Supplementary Material for: Statistical Analysis Plan for the INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4).

Introduction: Recruitment is complete in the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4) is a multicenter, prospective, randomized, open-label, blinded endpoint assessed trial of pre-hospital blood pressure (BP) lowering initiated in the ambulance for patients with a suspected acute stroke and elevated BP in China. According to the registered and published trial protocol and developed by the blinded trial Steering Committee and Operations team, this manuscript outlines a detailed statistical analysis plan for the trial prior to database lock.
Methods: Patients were randomized (1:1) to intensive (target systolic BP [SBP] 130-140 mmHg within 30 minutes) or guideline-recommended BP management (BP lowering only considered if SBP >220 mmHg) group. Primary outcome is an ordinal analysis of the full range of scores on the modified Rankin scale at 90 days. A modified sample size of 2320 was estimated to provide 90% power to detect a 22% reduction in the odds (common odds ratio of 0.78) of a worse functional outcome using ordinal logistic regression, on the assumption of 5% patients with missing outcome and 6% patients with a stroke mimic.
Conclusion: The statistical analysis plan for the trial has been developed to ensure transparent, verifiable, and prespecified analysis, and to avoid potential bias in the evaluation of the trial intervention.

引言：第四项急性超早期卒中救护车降压治疗试验（INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial, INTERACT4）的招募工作已完成。该试验是一项在中国开展的多中心、前瞻性、随机、开放标签、盲法终点评估试验，针对疑似急性卒中且血压（blood pressure, BP）升高的患者，在救护车中启动院前降压干预。本手稿依据已注册并发表的试验方案，由盲法试验指导委员会与运营团队制定，旨在详述数据库锁定前该试验的详细统计分析计划。
方法：患者按1:1比例随机分为强化降压组（目标为30分钟内将收缩压（systolic blood pressure, SBP）控制在130~140 mmHg）或指南推荐的血压管理组（仅当收缩压＞220 mmHg时考虑降压）。主要结局为90天时改良Rankin量表（modified Rankin scale, mRS）全范围评分的有序分析。经调整后的样本量为2320例，假设5%的患者存在结局数据缺失、6%的患者为卒中模拟病，采用有序logistic回归分析，可获得90%的检验效能以检测功能结局恶化的比值比降低22%（通用比值比为0.78）。
结论：本试验的统计分析计划旨在确保分析过程透明、可验证且为预先设定，并避免试验干预措施评估中出现潜在偏倚。