Clinical trial NCT06352619: Third Enhanced Control of Hypertension and Thrombectomy Stroke Domain Within ACT-GLOBAL Adaptive Platform Trial
Official title: Third Enhanced Control of Hypertension and Thrombectomy Stroke Domain Within A Multi-faCtorial, mulTi-arm, Multi-staGe, Randomised, gLOBal Adaptive pLatform Trial for Stroke (ACT-GLOBAL_ENCHANTED3/MT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ischemic Stroke, Acute
Keywords: Blood Pressure
Endovascular Therapy
Ischemic Stroke
Lead sponsor: The George Institute
Sponsor class: OTHER
Collaborators: name: University of Calgary
name: Changhai Hospital
First posted: 2024-04-08
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 \<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 2,000 patients with SBP ≥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 \[≥180mmHg\]), 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.

Detailed description: ACT-GLOBAL is an international, multi-factorial, multi-arm, multi-stage, randomized, adaptive platform trial designed to simultaneously evaluate multiple treatments that may improve outcomes in stroke. One domain is ENCHANTED3/MT aiming to compare three BP lowering management strategies in post-EVT AIS patients with elevated SBP determine the best approach to improve functional outcome.

Background and Rationale - Different reperfusion status may have different BP patterns. A U-shaped correlation between post-EVT BP and outcomes may exist for patients who underwent recanalisation post-EVT. In addition, different BP lowering strategy may have different safety profiles and may potentially impact differently with regards to the risk of ICH for patients with reperfusion therapy.

The controversial overall clinical effect seen in clinical trials, including ENCHANTED2/MT, OPTIMAL BP, BP TARGET, BEST II and ENCHANTED, does not resolve the question over the optimal BP control strategy following EVT. The evidence is insufficient to make sensible recommendations over the optimal BP management in this important clinical group. Thus, the Blood Pressure Domain (ENCHANTED3/MT) aims to test different treatment approaches to the control of elevated SBP post-EVT in AIS patients to find the optimal BP management that leads to improved functional status with reduced ICH and no other harms.

ENCHANTED3/MT will randomize (1:1:1) up to 2,000 patients with SBP ≥150 mmHg post-EVT to the following three BP lowering management strategies.

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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years;
2. Use of endovascular therapy (EVT) within 24 hours of symptom onset or last known well according to local guidelines;
3. Sustained high systolic blood pressure ≥150 mmHg (2 readings \<10 mins apart) within 3 hours after completion of EVT.

Exclusion Criteria:

1.Any definite contraindications to BP lowering treatment.

Primary outcomes:
measure: modified Rankin scale
timeFrame: 90 days
Secondary outcomes:
measure: Excellent functional neurological outcome
timeFrame: 90 days
measure: Independent functional neurological outcome
timeFrame: 90 days
measure: Health Related Quality of Life
timeFrame: 90 days
measure: Mortality
timeFrame: 90 days
measure: Ordinal shift of 7 levels of modified Rankin scale
timeFrame: 90 days
measure: National Institute of Health Stroke Scale (NIHSS) score
timeFrame: 24-48 hours
measure: Any intracranial haemorrhage (ICH)
timeFrame: 2 days
measure: Symptomatic intracerebral haemorrhage (sICH)
timeFrame: 2 days
measure: Serious Adverse Event (SAE)
timeFrame: 4 days
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: The George Institute for Global Health
state: New South Wales
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: The George Institute
name: Craig Anderson, PhD
role: PRINCIPAL_INVESTIGATOR
References: