Second Enhanced Control of Hypertension and Thrombectomy Stroke Study (ENCHANTED2)

Objectives: To determine the effectiveness of more intensive BP lowering target (\<120 mmHg) compared to higher BP management target (140-180mmHg) on functional outcome in patients with successful recanalization post-MT for AIS due to large vessel occlusion (LVO). Inclusion Criteria: 1. Age ≥18 years; 2. Diagnosis of AIS with LVO confirmed by brain imaging; 3. To receive MT \<24 hours after AIS onset according to local guidelines; 4. Successful recanalization (TICI score ≥2b) after MT; 5. Sustained systolic BP ≥140 mmHg (defined as 2 successive readings \<10 mins) within 3 hours after recanalization; 6. Provide written informed consent (or approved surrogate). Exclusion Criteria: 1. Unlikely to potentially benefit from therapy (e.g. advanced dementia) or very high likelihood of death within 24 hours post-MT, judged by responsible treating clinician; 2. Other medical illness that interferes with outcome assessments and follow-up (e.g. known significant pre-stroke disability (mRS scores 3-5), advance cancer and renal failure); 3. Definite indication/contraindication to different intensities of BP lowering treatment; 4. Specific contraindications to any of the BP agents to be used (eg, patients who are hypersensitive (allergic) to any of the ingredients); 5. Patients with aortic isthmus stenosis and arteriovenous shunt (exception: patients with haemodynamically inactive dialysis shunt); 6. Women who are lactating; 7. Currently participating in another trial which would interfere with outcome assessments. Outcome Measures Primary outcome: functional recovery, defined as a shift (improvement) in scores on the modified Rankin scale (mRS) at 90 days. Secondary outcomes: any intracranial haemorrhage (ICH), symptomatic intracerebral haemorrhage (sICH), early neurological deterioration, imaging assessment (e.g. infarct size, edema volume), death, disability, HRQoL, duration of hospitalization, residence; and health service use for calculation of resources and costs. Randomisation and intervention: Randomisation is via a central internet-based system, stratified by site, time from symptom onset to recanalization (\<6, ≥6 hours), baseline neurological impairment on the National Institutes for Health Stroke Scale (NIHSS \<17 vs ≥17), to ensure balance in key prognostic factors. Intensive BP lowering group: to commence intravenous BP lowering therapy immediately after randomization, with systolic BP target (\<120 mmHg) achieved within 1 hour, and maintained for at least 72 hours (or hospital discharge if earlier). Control group: to receive guideline-recommended BP control strategy to maintain BP level 140-180 mmHg after MT procedure, but BP lowering treatment given only for BP ≥150 mmHg to achieve target ≥140 mmHg. Substudies: Patients enrolled in main study can also be randomised into 2 substudies according to separate eligibility criteria. Both are pilot studies embedded in main trial to recruit as many patients to inform sample size estimates for a further main study. Substudy #1: Timing of anticoagulation Objective: To determine the effectiveness of early initiation of anticoagulation (at Day 4±2 of stroke onset) compared with late initiation (at Day 12±2) on a composite outcome of recurrent AIS, sICH, systemic embolism and/or death within 90 days in patients with AF-related AIS due to LVO who receive MT. Randomisation (allocation 1:1 ratio) via same system as main study and stratified by site and randomisation of BP intervention. Randomised patients will be allocated to either early group of initiating OAC therapy at Day 4±2 day of stroke onset, or late group of initiating OAC therapy at Day 12±2 of stroke onset. Primary outcome: composite of recurrent AIS, sICH, systemic embolism and/or vascular death within 90 days after randomisation. Substudy #2: Duration of dual antiplatelet therapy (DAPT): Objective: To determine the effectiveness of short duration of DAPT (\<6 weeks) compared with standard duration (3 months or more) on recurrence rate within 12 months in patients with AIS due to large artery atherosclerosis (LAA) who are eligible for DAPT post-MT. Randomisation (allocation 1:1 ratio) will be done via the same system as the main study and stratified by site and randomisation of BP intervention. Randomised patients will be allocated to either short duration group of receiving DAPT (aspirin 100 mg and clopidogrel 75 mg per day) for 6 weeks, or standard duration group receiving DAPT for 3 months. DAPT is started \<48 hours post-randomization, and maintained changed to antiplatelet monotherapy (aspirin or clopidogrel) thereafter. Primary outcome is new stroke event (AIS or ICH) over 12 months.