RÉSUMÉ
Background:Inclisiran is a cholesterol-lowering small interfering RNA treatment licensed in the UK for lowering low-density lipoprotein cholesterol (LDL-C). VICTORION-Spirit (NCT04807400) is an implementation science study designed to provide evidence for inclisiran implementation within the National Health Service. The aim was to describe the process of patient identification employed in VICTORION-Spirit.Methods:A Phase IIIb, multicentre, randomisedcontrolled study, VICTORION-Spirit is evaluating inclisiran implementation in participants with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents and elevated LDL-C. Feasibility Assessment and Recruitment System for Improving Trial Efficiency (FARSITE) software utilising natural language search functions identified patients who may benefit from inclisiran. FARSITE searches were performed within Salford, Manchester, Trafford and Bury Clinical Commissioning Groups to identify individuals with elevated LDL-C or total cholesterol and pre-existing cardiovascular disease (CVD) or at risk of ASCVD.Results:FARSITE used ‘total cholesterol >4 mmol/l’ terminology rather than ‘LDL-C’; the former yielded >3 times the number of eligible patients. The search for individuals with pre-existing CVD identified 24,196 people in a population of 560,969 (4.3%); including ‘total cholesterol >4 mmol/l’ identified 10,431 individuals with pre-existing CVD and elevated total cholesterol. Searches for individuals at risk of ASCVD identified 65,457 people, narrowing to 26,580 at risk of ASCVD plus elevated total cholesterol. The most discriminatory SNOMED concept codes and their prevalence within the dataset can inform national approaches to develop similar searches. Conclusions: FARSITE searches employed in VICTORION-Spirit identified a population at risk of ASCVD in Greater Manchester, England, who may benefit from a cholesterol-lowering medication such as inclisiran.
RÉSUMÉ
Background: Translational gaps exist in implementing health innovations rapidly in clinical practice. Pragmatic effectiveness and implementation studies, therefore, play a pivotal role in understanding how high-value health innovations could be deployed and delivered in healthcare systems to reduce barriers to adoption and provide more rapid patient benefit. VICTORION-Spirit is an ongoing pragmatic, 9-month, phase IIIb, open-label, multicentre, randomised controlled study evaluating the implementation, patient experience, and delivery of the subcutaneous lipid-lowering therapy, inclisiran sodium 300 mg, in participants with elevated low-density lipoprotein cholesterol (LDL-C) who are on established lipid-lowering medication, or have been recommended lipid-lowering therapy but are unable to tolerate treatment. Methods: VICTORION-Spirit utilises a type 1 hybrid effectiveness-implementation design, where the primary objective is to demonstrate superiority of inclisiran with or without (±) behavioural support versus standard of care (SOC; e.g., statin and/or other lipid-lowering therapies) + behavioural support in terms of percentage reduction in LDL-C from baseline to Day 270 in a primary care setting. Secondary objectives will evaluate implementation of inclisiran ± behavioural support versus SOC + behavioural support through assessment of: patient satisfaction and patient activation/empowerment after treatment at Day 90; adherence to cardiovascular disease self-management; and serious adverse event profile. Additionally, a process evaluation ascertaining the views of: patients, providers, and National Health Service (NHS) commissioners will explore barriers and enablers to integrating inclisiran within primary care. Conclusions: The results of VICTORION-Spirit have potential to change our approach to lipid management and inform further implementation efforts in healthcare systems, such as the NHS. Trial registration: ClinicalTrials.gov NCT04807400.