Cilostazol and isosorbide mononitrate for the prevention of progression of cerebral small vessel disease: Baseline data and statistical analysis plan for the Lacunar Intervention Trial-2 (LACI-2) (ISRCTN14911850)

ABSTRACT Background Cerebral small vessel disease (SVD) causes lacunar strokes (25% of all ischaemic strokes), physical frailty and cognitive impairment and vascular and mixed dementia. There is no specific treatment to prevent progression of SVD. Methods The LACunar Intervention Trial-2 (LACI-2) is an investigator-initiated prospective randomised open-label blinded-endpoint (PROBE) phase II feasibility study assessing cilostazol and isosorbide mononitrate for preventing SVD progression. We aimed to recruit 400 patients with clinically-evident lacunar ischaemic stroke and randomised to cilostazol, isosorbide mononitrate, both or neither, in addition to guideline secondary ischaemic stroke prevention, in a partial factorial design. The primary outcome is feasibility of recruitment and adherence to medication; key secondary outcomes include: drug tolerability; recurrent vascular events, cognition and function at one year after randomisation; and safety (bleeding, falls, death). Data are number (%), and median [interquartile range]. Results The trial commenced on 5 th of February 2018 and ceased recruitment on 31 st of May 2021 with 363 patients randomised, with the following baseline characteristics: average age 64 [56.0, 72.0] years, female 112 (30.9%), stroke onset to randomisation 79.0 [27.0, 244.0] days, hypertension 267 (73.6%), median blood pressures 143.0 [130.0, 157.0]/83.0 [75.0, 90.0] mmHg, current smokers 67 (18.5%), educationally achieved end of school examinations (A-level) or higher 118 (32.5%), modified Rankin scale 1.0 [0.0, 1.0], National Institutes Health stroke scale (NIHSS) 1.0 (1.4), Montreal Cognitive Assessment 26.0 [23.0, 28.0] and total SVD score on brain imaging 1.0 [0.0, 2.0]. This publication summarises the baseline data and presents the statistical analysis plan. Summary The trial is currently in follow-up which will complete on 31 May 2022 with results expected in October 2022.