Implementation of inclisiran in UK primary care for patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents: rationale and design of VICTORION-Spirit, a pragmatic phase IIIb, randomised controlled study

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.