Leg Ischaemia Management Collaboration

Recruiting

• Conditions: Peripheral Arterial Disease; Frailty; Critical Limb Ischemia; Cognitive Impairment; Coronary Artery Disease

• Registration Number: NCT04027244
• Lead Sponsor: University of Leicester

Brief Summary

Single-centre prospective cohort study of patients presenting with severe limb ischaemia (SLI). The primary outcome measure will be 12 month major amputation rate. A historical cohort of patients identified retrospectively will be the comparitor group used to assess the impact of a newly-established rapid-access limb salvage clinic.

Primary aim:

- Determine the proportion of patients with SLI undergoing major lower limb amputation within 12 months of presentation.

Secondary aims:

* Assess clinically important short-, medium- and long-term outcomes in those undergoing and not undergoing amputation

* Prevalence and degree of frailty and cognitive impairment

* Pevalence and degree of cardiac disease (detected by stress MRI)

* Establish a biobank for future biomarker analysis

* Investigate the role of frailty and cognitive assessments, cardiac MRI and biomarkers in risk-stratification of patients with SLI

Detailed Description

Severe limb ischaemia (SLI) is the end-stage of peripheral arterial occlusive disease (PAOD) whereby the viability of the limb is threatened due to the degree of arterial disease and subsequent ischaemia in the peripheral tissues. It is defined as ischaemic rest pain (or night pain) and/or ulceration or gangrene in the affected limb(s) for a minimum of two weeks attributed to confirmed PAOD. Treatment includes open surgical and endovascular revascularisation, with or without surgical debridement of affected tissues, amputation of toes and drainage of sepsis. In some patients revascularisation is not possible or fails resulting in the person requiring a major lower limb amputation.

Over 4000 major lower limb amputations per year were undertaken in England alone between 2003 and 2013 and a diabetes-related major lower limb amputation is performed every 30 seconds world-wide. As many as 25% of people with SLI will undergo a major lower limb amputation in the first year after presentation. Amputation negatively affects quality of life due to its negative impact on mobility, independence and ability to carry out activities of daily living.

This single-centre prospective cohort study will investigate the amputation rate at one year in patients presenting with SLI and compare this to a retrospectively identified historical cohort. This study will also investigate the prevelance and degree of frailty, cognitive impairment, and cardiac disease (detected by cardiac magnetic resonance imaging (MRI)), as well as establish a biobank for future biomarker analyses. The role of frailty and cognitive assessments, cardiac MRI and biomarker analysis in risk-stratifying patients with SLI will also be investigated.

Study Timeline

• Study Start: 2019-05-10
• Study First Submitted: 2019-07-11
• Study First Submitted QC: 2019-07-18
• Study First Posted: 2019-07-19
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-03
• Last Update Posted: 2020-11-04
• Primary Completion: 2022-05-09
• Study Completion: 2031-05-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 420

Inclusion Criteria

• All patients presenting to the Leicester Vascular Institute with SLI

Exclusion Criteria

• SLI not caused by PAOD
• Patients undergoing intervention during their index presentation prior to recruitment
• Patients lacking capacity to consent with no accompanying next of kin, relative, partner or friend who can act as a personal consulted
• Patients who cannot read, write or understand English
• Any significant disease or disorder which may either put the patient at risk because of participation in the study, or may influence the results of the study or the patient's ability to participate in the study

FRAILTY & COGNITIVE ADDITIONAL ASSESSMENTS

Inclusion criteria:

• Patients recruited to the primary cohort in whom a decision has been made to undergo an intervention for SLI
• Patients aged ≥65 years

Exclusion criteria:

• Nil additional

CARDIAC MRI ADDITIONAL ASSESSMENTS

Inclusion criteria:

• Patients recruited to the primary cohort in whom a decision has been made to undergo an intervention

Exclusion criteria:

• Absolute contraindications to cardiac MRI (Pregnancy, Non-MR safe permanent pacemaker, implanted cardiac defibrillator, intra-auricular implant or intra-cranial clips, severe claustrophobia, unstable angina)
• Contraindication to gadolinium contrast agent (Known adverse reaction, chronic renal failure (eGFR <30mL/min/1.73m^2))
• Patients lacking capacity to consent for cardiac MRI

BIOMARKERS ADDITIONAL ASSESSMENTS

• Patients recruited to the primary cohort in whom a decision has been made to undergo an intervention

Exclusion criteria:

• Nil additional

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
12 month amputation rate	12 months post recruitment	Proportion of patients undergoing major lower limb amputation

Secondary Outcome Measures

Name	Time	Method
All-cause mortality	≥12 months	Death from any cause
Disability	12 and 24 months post recruitment	Level of disability as measured by the Barthel Index; - Score 0-20; higher score = greater degree of functional independence/lower level of disability
Quality of life	12 and 24 months post recruitment	Quality of life as measured by the Vascular Quality of Life questionnaire (VascuQoL); * 25 item questionnaire, score 1-7 for each item, higher score = better quality of life; * Domains: activities (8 items), symptoms (4 items), pain (4 items), social (2 items) and emotional (7 items); each scored 1-7 (total of domain item scores/number of items); * Overall score 1-7 (total item score/25)
Amputation free survival	≥12 months post recruitment	Composite outcome measure of death or amputation
Clinical Frailty Scale	Baseline, 12 and 24 months	Prevalence and degree of frailty as measured by the Clinical Frailty Scale (CFS); * Score 1-9, higher score = greater degree of frailty; * Results will also be reported dichotomised to frail (score ≥5) and non-frail (score ≤4)
Anxiety & Depression	Baseline, 12 and 24 months	Prevalence and degree of anxiety and depression as measured by the Hospital Anxiety and Depression Scale (HADS); * 14 item questionnaire; score 0-3 for each item, higher score = more severe anxiety/depression; * Domains: Depression (7 items), Anxiety (7 items); each scored 0-21; 0-7 = normal, 8-10 = bordeline, 11-21 = abnormal (case).

Trial Locations

Locations (1)

Glenfield Hospital Leicester; 🇬🇧 Leicester, Leicestershire, United Kingdom