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Principal Investigator: Katharine L McGinigle
Organization: UNIV OF NORTH CAROLINA CHAPEL HILL
Fiscal Year: 2024
Award: $116,625
Funding agency: National Heart Lung and Blood Institute
PROJECT SUMMARY
This proposed study will comprehensively stage individual disease burden and mortality risk
at initial diagnosis and across the course of care for patients with chronic limb threatening
ischemia (CLTI). This debilitating, progressive condition is the most severe form of peripheral
artery disease, and successful treatment requires ongoing combinations of endovascular or
open revascularization, medical and wound/podiatric care. Because CLTI manifests in the
extremities, limb-based classification systems like the existing Wound, Ischemia, and foot
Infection (WIfI) staging system are important tools; however, the goals for CLTI treatment are
often broader than limb salvage and include freedom from recurrent disease and survival.
Despite the availability of multiple life- and limb-preserving treatments, success in improving
health outcomes of patients afflicted with CLTI has been limited. The recently completed BEST-
CLI randomized controlled trial with 1830 adult participants determined that surgical vein bypass
is the most effective initial revascularization approach for patients with CLTI, but almost 10%
required re-intervention to maintain blood flow to the limb, 10% underwent major limb
amputation, and 33% died within two years. The need for frequent re-intervention for patients in
the BEST-CLI study demonstrates that long-term CLTI and survival outcomes are dependent on
the sequence of treatments beyond the initial revascularization strategy. Yet, how post-primary
revascularization treatment impacts outcomes among different types of patients is unknown.
Our proposed study addresses these limitations. Using precision medicine analytics and
machine learning, we will leverage the rich BEST-CLI trial data to identify clusters of limb
characteristics, anatomic patterns of atherosclerosis, and comorbidities that associate with
differing levels of CLTI-free survival. Moreover, with the BEST-CLI longitudinal patient
assessments, we will quantify the impact of different post-primary revascularization treatments
on CLTI-free survival. This study will provide a deeper understanding of the limb- and life-
preserving effect of different combinations of medical and surgical treatments over time,
especially among patients who do not respond to first-line surgical interventions. Together, our
results will help clinicians set expectations and, if warranted, change practice based on likely
CLTI-free survival at initial diagnosis and over the lifespan of each patient. In the future, the
evidence generated from our study will be incorporated into precision medicine clinical trials
such sequential multiple assignment randomized trials (SMARTs) for discovering and testing
optimal, individually tailored treatment regimens for CLTI.
Terms: <21+ years old><Active Follow-up><Address><Adult><Adult Human><Adverse Experience><Adverse event><Affect><Algorithms><Anatomic Sites><Anatomic structures><Anatomy><Arterial Obstruction><Arterial Occlusion><Artery Obstruction><Assessment instrument><Assessment tool><Atherosclerosis><Atherosclerotic Cardiovascular Disease><Blood Vessels><Blood flow><Bypass><Cardiac><Cardiovascular><Cardiovascular Body System><Cardiovascular Diseases><Cardiovascular Organ System><Cardiovascular system><Caring><Cessation of life><Characteristics><Cholesterol><Chronic><Chronic Care><Classification><Clinical><Complex><Data><Death><Diabetes Mellitus><Diagnosis><Disease><Disease Progression><Disorder><Drugs><ESRD><End stage renal failure><End-Stage Kidney Disease><End-Stage Renal Disease><Event><Extremities><Freedom><Future><Goals><Health><Heart Vascular><Hypertension><Individual><Infection><Intervention><Intervention Strategies><Ischemia><Knowledge><Liberty><Life><Limb Salvage><Limb structure><Limbs><Lower Extremity><Lower Limb><Machine Learning><Measures><Medical><Medication><Membrum inferius><Modeling><NHLBI><National Heart, Lung, and Blood Institute><Non-Trunk><Operative Procedures><Operative Surgical Procedures><Outcome><Participant><Patient Care><Patient Care Delivery><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pattern><Perioperative><Peripheral arterial disease><Persons><Pharmaceutical Preparations><Phenotype><Prevalence><Process><Randomized, Controlled Trials><Recommendation><Recurrent disease><Relapsed Disease><Reporting><Research><Research Support><Risk><Risk Assessment><Saphenous Vein><Sequential Multiple Assignment Randomized Trial><Smoke><Staging><Staging System><Strategic vision><Surgical><Surgical Interventions><Surgical Procedure><System><Systematics><Testing><Tibial Arteries><Time><Treatment Protocols><Treatment Regimen><Treatment Schedule><United States><Update><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Veins><Woman><Work><active followup><adulthood><amputated limb><artery occlusion><atheromatosis><atherosclerotic disease><atherosclerotic vascular disease><burden of disease><burden of illness><cardiovascular disorder><care for patients><care of patients><caring for patients><circulatory system><co-morbid><co-morbidity><cohort><comorbidity><customized therapy><customized treatment><death risk><diabetes><disease burden><drug/agent><expectation><femoral artery><follow up><follow-up><followed up><followup><foot><group of color><high blood pressure><high risk><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><improved><individual of color><individualized medicine><individualized patient treatment><individualized therapeutic strategy><individualized therapy><individualized treatment><interventional strategy><life span><lifespan><limb amputation><limb loss><lost limb><machine based learning><mortality><mortality risk><non-healing wounds><nonhealing wounds><older adult><older adulthood><patient oriented outcomes><patient response><patient specific response><patient specific therapies><patient specific treatment><people of color><peripheral artery disease><persistent wounds><person of color><population of color><precision medicine><precision medicine clinical trials><precision-based medicine><preservation><randomized control trial><response to therapy><response to treatment><responsive patient><revascularization><secondary analysis><success><surgery><survival outcome><tailored medical treatment><tailored therapy><tailored treatment><therapeutic response><therapy response><tissue wound><tobacco abuse><tool><treat wound><treatment pattern><treatment response><treatment responsiveness><unique treatment><vascular><wound><wound assessment><wound care><wound management><wound monitoring><wound therapeutics><wound therapy><wound treatment><wounding><wounds>