PRACTISE - AF: Platform tRiAl to improve outComes afTer cardIac SurgEry – Atrial Fibrillation (Accelerator Award)

BACKGROUND

Post operative atrial fibrillation (POAF) is the most common complication after heart surgery, affecting around 1 in 3 people. POAF results from irregular, disorganized electrical activity in the heart, leading to rapid and ineffective contraction. An episode of POAF adds 12 to 24 hours to the intensive care unit (ICU) stay, 2-5 days to the hospital stay and almost triples in-hospital and 1-year mortality.

Although multiple interventions are available which may prevent POAF, none are embedded in clinical practice due to insubstantial evidence. AIMS AND OBJECTIVES

The overarching aim of the proposed Acceleration Award work will be to develop a future application for a platform clinical trial protocol investigating potential treatments to prevent POAF in patients undergoing cardiac surgery. The objectives and their respective work packages (WP) are to: 1) Define PICO (Population, Interventions, Comparator and Outcome) and estimands of interest (WP1); 2) Define the statistical design to inform the master protocol (WP2); 3) Develop research capacity and infrastructure (WP3); 4) Integrate knowledge from existing platform trials (WP4); 5) Assemble the PPI structure and develop the PPI plan for the platform trial (WP5); 6) Prepare and submit the Stage 1 application to the HTA (WP6).

METHODS

WP1 – Rapid scoping review of the evidence (including implementing an automation process to identify new studies); survey of cardiac surgery centres; and assembling an independent intervention prioritisation committee, who will consider evidence from the review and survey and identify interventions that will be tested in the platform study, the order in which they will be tested, a definition of standard care for the comparator arm, the estimands that will be considered, how the primary outcome (AF) will be measured, and the timeframe for measurement

WP2 – Develop the statistical design of the platform study through statistical simulations considering clinical scenarios, interventions and the estimands of interest (identified in WP1). Simulations will be presented to key stakeholders through summary reports and online meetings and a face-to-face meeting finalise the design.

WP3 – Build research capacity and identify a framework for participation in the platform trial, through engaging with pre-existing research networks via regular online meetings (including representation from international cardiac surgery centres).

WP4 – Integrate knowledge from existing platform trials by convening a face-to-face meeting to discuss how current operationalisation guidelines (from existing platform trials) can been applied to a cardiac surgery platform trial.

WP5 – Develop the PPI plan by establishing a PPI working group, framework for PPI involvement and PPI plan for the platform trial. The PPI working group will oversee all WPs.

WP6 – Write the draft master protocol, which will inform the development of a Stage 1 application to be submitted to the subsequent platform grant call in November 2023. DISSEMINATION AND ANTICIPATED RESULTS

We will communicate our findings in scientific journals and directly to patients and professionals the Society of Cardiothoracic Surgeons (SCTS), the Association for Cardiothoracic Anaesthetists and Critical Care (ACTACC), the British Heart Foundation (BHF) and the National Cardiac Surgery Trials Initiative and National PPI group.