계명대학교 의학도서관 Repository

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial

Metadata Downloads
Author(s)
Michael D Hill ProfMayank GoyalBijoy K MenonRaul G Nogueira ProfRyan A McTaggartAndrew M Demchuk ProfAlexandre Y PoppeBrian H BuckThalia S FieldDar DowlatshahiBrian A van AdelRichard H SwartzRuchir A ShahEric SauvageauCharlotte ZernaJohanna M OspelManish JoshiMohammed A AlmekhlafiKarla J RyckborstMark W LowerisonKathy HeardDavid GarmanDiogo HaussenShawna M CuttingShelagh B Coutts ProfDaniel Roy ProfJeremy L RempelAxel CR RohrDaniela Iancu MScDemetrios J SahlasAmy Y X YuThomas G DevlinRicardo A HanelVolker PuetzFrank L Silver ProfBruce C V CampbellRené ChapotJeanne TeitelbaumJennifer L MandziaTimothy J KleinigDavid Turkel-ParrellaDonald HeckMichael E Kelly ProfAditya BharathaOh Young Bang ProfAshutosh JadhavRishi GuptaDonald F FreiJason W TarpleyCameron G McDougall ProfStaffan Holmin ProfJoung-Ho Rha ProfAjit S PuriMarie-Christine CaenGötz Thomalla ProfHana ChoeStephen J Phillips ProfJoseph L SchindlerJohn ThorntonSimon NagelJi Hoe Heo ProfSung-Il Sohn ProfMarios-Nikos Psychogios ProfRonald F BudzikSidney Starkman ProfColeman O MartinPaul A BurnsSeán MurphyGeorge A LopezJoey EnglishMichael Tymianski Prof
Keimyung Author(s)
Sohn, Sung Il
Department
Dept. of Neurology (신경과학)
Journal Title
Lancet
Issued Date
2020
Volume
395
Issue
10227
Abstract
Background:
Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke.

Methods:
For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1: 1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018.

Findings:
Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups.

Interpretation:
Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo.

Funding:
Canadian Institutes for Health Research, Alberta Innovates, and NoNO.
Keimyung Author(s)(Kor)
손성일
Publisher
School of Medicine (의과대학)
Citation
Michael D Hill Prof et al. (2020). Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial. Lancet, 395(10227), 878–887. doi: 10.1016/S0140-6736(20)30258-0
Type
Article
ISSN
1474-547X
Source
https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0140673620302580
DOI
10.1016/S0140-6736(20)30258-0
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43230
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Neurology (신경과학)
공개 및 라이선스
  • 공개 구분공개
  • 엠바고Forever
파일 목록

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.