Statistical Analysis Plan for the Optimal Post rTpa-Iv Monitoring in Ischemic Stroke Trial (OPTIMIST)

1The OPTIMIST trial aims to determine whether low-intensity monitoring is at least as effective ("non-inferior") to standard monitoring, on the functional recovery of patients who have received recombinant tissue plasminogen activator or equivalent lytic reperfusion treatment for acute ischaemic stroke. It is designed as an international, multicenter, stepped-wedge (4 periods/3 steps) cluster randomized trial. This statistical analysis plan pre-specifies the method of analysis for every outcome and key variable collected in the trial. The primary outcome is an "unfavourable outcome" at Day 90, defined as a score of 2 to 6 on the modified Rankin scale. The primary analysis will consist in a log-binomial regression adjusted for the effect of time and for clustering by site using a random effect. The non-inferiority margin was pre-specified as a relative risk of 1.15 for a bad outcome; thus, non-inferiority will be declared if the upper bound of the 95% confidence interval around the relative risk is lower than 1.15. The primary analysis will adjust for calendar time (6-month intervals) and will be based on imputed data. The analysis plan also includes planned sensitivity analyses including covariate adjustments and subgroup analyses. 2 Administrative information2.1 Study identifiersO_LIProtocol Number: GI-AU-NMH-2019-CA Version: 3.0, Date: 3 March 2021 C_LIO_LIClinicalTrials.gov register Identifier: NCT03734640 C_LIO_LIAustralian New Zealand Clinical Trial Registry: ACTRN 12619001556134 C_LI 2.2 Revision history O_TBL View this table: org.highwire.dtl.DTLVardef@27d512org.highwire.dtl.DTLVardef@115cc51org.highwire.dtl.DTLVardef@190ca9org.highwire.dtl.DTLVardef@8e41ddorg.highwire.dtl.DTLVardef@18624dd_HPS_FORMAT_FIGEXP M_TBL C_TBL 2.3 Contributors to the statistical analysis planLB - Main author; developed the initial draft and prepared subsequent versions. SB - Prepared initial draft and reviewed subsequent versions. MO, CA - Reviewed every draft and approved final version. LX - Prepared economic analysis section and approved final version. SJ - Comments on economic analysis plan; approved final draft. XW, AM, BJ, DS, PK, PM-V, DD, YS, LS, WAWZ, NHT, CD, TR, RIL - Approved final draft.