Enhanced versus standard blood pressure lowering on intracranial aneurysm rupture or growth (ChATIA-1 Trial): Protocol for a multi-centered, prospective, open-label randomized controlled trial

Kaige Zheng^1,2Zheng Wen^1,2Jiangan Li³Zengli Miao⁴Xiaojie Lu⁴Hongwei He^1,2Yong Cao^1,2Bing Zhao⁵Michael R Levitt⁶Lei Chen⁷Shuo Wang^1,2*Chengcheng Zhu⁸Qingyuan Liu^1,2

• ¹Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
• ²China National Clinical Research Center for Neurological Diseases, Beijing, China
• ³Department of Emergency, Jiangnan University Medical Center, Wuxi, China
• ⁴Department of Neurosurgery, Jiangnan University Medical Center, Wuxi, China
• ⁵Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
• ⁶Department of Neurological Surgery, University of Washington, Seattle, United States
• ⁷Department of Neurosurgery, the First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China
• ⁸Department of Radiology, University of Washington, Seattle, China

Background: Hypertension is a common comorbidity in patients with unruptured intracranial aneurysms, which is closely related to the instability of aneurysms. Though anti-hypertension therapy has been recommended by several guidelines, the optimal blood pressure range remains unknown. This trial aims to determine the optimal range of blood pressure by comparing standard blood pressure reduction and intensive blood pressure reduction to reduce the instability of unruptured intracranial aneurysms. Methods/Design: This trial is a multicenter, prospective, open-label, randomized controlled trial with minimization to ensure allocation concealment. 570 patients with unruptured intracranial aneurysms and hypertension will be recruited by 9 centers in China. Patients will be allocated to the standard blood pressure lowering (SBPL) group (systolic blood pressure at 120-140mmHg) or the enhanced blood pressure lowering (EBPL) group (systolic blood pressure at <120mmHg). The primary outcome is aneurysm instability within 24 months after appropriate blood pressure lowering therapy, including aneurysm growth and aneurysm rupture. During follow-up, Blood pressure data will be collected monthly, while radiological examination for aneurysms will be performed at 6±1 months, 12±1 months and 24 ±1 months. The trial has 85% power to reduce 60% of aneurysm instability. Discussion: The China Antihypertensive Trial for Intracranial Aneurysm (ChATIA) trial is a randomized trial about blood pressure lowering therapy for UIA patients. In this study, a new strategy and evidence will be provided for blood pressure management in the future. Trial registration number: clinicaltrials.gov, NCT05941377 Key words: Unruptured intracranial aneurysm; Blood pressure; Aneurysm instability; Rupture; Growth