Best Endovascular vs. Best Surgical Therapy in Patients With Critical Limb Ischemia

Not Applicable

Completed

• Conditions: Critical Limb Ischemia

• Registration Number: NCT02060630
• Lead Sponsor: Carelon Research

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.

Study Timeline

• Study First Submitted: 2014-02-06
• Study First Submitted QC: 2014-02-11
• Study First Posted: 2014-02-12
• Study Start: 2014-08
• Status Verified: 2022-03
• Primary Completion: 2022-03-01
• Study Completion: 2022-03-01
• Last Update Submitted: 2023-04-03
• Last Update Posted: 2023-04-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1843

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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: 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 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 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 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: 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 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
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
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
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: 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 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 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: 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
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 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
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: 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, 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
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 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
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 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, 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, 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: 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
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
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: 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: 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 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, 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
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
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
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
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

Trial Locations

Locations (160)

The University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Arizona Heart Hospital; 🇺🇸 Phoenix, Arizona, United States

University of Arizona - Banner University Medical Center; 🇺🇸 Tucson, Arizona, United States

Carondelet Heart & Vascular Institute; 🇺🇸 Tucson, Arizona, United States

University of Arkansas for Medical Services; 🇺🇸 Little Rock, Arkansas, United States

University of California - Irvine; 🇺🇸 Irvine, California, United States

San Diego VAMC; 🇺🇸 La Jolla, California, United States

UC San Diego Sulpizio Cardiovascular Center; 🇺🇸 La Jolla, California, United States

Loma Linda University Medical Center; 🇺🇸 Loma Linda, California, United States

Loma Linda VA Medical Center; 🇺🇸 Loma Linda, California, United States

Scroll for more (150 remaining)