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.

Keywords

Acute ischemic stroke hypertension blood pressure lowering mechanical thrombectomy thrombolysis clinical trial outcomes

Get full access to this article

View all access options for this article.

References

Goyal

Menon

Van Zwam

, et al Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016; 387: 1723–1731.

Rabinstein

Albers

Brinjikji

Koch

Factors that may contribute to poor outcome despite good reperfusion after acute endovascular stroke therapy. Int J Stroke 2019; 14: 23–31.

Mulder

MJHL

Ergezen

Lingsma

, et al Baseline blood pressure effect on the benefit and safety of intra-arterial treatment in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). Stroke 2017; 48: 1869–1876.

Mistry

Nakawah

, et al Systolic blood pressure within 24 hours after thrombectomy for acute ischemic stroke correlates with outcome. J Am Heart Assoc 2017; 6: e006167.

Goyal

Tsivgoulis

Pandhi

, et al Blood pressure levels post mechanical thrombectomy and outcomes in large vessel occlusion strokes. Neurology 2017; 89: 540–547.

Anadani

Orabi

Alawieh

Goyal

Alexandrov

Petersen

, et al Blood pressure and outcome after mechanical thrombectomy with successful revascularization. Stroke 2019; 50: 2448–2454.

Anderson

Huang

Lindley

, et al Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial. Lancet 2019; 393: 877–888.

Martins

Sargento-Freitas

Silva

Jesus-Ribeiro

Correia

Gomes

, et al Recanalization modulates association between blood pressure and functional outcome in acute ischemic stroke. Stroke 2016; 47: 1571–1576.

Matusevicius

Cooray

Bottai

, et al Blood pressure after endovascular thrombectomy: modeling for outcomes based on recanalization status. Stroke 2020; 51: 519–525.

10.

Powers

Rabinstein

Ackerson

, et al Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2019; 50: e344–e418.

11.

Mistry

Mayer

Khatri

Blood pressure management after mechanical thrombectomy for acute ischemic stroke: a survey of the StrokeNet sites. J Stroke Cerebrovasc Dis 2018; 27: 2474–2478.

12.

Mazighi

Richard

Lapergue

Sibon

Gory

Berge

, et al Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial. Lancet Neurol 2021; 20: 265–274.

13.

von Kummer

Broderick

Campbell

Demchuk

Goyal

Hill

, et al The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke 2015; 46: 2981–2986.