Suppr
超能文献

COVID-19大流行期间住院社区获得性肺炎患者使用SFX-01的双盲、随机、安慰剂对照试验

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

作者信息

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

机构信息

Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.

These authors contributed equally.

出版信息

ERJ Open Res. 2024 Mar 11;10(2). doi: 10.1183/23120541.00917-2023. eCollection 2024 Mar.

DOI:10.1183/23120541.00917-2023

PMID:38469377

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10926007/

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, respiratory rate ≥30 breaths·min, 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, logFC >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.

摘要

引言

萝卜硫素可诱导转录因子Nrf2，促进抗氧化和抗炎反应。在本研究中，对住院的社区获得性肺炎（CAP）患者使用稳定的合成萝卜硫素（SFX - 01）进行治疗，以评估其对临床状况和炎症的影响。

方法

2020年11月至2021年5月在英国邓迪进行了一项关于SFX - 01（300毫克口服胶囊，每日一次，共14天）的双盲、随机、安慰剂对照试验。患者经放射学确诊为CAP且CURB - 65（意识模糊、尿素>7 mmol·L、呼吸频率≥30次/分钟、血压<90 mmHg（收缩压）或≤60 mmHg（舒张压）、年龄≥65岁）评分≥1。主要结局是第15天的七点世界卫生组织临床状况量表。次要结局包括临床改善时间、住院时间和死亡率。在第1、8和15天通过测量45种血清细胞因子和外周血白细胞的mRNA测序评估对Nrf2活性和炎症的影响。

结果

由于无效性，该试验提前终止，共纳入133例患者。65例患者被随机分配接受SFX - 01治疗，68例患者接受安慰剂治疗。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染是103例（77%）CAP病例的病因。SFX - 01治疗在第15天未改善临床状况（调整后的OR为0.87，95%CI为0.41 - 1.83；p = 0.71）、临床改善时间（调整后的风险比（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）。SFX - 01治疗未显著改变Nrf2靶点和促炎基因的表达，包括白细胞介素（IL）-6、IL - 1β和肿瘤坏死因子-α。在第8天和第15天，两组之间分别鉴定出310个和42个显著差异表达基因（错误发现率调整p<0.05，logFC>1）。