Mediation Analysis to Identify Individual Component Effects of the Care Bundle to Improve Functional Outcome After ICH in the INTERACT3 Study

作者：Xinwen Ren, Qiang Li, Menglu Ouyang, Laurent Billot, Xiaoying Chen, Paula Muñoz Venturelli, Asita de Silva, Thang Huy Nguyen, Kolawole Wahab, Jeyaraj Pandian, Mohammad Wasay, Octávio Marques Pontes‐Neto, Carlos Abanto, Antonio Araúz, Chao You, Lu Ma, Xin Hu, Craig S. Anderson, Xia Wang, Lili Song, as the INTERACT3 Investigators · 发表于：Neurology · 年份：2025 · DOI：10.1212/wnl.0000000000214070 · 被引用次数：6 · 研究领域：Intracerebral and Subarachnoid Hemorrhage Research、Acute Ischemic Stroke Management、Traumatic Brain Injury and Neurovascular Disturbances

BACKGROUND AND OBJECTIVES: The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3) showed that the implementation of a care bundle improves the functional outcome of patients who experience acute intracerebral hemorrhage (ICH). However, uncertainty exists over the relative contribution of each component of the care bundle for the benefit. METHODS: INTERACT3 used a stepped-wedge, cluster randomized controlled trial design, which was conducted in 5 lower and 4 upper middle-income countries and 1 high-income country. Compared with usual care, there was a statistically significant beneficial effect of the intervention, a care bundle comprising early control of elevated blood pressure (BP), glucose, and temperature and reversal of warfarin-related anticoagulation, on the primary outcome of functional recovery of ICH. We performed a model-based causal mediation analysis to assess the contribution of each component of the care bundle to the overall effect, as measured by the modified Rankin Scale (mRS) at 6 months after randomization. The mediation analysis considered whether protocol-specified treatment targets were reached as well as the actual achieved levels of physiologic control according to the summary measures of systolic BP (mean, variation over 1-24 hours, and reduction in 1 hour) and mean of blood glucose, body temperature, and international normalized ratio over 24 hours. The analyses were performed in the modified int...