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


  • Paul M. Wilson The University of Manchester, Manchester, UK
  • Samantha Dixon Novartis Pharmaceuticals UK Limited, London, UK
  • Tracey Vell Health Innovation Manchester, Manchester, UK
  • Peter Bower The University of Manchester, Manchester, UK
  • Linda Rootkin Novartis Latin America Services, Inc, Miami, FL, USA
  • Claire Williams NorthWest EHealth, Manchester, UK
  • Adam Strong Novartis Pharmaceuticals UK Limited, London, UK
  • David Lawrence Novartis Pharmaceuticals AG, Basel, Switzerland
  • Rebecca Elvey The University of Manchester, Manchester, UK
  • Owen Williams NorthWest EHealth, Manchester, UK
  • Norman Stein NorthWest EHealth, Manchester, UK
  • J. Martin Gibson The University of Manchester, Manchester, UK; NorthWest EHealth, Manchester, UK



Implementation science, Primary care, Population health, Protocol, Cardiovascular disease, Inclisiran


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: NCT04807400.


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