Statistical Analysis Plan for the Indian Trial of Tranexamic Acid in Spontaneous Intracerebral Hemorrhage Trial

Background Spontaneous intracerebral hemorrhage (sICH) is associated with high mortality and morbidity. Tranexamic acid (TXA) has been used in trauma patients and was associated with improved outcomes, but its efficacy in intracerebral hemorrhage (ICH) remains uncertain. The Indian Trial of Tranexamic Acid in Spontaneous Intracerebral Hemorrhage (INTRINSIC) aims to assess whether TXA improves outcome in adults with sICH. The objective is to formulate a statistical analysis plan (SAP) for INTRINSIC before unblinding data. Methods SAP was developed by trial statisticians with the principal investigator and INTRINSIC team, guided by outcome measures and baseline variables, with all collected data undergoing thorough review. Results Primary outcome, 30-day mortality, will be analyzed in the intention-to-treat as well as per-protocol using unadjusted and adjusted analyses controlling for age, sex, hematoma volume (HV), Glasgow Coma Scale, and intraventricular hemorrhage, with results reported as risk ratios (RRs) and risk differences (RDs) with 95% confidence intervals. Secondary outcomes, including 90-day modified Rankin Scale (mRS), EuroQol-5 Dimension (EQ-5D), HV change, and National Institutes of Health Stroke Scale (NIHSS) at day 7/discharge, will be analyzed using proportional odds regression (ordinal mRS), RR/RD analyses (dichotomized mRS), and linear regression (continuous outcomes), reported as ordinal odds ratios or mean differences, as appropriate. Time-to-event outcomes will use Cox regression and be reported as hazard ratios. Prespecified subgroup analyses will use treatment-by-subgroup interaction models, with subgroup-specific RRs and RDs reported. Conclusions SAP for the INTRINSIC Trial provides a transparent and prespecified framework for trial analyses, enhancing methodological rigor, minimizing bias, and ensuring reproducible results.