Protocol: The Lacunar Intervention Trial 2 (LACI-2). A trial of two repurposed licenced drugs to prevent progression of cerebral small vessel disease. Link to paper on SAGE journals Authors Joanna Wardlaw, Philip M W Bath, Fergus Doubal, Anna Heye, Nikola Sprigg, Lisa J Woodhouse, Gordon Blair, Jason Appleton, Vera Cvoro, Timothy England, Ahamad Hassan, David John Werring, Alan Montgomery, The LACI-2 Trial Investigators Abstract Background: Small vessel disease causes a quarter of ischaemic strokes (lacunar subtype), up to 45% of dementia either as vascular or mixed types, cognitive impairment & physical frailty. However, there is no specific treatment to prevent progression of small vessel disease. Aim: We designed the LACunar Intervention Trial-2 (LACI-2) to test feasibility of a large trial testing cilostazol &/or isosorbide mononitrate (ISMN) by demonstrating adequate participant recruitment & retention in follow-up, drug tolerability, safety & confirm outcome event rates required to power a phase 3 trial. Methods & design: LACI-2 is an investigator-initiated, prospective randomised open label blinded endpoint (PROBE) trial aiming to recruit 400 patients with prior lacunar syndrome due to a small subcortical infarct. We randomise participants to cilostazol v no cilostazol & ISMN or no ISMN, minimising on key prognostic factors. All patients receive guideline-based best medical therapy. Patients commence trial drug at low dose, increment to full dose over 2–4 weeks, continuing on full dose for a year. We follow-up participants to one year for symptoms, tablet compliance, safety, recurrent vascular events, cognition & functional outcomes, Trails B & brain MRI. LACI-2 is registered ISRCTN 14911850, EudraCT 2016–002277-35. Trial outcome: Primary outcome is feasibility of recruitment & compliance; secondary outcomes include safety (cerebral or systemic bleeding, falls, death), efficacy (recurrent cerebral & cardiac vascular events, cognition on TICS, Trails B) & tolerability. Summary: LACI-2 will determine feasibility, tolerability & provide outcome rates to power a large phase 3 trial to prevent progression of cerebral small vessel disease. Keywords Cilostazol Isosorbide mononitrate Lacunar stroke Randomised clinical trial Small vessel disease (SVD) Related links Link to paper on SAGE journals Professor Joanna Wardlaw Dr Fergus Doubal The LACI-2 Trial Brain & nervous system Small vessel disease (SVD) Stroke Dementia 24 Apr 19. New stroke drug 23 May 18. New trial for stroke - LACI-2 02 Nov 17. LACI-1 trial complete Publication date 15 Jun, 2020
