Clinical trial NCT04027244: Leg Ischaemia Management Collaboration
Official title: Leg Ischaemia Management Collaboration
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Peripheral Arterial Disease
Critical Limb Ischemia
Frailty
Cognitive Impairment
Coronary Artery Disease
Keywords: Peripheral arterial disease
Limb salvage
Frailty
Cognitive dysfunction
Myocardial perfusion imaging
Biomarkers
Lead sponsor: University of Leicester
Sponsor class: OTHER
Collaborators: name: University Hospitals, Leicester
name: National Institute for Health Research, United Kingdom
name: The George Davies Charitable Trust
First posted: 2019-07-19
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: As representative a sample of patients presenting to the Leicester Vascular Institute with SLI during the study period as possible. All patients presenting with SLI within the age criteria will be eligible and personal consultee consent will allow recruitment even of those patients lacking capacity to consent.

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.

Eligibility criteria: 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

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

Exclusion criteria:

* Nil additional

Primary outcomes:
measure: 12 month amputation rate
timeFrame: 12 months post recruitment
Secondary outcomes:
measure: Amputation free survival
timeFrame: ≥12 months post recruitment
measure: All-cause mortality
timeFrame: ≥12 months
measure: Quality of life
timeFrame: 12 and 24 months post recruitment
measure: Disability
timeFrame: 12 and 24 months post recruitment
measure: Clinical Frailty Scale
timeFrame: Baseline, 12 and 24 months
measure: Anxiety & Depression
timeFrame: Baseline, 12 and 24 months
Other outcomes:
measure: Cognitive impairment (Frailty & Cognitive additional assessments only)
timeFrame: Baseline, 3 and 12 months
measure: Post-operative delirium (Frailty & Cognitive additional assessments only)
timeFrame: 24 and 72 hours post intervention
measure: Prevalence of coronary artery disease (Cardiac MR additional assessments only)
timeFrame: Baseline
measure: Incidence of peri-operative myocardial infarction (Cardiac MR additional assessments only)
timeFrame: 2-4 months post intervention
measure: Edmonton Frail Scale (Frailty & Cognitive additional assessments only)
timeFrame: Baseline, 3 and 12 months
Locations:
city: Leicester
country: United Kingdom
facility: Glenfield Hospital Leicester
state: Leicestershire
Study officials:
affiliation: University of Leicester
name: Rob D Sayers, MD
role: STUDY_CHAIR
References:
citation: Houghton JSM, Nduwayo S, Nickinson ATO, Payne TJ, Sterland S, Nath M, Gray LJ, McMahon GS, Rayt HS, Singh SJ, Robinson TG, Conroy SP, Haunton VJ, McCann GP, Bown MJ, Davies RSM, Sayers RD. Leg ischaemia management collaboration (LIMb): study protocol for a prospective cohort study at a single UK centre. BMJ Open. 2019 Sep 3;9(9):e031257. doi: 10.1136/bmjopen-2019-031257.