LIMb: Leg Ischaemia Management Collaboration

Sponsor

University of Leicester (Other)

Overall Status

Recruiting

CT.gov ID

NCT04027244

Collaborator

University Hospitals, Leicester (Other), National Institute for Health Research, United Kingdom (Other), The George Davies Charitable Trust (Other)

420

Enrollment

Location

144

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Peripheral Arterial Disease Critical Limb Ischemia Frailty Cognitive Impairment Coronary Artery Disease

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 Design

Study Type:

Observational

Anticipated Enrollment :

420 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Leg Ischaemia Management Collaboration

Actual Study Start Date :

May 10, 2019

Anticipated Primary Completion Date :

May 9, 2022

Anticipated Study Completion Date :

May 9, 2031

Arms and Interventions

Arm	Intervention/Treatment
Primary cohort Any patient presenting to the Leicester Vascular Institute with SLI during the 2 year recruitment period (minimum 420 patients).
Frailty & cognitive additional assessments Any patient recruited to the primary cohort aged ≥65 years and undergoing an intervention for SLI (minimum 150 patients, target 210 patients).
Cardiac MRI additional assessments Any patient recruited to the primary cohort, with capacity to consent and undergoing an intervention for SLI (minimum 100 patients).
Biomarkers additional assessments Any patient recruited to the primary cohort and undergoing an intervention for SLI (no target recruitment set).
Historical cohort Retrospectively identified cohort of patients presenting to the study site with SLI between 2013 -15 (target 420).

Outcome Measures

Primary Outcome Measures

12 month amputation rate [12 months post recruitment]
Proportion of patients undergoing major lower limb amputation

Secondary Outcome Measures

Amputation free survival [≥12 months post recruitment]
Composite outcome measure of death or amputation
All-cause mortality [≥12 months]
Death from any cause
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)
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
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).

Other Outcome Measures

Cognitive impairment (Frailty & Cognitive additional assessments only) [Baseline, 3 and 12 months]
Prevalence of cognitive impairment as detected by the Montreal Cognitive Assessment (MoCA) Score 0-30; highger score = greater level of cognitive function Results will also be reported dichotomised to normal (score ≥24) and cognitive impairment (score ≤23)
Post-operative delirium (Frailty & Cognitive additional assessments only) [24 and 72 hours post intervention]
Incidence of post-operative delirium as detected by the Single Question in Delirium (SQiD) +/- 4 A's Test for delirium (4AT)
Prevalence of coronary artery disease (Cardiac MR additional assessments only) [Baseline]
Prevalence of coronary artery disease as detected by stress cardiac MRI
Incidence of peri-operative myocardial infarction (Cardiac MR additional assessments only) [2-4 months post intervention]
Incidence of peri-operative myocardial infarction as detected by cardiac MRI
Edmonton Frail Scale (Frailty & Cognitive additional assessments only) [Baseline, 3 and 12 months]
Prevalence and degree of frailty as measured by the Edmonton Frail Scale (EFS) Score 0-17, 0-5 = not frail, 6-7 = vulnerable, 8-9 = mild frailty, 10-11 = moderate frailty, 12-17 = severe frailty Results will also be reported dichotomised to frail (score ≥8) and non-frail (score ≤7)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 110 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

PRIMARY COHORT

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