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Leg Ischaemia Management Collaboration (LIMb)

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ClinicalTrials.gov Identifier: NCT04027244
Recruitment Status : Recruiting
First Posted : July 19, 2019
Last Update Posted : November 4, 2020
Sponsor:
Collaborators:
University Hospitals, Leicester
National Institute for Health Research, United Kingdom
The George Davies Charitable Trust
Information provided by (Responsible Party):
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

Condition or disease
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.

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Study Type : Observational
Estimated Enrollment : 420 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Leg Ischaemia Management Collaboration
Actual Study Start Date : May 10, 2019
Estimated Primary Completion Date : May 9, 2022
Estimated Study Completion Date : May 9, 2031

Group/Cohort
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).



Primary Outcome Measures :
  1. 12 month amputation rate [ Time Frame: 12 months post recruitment ]
    Proportion of patients undergoing major lower limb amputation


Secondary Outcome Measures :
  1. Amputation free survival [ Time Frame: ≥12 months post recruitment ]
    Composite outcome measure of death or amputation

  2. All-cause mortality [ Time Frame: ≥12 months ]
    Death from any cause

  3. Quality of life [ Time Frame: 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)

  4. Disability [ Time Frame: 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


  5. Clinical Frailty Scale [ Time Frame: 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)

  6. Anxiety & Depression [ Time Frame: 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:
  1. Cognitive impairment (Frailty & Cognitive additional assessments only) [ Time Frame: 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)

  2. Post-operative delirium (Frailty & Cognitive additional assessments only) [ Time Frame: 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)

  3. Prevalence of coronary artery disease (Cardiac MR additional assessments only) [ Time Frame: Baseline ]
    Prevalence of coronary artery disease as detected by stress cardiac MRI

  4. Incidence of peri-operative myocardial infarction (Cardiac MR additional assessments only) [ Time Frame: 2-4 months post intervention ]
    Incidence of peri-operative myocardial infarction as detected by cardiac MRI

  5. Edmonton Frail Scale (Frailty & Cognitive additional assessments only) [ Time Frame: 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)


Biospecimen Retention:   Samples Without DNA
Serum and Plasma samples.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 110 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04027244


Contacts
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Contact: Rob D Sayers, MD +44 (0)116 252 3141 rs152@le.ac.uk
Contact: Tanya J Payne, BSc +44 (0)116 258 3867 tjp28@le.ac.uk

Locations
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United Kingdom
Glenfield Hospital Leicester Recruiting
Leicester, Leicestershire, United Kingdom, LE3 9QP
Contact: Tanya J Payne    +44 (0)116 358 3867    tjp28@le.ac.uk   
Principal Investigator: Rob D Sayers, MD         
Sub-Investigator: Matt J Bown, MD         
Sub-Investigator: Thompson G Robinson, MD         
Sub-Investigator: Gerry P McCann, MD         
Sub-Investigator: Victoria J Haunton, MD         
Sub-Investigator: Sally J Singh, PhD         
Principal Investigator: Robert SM Davies, MD         
Sub-Investigator: Tanya J Payne, BSc         
Sub-Investigator: Laura J Gray, PhD         
Sub-Investigator: Harjeet S Rayt, MD         
Sub-Investigator: Gregory S McMahon, MD         
Sponsors and Collaborators
University of Leicester
University Hospitals, Leicester
National Institute for Health Research, United Kingdom
The George Davies Charitable Trust
Investigators
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Study Chair: Rob D Sayers, MD University of Leicester
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT04027244    
Other Study ID Numbers: 0686
First Posted: July 19, 2019    Key Record Dates
Last Update Posted: November 4, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Anonymised dataset will be available on request to the Chief Investigator (Prof Rob Sayers). The study protocol will be published in an open-access journal prior to completion of recruitment.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Leicester:
Peripheral arterial disease
Limb salvage
Frailty
Cognitive dysfunction
Myocardial perfusion imaging
Biomarkers
Additional relevant MeSH terms:
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Coronary Artery Disease
Peripheral Arterial Disease
Peripheral Vascular Diseases
Ischemia
Frailty
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Atherosclerosis