Nerinetide不能改善血管内血栓切除术患者预后
2020-02-25   阅读:607   来源:柳叶刀

加拿大卡尔加里大学山麓医疗中心Michael D Hill课题组的一项最新研究,分析了Nerinetide治疗急性缺血性中风的的疗效和安全性。2020年2月20日出版的《柳叶刀》发表了这项成果。

Nerinetide是干扰突触后密度蛋白-95的一种二十碳肽,是一种神经保护剂,在临床前缺血再灌注的中风模型中有效。研究组评估了Nerinetide治疗急性缺血性中风患者行快速血管内血栓切除术中缺血再灌注的疗效和安全性。

研究组在8个国家/地区的48家急诊医院进行了一项多中心、双盲、随机、安慰剂对照研究。2017年3月1日至2019年8月12日,研究组招募了1105名因大血管闭塞而在12小时治疗窗口内出现急性缺血性中风的患者,年龄均大于18岁,Alberta卒中项目早期CT评分(ASPECTS)大于4分,CT血管造影显示侧支中度或良好充盈。

将患者按1:1随机分组,其中549例接受Nerinetide静脉注射,556例接受生理盐水安慰剂。治疗90天后,Nerinetide组中有337名患者(61.4%)改良Rankin量表(mRS)评分为0-2,而安慰剂组中有329名(59.2%),差异不显著。两组间的次要指标差异亦不大。Nerinetide抑制了阿替普酶的治疗效果。两组间严重不良事件的发生率相似。

总之,与安慰剂相比,Nerinetide并不能改善血管内血栓切除术患者的预后。

附:英文原文

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

Author: Michael D Hill, Mayank Goyal, Bijoy K Menon, Raul G Nogueira, Ryan A McTaggart, Andrew M Demchuk, Alexandre Y Poppe, Brian H Buck, Thalia S Field, Dar Dowlatshahi, Brian A van Adel, Richard H Swartz, Ruchir A Shah, Eric Sauvageau, Charlotte Zerna, Johanna M Ospel, Manish Joshi, Mohammed A Almekhlafi, Karla J Ryckborst, Mark W Lowerison, Kathy Heard, David Garman, Diogo Haussen, Shawna M Cutting, Shelagh B Coutts, Daniel Roy, Jeremy L Rempel, Axel CR Rohr, Daniela Iancu, Demetrios J Sahlas, Amy Y X Yu, Thomas G Devlin, Ricardo A Hanel, Volker Puetz, Frank L Silver, Bruce C V Campbell, René Chapot, Jeanne Teitelbaum, Jennifer L Mandzia, Timothy J Kleinig, David Turkel-Parrella, Donald Heck, Michael E Kelly, Aditya Bharatha, Oh Young Bang, Ashutosh Jadhav, Rishi Gupta, Donald F Frei, Jason W Tarpley, Cameron G McDougall, Staffan Holmin, Joung-Ho Rha, Ajit S Puri, Marie-Christine Camden, Gtz Thomalla, Hana Choe, Stephen J Phillips, Joseph L Schindler, John Thornton, Simon Nagel, Ji Hoe Heo, Sung-Il Sohn, Marios-Nikos Psychogios, Ronald F Budzik, Sidney Starkman, Coleman O Martin, Paul A Burns, Seán Murphy, George A Lopez, Joey English, Michael Tymianski, Andrew Demchuk, Philip Barber, Eric Smith, Simerpreet Bal, Suresh Subramaniam, Steven Peters

Issue&Volume: 2020-02-20

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.

DOI: 10.1016/S0140-6736(20)30258-0

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