已入深夜,您辛苦了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!祝你早点完成任务,早点休息,好梦!

Safety and efficacy of platelet glycoprotein VI inhibition in acute ischaemic stroke (ACTIMIS): a randomised, double-blind, placebo-controlled, phase 1b/2a trial

医学 安慰剂 冲程(发动机) 双盲 缺血性中风 血小板 内科学 物理医学与康复 物理疗法 缺血 病理 物理 热力学 替代医学
作者
Mikaël Mazighi,Martin Köhrmann,Robin Lemmens,Philippe Lyrer,Carlos A. Molina,Sébastien Richard,Danilo Toni,Yannick Plétan,Anouar Sari,Adeline Meilhoc,Martine Jandrot‐Perrus,Sophie Binay,Gilles Avenard,Andrea Comenducci,Jean‐Marie Grouin,James C. Grotta,Jean François Albucher,Angelika Alonso,Jörg Berrouschot,Charlotte Cordonnier,Sylvie De Raedt,Philippe Desfontaines,Émilie Doche,Dimitri Hemelsoet,Francisco Macian-Montoro,Jaime Masjuán,Michaël Obadia,André Peeters,Johann Pelz,Peggy Reiner,Tomás Segura,Joaquı́n Serena,Igor Sibon,José Ignacio Tembl,Stéphane Vannier,Mathieu Zuber
出处
期刊:Lancet Neurology [Elsevier]
卷期号:23 (2): 157-167 被引量:16
标识
DOI:10.1016/s1474-4422(23)00427-1
摘要

Summary

Background

Antagonists of glycoprotein VI-triggered platelet activation used in combination with recanalisation therapies are a promising therapeutic approach in acute ischaemic stroke. Glenzocimab is an antibody fragment that inhibits the action of platelet glycoprotein VI. We aimed to determine and assess the safety and efficacy of the optimal dose of glenzocimab in patients with acute ischaemic stroke eligible to receive alteplase with or without mechanical thrombectomy.

Methods

This randomised, double-blind, placebo-controlled study with dose-escalation (1b) and dose-confirmation (2a) phases (ACTIMIS) was done in 26 stroke centres in six European countries. Participants were adults (≥18 years) with disabling acute ischaemic stroke with a National Institutes of Health Stroke Scale score of 6 or higher before alteplase administration. Patients were randomly assigned treatment using a central electronic procedure. Total administered dose at the end of the intravenous administration was 125 mg, 250 mg, 500 mg, and 1000 mg of glenzocimab or placebo in phase 1b and 1000 mg of glenzocimab or placebo in phase 2a. Treatment was initiated 4·5 h or earlier from stroke symptom onset in patients treated with alteplase with or without mechanical thrombectomy. The sponsor, study investigator and study staff, patients, and central laboratories were all masked to study treatment until database lock. Primary endpoints across both phases were safety, mortality, and intracranial haemorrhage (symptomatic, total, and fatal), assessed in all patients who received at least a partial dose of study medication (safety set). The trial is registered on ClinicalTrials.gov, NCT03803007, and is complete.

Findings

Between March 6, 2019, and June 27, 2021, 60 recruited patients were randomly assigned to 125 mg, 250 mg, 500 mg, or 1000 mg glenzocimab, or to placebo in phase 1b (n=12 per group) and were included in the safety analysis. Glenzocimab 1000 mg was well tolerated and selected as the phase 2a recommended dose; from Oct 2, 2020, to June 27, 2021, 106 patients were randomly assigned to glenzocimab 1000 mg (n=53) or placebo (n=53). One patient in the placebo group received glenzocimab in error and therefore 54 and 52, respectively, were included in the safety set. In phase 2a, the most frequent treatment-emergent adverse event was non-symptomatic haemorrhagic transformation, which occurred in 17 (31%) of 54 patients treated with glenzocimab and 26 (50%) of 52 patients treated with placebo. Symptomatic intracranial haemorrhage occurred in no patients treated with glenzocimab compared with five (10%) patients in the placebo group. All-cause deaths were lower with glenzocimab 1000 mg (four [7%] patients) than with placebo (11 [21%] patients).

Interpretation

Glenzocimab 1000 mg in addition to alteplase, with or without mechanical thrombectomy, was well tolerated, and might reduce serious adverse events, intracranial haemorrhage, and mortality. These findings support the need for future research into the potential therapeutic inhibition of glycoprotein VI with glenzocimab plus alteplase in patients with acute ischaemic stroke.

Funding

Acticor Biotech.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
3秒前
4秒前
5秒前
nesta627发布了新的文献求助10
6秒前
不爱说话发布了新的文献求助10
6秒前
7t1n9发布了新的文献求助10
7秒前
7秒前
Abmony发布了新的文献求助20
7秒前
8秒前
GXY完成签到,获得积分10
8秒前
10秒前
10秒前
Tong应助小周碎碎念采纳,获得10
10秒前
外向春天完成签到 ,获得积分10
11秒前
LD完成签到 ,获得积分10
11秒前
Eourique发布了新的文献求助10
12秒前
pathway完成签到,获得积分10
15秒前
liuliu发布了新的文献求助10
16秒前
16秒前
17秒前
无心的海蓝完成签到,获得积分10
17秒前
18秒前
Lucas应助schinco采纳,获得10
19秒前
科研通AI2S应助yhyhyhyh采纳,获得10
19秒前
开心歌曲关注了科研通微信公众号
19秒前
19秒前
怕黑的老九完成签到,获得积分10
19秒前
caimiemie发布了新的文献求助10
22秒前
林文静发布了新的文献求助10
24秒前
xij关闭了xij文献求助
27秒前
颜缭完成签到,获得积分10
29秒前
隐形曼青应助科研通管家采纳,获得10
30秒前
桐桐应助科研通管家采纳,获得10
30秒前
Thanatos应助科研通管家采纳,获得10
30秒前
Singularity应助科研通管家采纳,获得10
30秒前
无花果应助科研通管家采纳,获得10
30秒前
空心菜公主oo完成签到,获得积分10
30秒前
oceanao应助科研通管家采纳,获得10
30秒前
传奇3应助科研通管家采纳,获得10
30秒前
30秒前
高分求助中
Becoming: An Introduction to Jung's Concept of Individuation 600
Ore genesis in the Zambian Copperbelt with particular reference to the northern sector of the Chambishi basin 500
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 500
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 500
Die Gottesanbeterin: Mantis religiosa: 656 400
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 400
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3164662
求助须知:如何正确求助?哪些是违规求助? 2815496
关于积分的说明 7909685
捐赠科研通 2475233
什么是DOI,文献DOI怎么找? 1317952
科研通“疑难数据库(出版商)”最低求助积分说明 631984
版权声明 602282