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

Lili Song; Pengfei Yang; Yongwei Zhang; Xiaoxi Zhang; Xiaoying Chen; Yunke Li; Hongjian Shen; Lei Zhang; Zifu Li; Yongxin Zhang; Pengfei Xing; Ping Zhang; Yihan Zhou; Xinwen Ren; Laurent Billot; Xia Wang; Mark W Parsons; Ken Butcher; Bruce Campbell; Thompson Robinson; Mayank Goyal; Diederik Dippel; Yvo Roos; Charles Majoie; Jianmin Liu; Craig S Anderson; for ENCHANTED-MT Investigators

doi:10.1177/17474930221120345

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

Int J Stroke. 2023 Mar;18(3):364-369. doi: 10.1177/17474930221120345. Epub 2022 Aug 24.

Authors

Lili Song^{1

2}, Pengfei Yang³, Yongwei Zhang³, Xiaoxi Zhang³, Xiaoying Chen^{1

2}, Yunke Li¹, Hongjian Shen³, Lei Zhang³, Zifu Li³, Yongxin Zhang³, Pengfei Xing³, Ping Zhang³, Yihan Zhou³, Xinwen Ren¹, Laurent Billot², Xia Wang², Mark W Parsons⁴, Ken Butcher⁵, Bruce Campbell⁶, Thompson Robinson⁷, Mayank Goyal⁸, Diederik Dippel⁹, Yvo Roos¹⁰, Charles Majoie¹¹, Jianmin Liu³, Craig S Anderson^{1

2

12}; for ENCHANTED-MT Investigators

Affiliations

¹ The George Institute for Global Health China, Beijing, China.
² The George Institute for Global Health, Faculty of Medicine, The University of New South Wales (UNSW), Sydney, NSW, Australia.
³ Neurovascular Center, Changhai Hospital, Naval Medical University, Shanghai, China.
⁴ Ingham Institute for Applied Medical Research, Liverpool Hospital, The University of New South Wales (UNSW), Sydney, NSW, Australia.
⁵ Prince of Wales Clinical School, The University of New South Wales (UNSW), Sydney, NSW, Australia.
⁶ Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia.
⁷ Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK.
⁸ Departments of Radiology and Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
⁹ Department of Neurology, Erasmus MC, Rotterdam, The Netherlands.
¹⁰ Department of Neurology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
¹¹ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
¹² Neurology Department, Royal Prince Alfred Hospital, Sydney Health Partners, Sydney, NSW, Australia.

PMID: 35924814
DOI: 10.1177/17474930221120345

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; blood pressure lowering; clinical trial; hypertension; mechanical thrombectomy; outcomes; thrombolysis.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Brain Ischemia* / drug therapy
Humans
Hypertension* / diagnosis
Hypertension* / drug therapy
Ischemic Stroke*
Multicenter Studies as Topic
Prospective Studies
Randomized Controlled Trials as Topic
Stroke* / therapy
Thrombectomy
Treatment Outcome

Associated data

ClinicalTrials.gov/NCT04140110