Invited speaker presentation The Joint Annual Meeting of the Stroke Society of Australasia (SSA) and Smartstrokes 2023

Keynote: Inflammation and Stroke events – an unresolved controversy (the CASPER Trial) (#240)

Geoffrey C Cloud 1 , Sanjay Patel 2 , Carlos Garcia‐Esperon 3 , John Simes 4 , Rachael Morton 4 , Andrzej Januszewski 4 , Val Gebski 4 , Kristy Robledo 4 , Geoffrey Donnan 5 , Vincent Thijs 6 , Graeme Hankey 7 , Mark Parsons 8 , Alicia Jenkins 9 , Rebecca Mister 4 , Anthony Keech 4 , Anthony Keech 4
  1. Alfred Health, Melbourne, VICTORIA, Australia
  2. Heart Research Institute, , The University of Sydney, Sydney, NSW, Australia
  3. Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia
  4. NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
  5. Department of Neurology, Royal Melbourne Hospital, Melbourne, Vic, Australia
  6. Stroke Theme, Florey Institute of Neuroscience and Mental Health, , University of Melbourne, Mlebourne, Vic, Australia
  7. Medical School, Faculty of Health and Medical Sciences, , The University of Western Australia, Nedlands, WA, Australia
  8. The Ingham Institute of Applied Medical Research, University of New South Wales South Western Clinical School, Liverpool, NSW, Australia
  9. Diabetes and Vascular Medicine Laboratory, Baker Heart and Diabetes Institute, Melbourne, Vic, Australia

Background: Inflammation (best identified by persistently elevated highly sensitive C-reactive protein or hs-CRP) is a key driver of ischaemic stroke (IS) pathogenesis in both large and small- vessel stroke. Colchicine has been proven to reduce inflammation in vulnerable coronary plaques and reduce recurrent atherosclerotic events but there is little evidence of its benefit in IS secondary prevention. We hypothesise that addition of Colchicine to optimal medical therapy (OMT) in patients post-Stroke, who have biomarker evidence of persistent inflammation, will reduce recurrent cardiovascular events.

Aims: To assess the effect of Colchicine (0.5 mg/day) in addition to OMT on Cardiovascular (CV) outcomes in participants post IS/ transient ischemic attack (TIA) with persistent vascular inflammation.

Methods: Phase III, randomised (1:1), double-blind, placebo-controlled, multi-centre superiority trial.  1500 adults with an IS event (defined as non-haemorrhagic, non-cardiac and non-fatal) without major disability (modified Rankin score [mRS] ≤3) OR clinical TIA with brain imaging evidence of acute infarction and hs-CRP ≥2mg/L at 4-52 weeks post-index event will be recruited, from 30 centres throughout Australia. A single-blind (unknown to the participant) ‘run-in phase’ of Colchicine 0.5mg tablet daily for 28 days precedes randomisation to long-term double-blind Colchicine 0.5mg or matched placebo tablets once daily with at least 36 months follow up and until the requisite total 420 CV events have accrued.

Results: The primary outcome is major adverse cardiovascular events (MACE); a composite of non-fatal stroke, Acute Coronary Syndrome (ACS), urgent unscheduled revascularisation and CV death. Secondary outcome measures include the individual components of MACE, health related quality of life and cost effectiveness measures.

Conclusion: This is the first RCT of low dose colchicine for secondary prevention in IS with persistent raised hs-CRP and is funded by the Australian MRFF.