SFX-01 in hospitalised patients with community-acquired pneumonia during the COVID-19 pandemic: a double-blind, randomised, placebo-controlled trial.

IF 4.3 3区医学 Q1 RESPIRATORY SYSTEM

ERJ Open Research Pub Date : 2024-03-11 eCollection Date: 2024-03-01 DOI:10.1183/23120541.00917-2023

Merete B Long, Hani Abo-Leyah, Yan Hui Giam, Thenmalar Vadiveloo, Rebecca C Hull, Holly R Keir, Thomas Pembridge, Daniela Alferes De Lima, Lilia Delgado, Sarah K Inglis, Chloe Hughes, Amy Gilmour, Marek Gierlinski, Benjamin J M New, Graeme MacLennan, Albena T Dinkova-Kostova, James D Chalmers

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引用次数: 0

Abstract

Introduction: Sulforaphane can induce the transcription factor, Nrf2, promoting antioxidant and anti-inflammatory responses. In this study, hospitalised patients with community-acquired pneumonia (CAP) were treated with stabilised synthetic sulforaphane (SFX-01) to evaluate impact on clinical status and inflammation.

Methods: Double-blind, randomised, placebo-controlled trial of SFX-01 (300 mg oral capsule, once daily for 14 days) conducted in Dundee, UK, between November 2020 and May 2021. Patients had radiologically confirmed CAP and CURB-65 (confusion, urea >7 mmol·L^-1, respiratory rate ≥30 breaths·min^-1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years) score ≥1. The primary outcome was the seven-point World Health Organization clinical status scale at day 15. Secondary outcomes included time to clinical improvement, length of stay and mortality. Effects on Nrf2 activity and inflammation were evaluated on days 1, 8 and 15 by measurement of 45 serum cytokines and mRNA sequencing of peripheral blood leukocytes.

Results: The trial was terminated prematurely due to futility with 133 patients enrolled. 65 patients were randomised to SFX-01 treatment and 68 patients to placebo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was the cause of CAP in 103 (77%) cases. SFX-01 treatment did not improve clinical status at day 15 (adjusted OR 0.87, 95% CI 0.41-1.83; p=0.71), time to clinical improvement (adjusted hazard ratio (aHR) 1.02, 95% CI 0.70-1.49), length of stay (aHR 0.84, 95% CI 0.56-1.26) or 28-day mortality (aHR 1.45, 95% CI 0.67-3.16). The expression of Nrf2 targets and pro-inflammatory genes, including interleukin (IL)-6, IL-1β and tumour necrosis factor-α, was not significantly changed by SFX-01 treatment. At days 8 and 15, respectively, 310 and 42 significant differentially expressed genes were identified between groups (false discovery rate adjusted p<0.05, log₂FC >1).

Conclusion: SFX-01 treatment did not improve clinical status or modulate key Nrf2 targets in patients with CAP primarily due to SARS-CoV-2 infection.

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SFX-01在COVID-19大流行期间用于社区获得性肺炎住院患者：双盲、随机、安慰剂对照试验。

导言菔素可诱导转录因子Nrf2，促进抗氧化和抗炎反应。在这项研究中，住院的社区获得性肺炎（CAP）患者接受了稳定合成舒拉萘烷（SFX-01）的治疗，以评估其对临床状态和炎症的影响：2020年11月至2021年5月期间，在英国邓迪对SFX-01（300毫克口服胶囊，每天一次，连续14天）进行双盲、随机、安慰剂对照试验。患者经放射学确诊为 CAP 和 CURB-65（意识模糊、尿素 >7 mmol-L-1、呼吸频率≥30 次/分-1、血压结果）：试验因无效而提前结束，共有 133 名患者入选。65名患者随机接受SFX-01治疗，68名患者随机接受安慰剂治疗。103例（77%）患者的CAP病因是严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）感染。SFX-01治疗并未改善第15天的临床状态（调整后OR值为0.87，95% CI为0.41-1.83；P=0.71）、临床改善时间（调整后危险比（aHR）为1.02，95% CI为0.70-1.49）、住院时间（aHR为0.84，95% CI为0.56-1.26）或28天死亡率（aHR为1.45，95% CI为0.67-3.16）。Nrf2靶点和促炎基因（包括白细胞介素（IL）-6、IL-1β和肿瘤坏死因子-α）的表达在SFX-01治疗后没有显著变化。在第8天和第15天，组间分别发现了310个和42个显著差异表达基因（假发现率调整后p2FC>1）：结论：SFX-01治疗并不能改善主要由SARS-CoV-2感染引起的CAP患者的临床状况，也不能调节关键的Nrf2靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ERJ Open Research Medicine-Pulmonary and Respiratory Medicine

CiteScore

6.20

自引率

4.30%

发文量

273

审稿时长

8 weeks

期刊介绍： ERJ Open Research is a fully open access original research journal, published online by the European Respiratory Society. The journal aims to publish high-quality work in all fields of respiratory science and medicine, covering basic science, clinical translational science and clinical medicine. The journal was created to help fulfil the ERS objective to disseminate scientific and educational material to its members and to the medical community, but also to provide researchers with an affordable open access specialty journal in which to publish their work.