Third Enhanced Control of Hypertension and Thrombectomy Stroke Study

Several clinical trials have produced variable conclusions regarding the effects of intensive blood pressure (BP) lowering in post-EVT acute ischaemic stroke (AIS) patients. Although two trials indicate harm from very intensive target-based treatment (SBP less than 130 mmHg), the others neutral effects in the SBP range 140-160 mmHg. The ENCHANTED3/MT domain of the ACT-GLOBAL platform trial aims to test different approaches to the treatment of elevated SBP in post-EVT AIS patients to find an optimal BP management strategy. ENCHANTED3/MT will randomize (1:1:1) up to 1,900 patients with SBP greater than equal to 150 mmHg post-EVT to conservative (no or minimal SBP reduction by 5-10mmHg or a target of 175-180mmHg if very-high baseline SBP [greater than equal to 180mmHg]), moderate (SBP reduction by 10-20mmHg or a target of 160 ± 5, whichever is higher; no control if low-high baseline SBP [150-160mmHg]), or intensive (SBP reduction by 30-50mmHg or a target of 140±5 mmHg, whichever is higher) BP management.

As usual, hospital care during the study period, BP will be closely assessed up to day 4 to check adherence to the BP management protocol. The BP assessment frequency will be every 15 minutes for the first hour from domain randomisation, hourly from 1 hour to 8 hours, 4 hourly from 8 hours to 24 hours, and daily from Day 2 to Day 4. NIHSS will be conducted at baseline before randomisation into this domain. Randomisation will be stratified by country/region, and eTICI scores after EVT (less than or equal to 2b vs greater than or equal to 2c), using permuted blocks of varying sizes. Response Adaptive Randomisation (RAR) is not applicable in this domain. Randomisation will be centralized, secure, and concealed, using a web-based server, thus eliminating the possibility of imbalance in baseline prognostic variables and confounding by allocation bias. Investigators will rapidly access the randomiser using a web browser/application accessible using a username and password secured via multi-factor authentication. Primary outcome is modified Rankin scale (mRS) at 90 days analysed with utility-weighted mRS using a Bayesian hierarchical linear model. Adaptive analyses will be conducted 3-monthly with prespecified statistical triggers for superiority, inferiority and equivalence.