The second randomized controlled ENhanced Control of Hypertension ANd Thrombectomy strokE stuDy (ENCHANTED2): Protocol and progress

Abstract

Background: Uncertainty exists over the optimal level of blood pressure (BP) after mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Objectives: We aim to determine the effectiveness and safety of intensive BP-lowering following MT reperfusion of large-vessel occlusion (LVO)-related AIS. Design: The second ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED2) is an investigator-initiated, multicenter, prospective, randomized, open, blinded-endpoint (PROBE) trial of intensive systolic BP (SBP) control in reperfused (extended treatment in cerebral infarction (eTICI) classification 2b/2c/3) LVO-AIS patients with persistent hypertension (SBP ⩾ 140 mmHg) at 60+ sites in China, and Australia and the United Kingdom. Eligible patients are centrally randomly allocated to more- (target SBP ⩽ 120 mmHg within 1 h) or less-intensive (target SBP 140–180 mmHg) BP management, to be maintained for 72 h. Primary outcome is an ordinal shift analysis of scores on the modified Rankin scale (mRS) at 90 days. Sample size of 2257 patients provides 90% power to detect a 6.5% absolute reduction in poor outcome from more-intensive BP-lowering using ordinal logistic regression. Progress: Recruitment started in China in July 2020. At a meeting of the independent Data and Safety Monitoring Board in March 2022 to review primary outcome data available for 347 patients, they recommended suspension of recruitment due to safety concerns in the more-intensive group; which was implemented by the Trial Steering Committee (TSC) with 817 randomized patients only in China. The TSC then stopped recruitment after the safety concerns persisted on further review of the data in June 2022. The TSC will make a decision on restarting the trial with modification of the protocol when the results are made public. Discussion: ENCHANTED2 will provide further randomized evidence on the role of intensive BP-lowering after reperfusion in MT-treated AIS patients. Trial registration: ClinicalTrials.gov NCT04140110; registered 25 October 2019.