Statistical Analysis
SE, ICH, death, hematoma
REGRESSION, EVENTS, SECONDARY, HEMATOMA
The sample size for TICH-NOAC was calculated at 109 participants to be able to detect a significant relative difference of 50% in the rate of HE (27% in the treatment versus 54% in the control arm) with a 5% dropout rate and 80% power at a 2-sided α of 5%. The control group HE rate was based on data from vitamin K antagonist–associated ICH,We evaluated the interrater reliability of the primary outcome assessment using the κ statistic (with a value of 0 indicating chance agreement and 1 perfect agreement, while values of 0.61–0.80 and over 0.80 indicate substantial and near perfect agreement, respectively). Following the prespecified statistical plan and in accordance with prior research,In secondary analyses, we compared the secondary binary outcomes symptomatic HE, dichotomized mRS, and death between the treatment groups using binary logistic regression adjusted for baseline hematoma volume. The remaining binary secondary outcomes were compared using unadjusted Firth regression as appropriate, depending on the small number of outcome events. We additionally analyzed 90-day mRS over its entire ordinal range using shift analysis adjusted for baseline hematoma volume, assessing the validity of the proportional odds assumption with visual inspection of the mRS distribution and using both the approximate likelihood ratio and Brant test. We compared the absolute hematoma volume change between treatment groups using median regression adjusted for baseline hematoma volume with bootstrapped SE estimation and 1000 repetitions, since the assumptions of linear regression were violated even after log-transformation. Further not prespecified exploratory analyses of additional binary outcomes were done using logistic regression adjusted for baseline hematoma volume.We analyzed the primary outcome in prespecified subgroups using binary logistic regression adjusted for baseline hematoma volume and appropriate interaction terms. We also explored the following not prespecified subgroups: systolic blood pressure on admission (≤170 versus >170 mm Hg), concurrent use of 4fPCC (used versus not used), and ANNEXa-I (ongoing randomized controlled trial investigating andexanet alfa in patients with factor Xa inhibitor–associated ICH; The nominal level of significance for all analyses was a The trial was overseen by a Steering Committee and run by an Executive Committee based at the University Hospital Basel and chaired by P.A.L. An independent data safety monitoring board was planned but was not appointed due to early trial termination. The trial was prospectively registered at 