蛛网膜下腔出血后 SFX-01 随机对照试验 - SAS 研究。

IF 3.8 2区 医学 Q1 CLINICAL NEUROLOGY
Ardalan Zolnourian, Patrick Garland, Patrick Holton, Mukul Arora, Jonathan Rhodes, Christopher Uff, Tony Birch, David Howat, Stephen Franklin, Ian Galea, Diederik Bulters
{"title":"蛛网膜下腔出血后 SFX-01 随机对照试验 - SAS 研究。","authors":"Ardalan Zolnourian, Patrick Garland, Patrick Holton, Mukul Arora, Jonathan Rhodes, Christopher Uff, Tony Birch, David Howat, Stephen Franklin, Ian Galea, Diederik Bulters","doi":"10.1007/s12975-024-01278-1","DOIUrl":null,"url":null,"abstract":"<p><p>SFX-01 is a novel drug for clinical delivery of sulforaphane (SFN). SFN is a potent nuclear factor erythroid 2-related factor 2 activator that reduces inflammation and oxidation, improving outcomes after subarachnoid haemorrhage (SAH) in animal models. This was a multi-centre, double-blind, placebo-controlled, parallel-group randomised clinical trial to evaluate the safety, pharmacokinetics and efficacy of 28 days of SFX-01 300 mg BD in patients aged 18-80 with spontaneous SAH and high blood load on CT. Primary outcomes were (1) safety, (2) plasma and CSF SFN and metabolite levels and (3) vasospasm on transcranial doppler ultrasound. Secondary outcomes included CSF haptoglobin and malondialdehyde and clinical outcome on the modified Rankin Scale (mRS) and SAH outcome tool (SAHOT). A total of 105 patients were randomised (54 SFX-01, 51 placebo). There were no differences in adverse events other than nausea (9 SFX-01 (16.7%), 1 placebo (2.0%)). SFN, SFN-glutathione and SFN-N-acetyl-cysteine AUC<sub>last</sub> were 16.2, 277 and 415 h × ng/ml. Plasma SFN was higher in GSTT1 null individuals (t = 2.40, p = 0.023). CSF levels were low with many samples below the lower limit of quantification and predicted by the CSF/serum albumin ratio (R<sup>2</sup> = 0.182, p = 0.039). There was no difference in CSF haptoglobin (1.981 95%CI 0.992-3.786, p = 0.052) or malondialdehyde (1.12 95%CI 0.7477-1.687, p = 0.572) or middle cerebral artery flow velocity (1.04 95%CI 0.903-1.211, p = 0.545) or functional outcome (mRS 1.647 95%CI 0.721-3.821, p = 0.237, SAHOT 1.082 95%CI 0.464-2.525, p = 0.855). SFX-01 is safe and effective for the delivery of SFN in acutely unwell patients. SFN penetrated CSF less than expected and did not reduce large vessel vasospasm or improve outcome. Trial registration: NCT02614742 clinicaltrials.gov.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Randomised Controlled Trial of SFX-01 After Subarachnoid Haemorrhage - The SAS Study.\",\"authors\":\"Ardalan Zolnourian, Patrick Garland, Patrick Holton, Mukul Arora, Jonathan Rhodes, Christopher Uff, Tony Birch, David Howat, Stephen Franklin, Ian Galea, Diederik Bulters\",\"doi\":\"10.1007/s12975-024-01278-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>SFX-01 is a novel drug for clinical delivery of sulforaphane (SFN). SFN is a potent nuclear factor erythroid 2-related factor 2 activator that reduces inflammation and oxidation, improving outcomes after subarachnoid haemorrhage (SAH) in animal models. This was a multi-centre, double-blind, placebo-controlled, parallel-group randomised clinical trial to evaluate the safety, pharmacokinetics and efficacy of 28 days of SFX-01 300 mg BD in patients aged 18-80 with spontaneous SAH and high blood load on CT. Primary outcomes were (1) safety, (2) plasma and CSF SFN and metabolite levels and (3) vasospasm on transcranial doppler ultrasound. Secondary outcomes included CSF haptoglobin and malondialdehyde and clinical outcome on the modified Rankin Scale (mRS) and SAH outcome tool (SAHOT). A total of 105 patients were randomised (54 SFX-01, 51 placebo). There were no differences in adverse events other than nausea (9 SFX-01 (16.7%), 1 placebo (2.0%)). SFN, SFN-glutathione and SFN-N-acetyl-cysteine AUC<sub>last</sub> were 16.2, 277 and 415 h × ng/ml. Plasma SFN was higher in GSTT1 null individuals (t = 2.40, p = 0.023). CSF levels were low with many samples below the lower limit of quantification and predicted by the CSF/serum albumin ratio (R<sup>2</sup> = 0.182, p = 0.039). There was no difference in CSF haptoglobin (1.981 95%CI 0.992-3.786, p = 0.052) or malondialdehyde (1.12 95%CI 0.7477-1.687, p = 0.572) or middle cerebral artery flow velocity (1.04 95%CI 0.903-1.211, p = 0.545) or functional outcome (mRS 1.647 95%CI 0.721-3.821, p = 0.237, SAHOT 1.082 95%CI 0.464-2.525, p = 0.855). SFX-01 is safe and effective for the delivery of SFN in acutely unwell patients. SFN penetrated CSF less than expected and did not reduce large vessel vasospasm or improve outcome. Trial registration: NCT02614742 clinicaltrials.gov.</p>\",\"PeriodicalId\":23237,\"journal\":{\"name\":\"Translational Stroke Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-07-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational Stroke Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12975-024-01278-1\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Stroke Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12975-024-01278-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

