from Myocardial Infarction (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to myocardial infarction (MI) in subjects without available SSGSV |
| Clinical: Freedom from Stroke (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to stroke in subjects with SSGSV available |
| Clinical: Freedom from Stroke (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to stroke in subjects without available SSGSV |
| Clinical: Freedom from re-intervention (major and minor) in index leg (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to re-intervention (major and minor) in index leg in subjects with SSGSV available |
| Clinical: Freedom from re-intervention (major and minor) in index leg (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to re-intervention (major and minor) in index leg in subjects without available SSGSV |
| Clinical: Number of re-interventions (major and minor) in per limb salvaged (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Number of re-interventions (major and minor) in per limb salvaged in subjects with SSGSV available |
| Clinical: Number of re-interventions (major and minor) in per limb salvaged (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Number of re-interventions (major and minor) in per limb salvaged in subjects without available SSGSV |
| Clinical: Freedom from hemodynamic failure (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to hemodynamic failure in subjects with SSGSV available |
| Clinical: Freedom from hemodynamic failure (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to hemodynamic failure in subjects without available SSGSV |
| Clinical: Freedom from clinical failure (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to above ankle amputation, major reintervention, MALE, degradation of WIfI stage or death, whichever occurs first in subjects with SSGSV available |
| Clinical: Freedom from clinical failure (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to above ankle amputation, major reintervention, MALE, degradation of WIfI stage or death, whichever occurs first in subjects without available SSGSV |
| Clinical: Freedom from Critical Limb Ischemia (CLI) (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to resolution of presenting CLI symptoms in the index limb in subjects with SSGSV available |
| Clinical: Freedom from Critical Limb Ischemia (CLI) (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to resolution of presenting CLI symptoms in the index limb in subjects without available SSGSV |
| Clinical: Freedom from all-cause mortality (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to all-cause mortality in subjects with SSGSV available |
| Clinical: Freedom from all-cause mortality (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to all-cause mortality in subjects without available SSGSV |
| Functional: Quality of Life assessment using VasuQoL (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | VasuQOL measurements in subjects with SSGSV available |
| Functional: Quality of Life assessment using VasuQoL (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | VasuQOL measurements in subjects without available SSGSV |
| Functional: Quality of Life assessment using EuroQoL (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | EuroQOL measurements in subjects with SSGSV available |
| Functional: Quality of Life assessment using EuroQoL (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | EuroQOL measurements in subjects without available SSGSV |
| Functional: Function assessment using SF-12, PCS (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Physical Component Summary (PCS) scores in subjects with SSGSV available |
| Functional: Function assessment using SF-12, PCS (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Physical Component Summary (PCS) scores in subjects without available SSGSV |
| Functional: Function assessment using SF-12, MCS (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Mental Component Summary (MCS) scores in subjects with SSGSV available |
| Functional: Function assessment using SF-12, MCS (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Mental Component Summary (MCS) scores in subjects without available SSGSV |
| Functional: Function assessment using SF-12, SF-6D R2 (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Utility Index (SF-6D R2) scores in subjects with SSGSV available |
| Functional: Function assessment using SF-12, SF-6D R2(cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Utility Index (SF-6D R2) scores in subjects without available SSGSV |
| Functional: Numerical rating scale for Pain, Pain Now (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Scores for Pain Now in subjects with SSGSV available |
| Functional: Numerical rating scale for Pain, Pain Now (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Scores for Pain Now in subjects without available SSGSV |
| Functional: Numerical rating scale for Pain, Usual level of Pain (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Scores for Usual level of Pain during the last week in subjects with SSGSV available |
| Functional: Numerical rating scale for Pain, Usual level of Pain (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Scores for Usual level of Pain during the last week in subjects without available SSGSV |
| Functional: Numerical rating scale for Pain, Best level of Pain (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Scores for Best level of Pain during the last week in subjects with SSGSV available |
| Clinical: Re-intervention and amputation-free survival (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Time to re-intervention of the index leg, above ankle amputation of the index leg, or death, whichever occurs first in subjects with SSGSV available |
| Functional: Numerical rating scale for Pain, Worst level of Pain (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Scores for Worst level of Pain during the last week in subjects with SSGSV available |
| Functional: Numerical rating scale for Pain, Worst level of Pain (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Scores for Worst level of Pain during the last week in subjects without available SSGSV |
| Function: Six-minute walk test (cohort 1) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Six-minute walk test measurements in subjects with SSGSV available. The six-minute walk test was performed at a subset of clinical sites (for whom this test was standard of care) and was limited to patients for whom rest pain, wounds, or foot surgery (recent or anticipated) did not preclude weight bearing |
| Function: Six-minute walk test (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Six-minute walk test measurements in subjects without available SSGSV. The six-minute walk test was performed at a subset of clinical sites (for whom this test was standard of care) and was limited to patients for whom rest pain, wounds, or foot surgery (recent or anticipated) did not preclude weight bearing |
| Functional: Numerical rating scale for Pain, Best level of Pain (cohort 2) | Through each subject's last regularly scheduled study visit, up to a maximum of 84 months per subject | Scores for Best level of Pain during the last week in subjects without available SSGSV |
Countries
Canada, Finland, Italy, New Zealand, United States
Outcome results
None listed