SFX-01 是一种新型药物,用于在临床上释放莱菔硫烷(SFN)。SFN是一种强效的红细胞核因子2相关因子2激活剂,能减少炎症和氧化,改善动物模型蛛网膜下腔出血(SAH)后的预后。这是一项多中心、双盲、安慰剂对照、平行组随机临床试验,目的是评估自发性蛛网膜下腔出血(SAH)和 CT 血容量高的 18-80 岁患者服用 28 天 SFX-01 300 毫克 BD 的安全性、药代动力学和疗效。主要结果包括:(1) 安全性;(2) 血浆和脑脊液 SFN 及代谢物水平;(3) 经颅多普勒超声显示的血管痉挛。次要结果包括 CSF 血红蛋白和丙二醛以及改良兰金量表(mRS)和 SAH 结果工具(SAHOT)的临床结果。共有105名患者接受了随机治疗(54名SFX-01患者,51名安慰剂患者)。除恶心(9例SFX-01(16.7%),1例安慰剂(2.0%))外,其他不良反应无差异。SFN、SFN-谷胱甘肽和SFN-N-乙酰-半胱氨酸的AUClast分别为16.2、277和415小时×纳克/毫升。GSTT1 基因无效者的血浆 SFN 水平更高(t = 2.40,p = 0.023)。CSF水平较低,许多样本低于定量下限,可通过CSF/血清白蛋白比值预测(R2 = 0.182,p = 0.039)。CSF 血红蛋白(1.981 95%CI 0.992-3.786,p = 0.052)或丙二醛(1.12 95%CI 0.7477-1.687,p = 0.572)或大脑中动脉流速(1.04 95%CI 0.903-1.211, p = 0.545)或功能结果(mRS 1.647 95%CI 0.721-3.821, p = 0.237, SAHOT 1.082 95%CI 0.464-2.525, p = 0.855)。SFX-01可安全有效地为急性病患者提供SFN。SFN穿透CSF的程度低于预期,但并未减轻大血管痉挛或改善预后。试验注册:NCT02614742 clinicaltrials.gov。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A Randomised Controlled Trial of SFX-01 After Subarachnoid Haemorrhage - The SAS Study.

A Randomised Controlled Trial of SFX-01 After Subarachnoid Haemorrhage - The SAS Study.

SFX-01 is a novel drug for clinical delivery of sulforaphane (SFN). SFN is a potent nuclear factor erythroid 2-related factor 2 activator that reduces inflammation and oxidation, improving outcomes after subarachnoid haemorrhage (SAH) in animal models. This was a multi-centre, double-blind, placebo-controlled, parallel-group randomised clinical trial to evaluate the safety, pharmacokinetics and efficacy of 28 days of SFX-01 300 mg BD in patients aged 18-80 with spontaneous SAH and high blood load on CT. Primary outcomes were (1) safety, (2) plasma and CSF SFN and metabolite levels and (3) vasospasm on transcranial doppler ultrasound. Secondary outcomes included CSF haptoglobin and malondialdehyde and clinical outcome on the modified Rankin Scale (mRS) and SAH outcome tool (SAHOT). A total of 105 patients were randomised (54 SFX-01, 51 placebo). There were no differences in adverse events other than nausea (9 SFX-01 (16.7%), 1 placebo (2.0%)). SFN, SFN-glutathione and SFN-N-acetyl-cysteine AUClast were 16.2, 277 and 415 h × ng/ml. Plasma SFN was higher in GSTT1 null individuals (t = 2.40, p = 0.023). CSF levels were low with many samples below the lower limit of quantification and predicted by the CSF/serum albumin ratio (R2 = 0.182, p = 0.039). There was no difference in CSF haptoglobin (1.981 95%CI 0.992-3.786, p = 0.052) or malondialdehyde (1.12 95%CI 0.7477-1.687, p = 0.572) or middle cerebral artery flow velocity (1.04 95%CI 0.903-1.211, p = 0.545) or functional outcome (mRS 1.647 95%CI 0.721-3.821, p = 0.237, SAHOT 1.082 95%CI 0.464-2.525, p = 0.855). SFX-01 is safe and effective for the delivery of SFN in acutely unwell patients. SFN penetrated CSF less than expected and did not reduce large vessel vasospasm or improve outcome. Trial registration: NCT02614742 clinicaltrials.gov.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Translational Stroke Research
Translational Stroke Research CLINICAL NEUROLOGY-NEUROSCIENCES
CiteScore
13.80
自引率
4.30%
发文量
130
审稿时长
6-12 weeks
期刊介绍: Translational Stroke Research covers basic, translational, and clinical studies. The Journal emphasizes novel approaches to help both to understand clinical phenomenon through basic science tools, and to translate basic science discoveries into the development of new strategies for the prevention, assessment, treatment, and enhancement of central nervous system repair after stroke and other forms of neurotrauma. Translational Stroke Research focuses on translational research and is relevant to both basic scientists and physicians, including but not restricted to neuroscientists, vascular biologists, neurologists, neuroimagers, and neurosurgeons.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信