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

التفاصيل البيبلوغرافية
العنوان: SFX-01 in hospitalised patients with community-acquired pneumonia during the COVID-19 pandemic: a double-blind, randomised, placebo-controlled trial.
المؤلفون: Long MB; Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.; These authors contributed equally., Abo-Leyah H; Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.; These authors contributed equally., Giam YH; Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK., Vadiveloo T; Centre for Healthcare Randomised Trials, University of Aberdeen, Aberdeen, UK., Hull RC; Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK., Keir HR; Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK., Pembridge T; Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK., Alferes De Lima D; Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK., Delgado L; Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK., Inglis SK; Tayside Clinical Trials Unit, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK., Hughes C; Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK., Gilmour A; Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK., Gierlinski M; Computational Biology, School of Life Sciences, University of Dundee, Dundee, UK., New BJM; NHS Tayside, Ninewells Hospital, Dundee, UK., MacLennan G; Centre for Healthcare Randomised Trials, University of Aberdeen, Aberdeen, UK., Dinkova-Kostova AT; Division of Cellular and Systems Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.; Department of Pharmacology and Molecular Sciences and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Chalmers JD; Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
المصدر: ERJ open research [ERJ Open Res] 2024 Mar 11; Vol. 10 (2). Date of Electronic Publication: 2024 Mar 11 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: European Respiratory Society Country of Publication: England NLM ID: 101671641 Publication Model: eCollection Cited Medium: Print ISSN: 2312-0541 (Print) Linking ISSN: 23120541 NLM ISO Abbreviation: ERJ Open Res Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Sheffield : European Respiratory Society, [2015]-
مستخلص: 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, log 2 FC >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.
Competing Interests: Conflict of interest: H.R. Keir reports receiving personal fees for educational lecture from Insmed Inc., outside the submitted work. Conflict of interest: A.T. Dinkova-Kostova participates on the Evgen Pharma Scientific Advisory Board, outside the submitted work. Conflict of interest: J.D. Chalmers reports support for the present manuscript from Lifearc; grants or contracts from AstraZeneca, Genentech, Gilead Sciences, GlaxoSmithKline, Insmed, Grifols, Novartis and Boehringer Ingelheim, outside the submitted work; consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio and Zambon, outside the submitted work; and is an associate editor of this journal. Conflict of interest: The remaining authors have nothing to disclose.
(Copyright ©The authors 2024.)
References: Nutrients. 2021 Feb 12;13(2):. (PMID: 33673203)
Clin Infect Dis. 2021 Dec 16;73(12):2257-2264. (PMID: 33515252)
Cell Mol Life Sci. 2022 Nov 1;79(11):579. (PMID: 36319916)
J Allergy Clin Immunol Pract. 2016 Sep-Oct;4(5):932-40. (PMID: 27130714)
Respir Res. 2015 Sep 15;16:106. (PMID: 26369337)
J Infect Dis. 2020 Oct 7;222(Suppl 7):S570-S576. (PMID: 30849172)
Respir Res. 2016 Jul 22;17(1):89. (PMID: 27450419)
Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15926-31. (PMID: 18838692)
PLoS One. 2016 Nov 10;11(11):e0163716. (PMID: 27832073)
Front Pharmacol. 2022 Jan 21;13:805508. (PMID: 35126161)
Eur Respir J. 2022 Aug 10;60(2):. (PMID: 35710264)
Nature. 2021 Oct;598(7880):342-347. (PMID: 34464958)
Nat Commun. 2020 Oct 2;11(1):4938. (PMID: 33009401)
N Engl J Med. 2021 Feb 25;384(8):693-704. (PMID: 32678530)
J Infect Dis. 2021 Feb 24;223(4):562-567. (PMID: 33206973)
Ann Am Thorac Soc. 2021 Jul;18(7):1087-1097. (PMID: 34242148)
Eur Respir J. 2021 Apr 15;57(4):. (PMID: 33692120)
Chem Res Toxicol. 2011 Apr 18;24(4):515-21. (PMID: 21391649)
Lancet Respir Med. 2020 Apr;8(4):420-422. (PMID: 32085846)
Mult Scler Relat Disord. 2019 May;30:257-261. (PMID: 30851639)
Nat Med. 2021 May;27(5):904-916. (PMID: 33879890)
Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):847-51. (PMID: 17416783)
Lancet. 2021 May 01;397(10285):1637-1645. (PMID: 33933206)
J Immunol. 2016 Oct 1;197(7):2864-79. (PMID: 27566827)
PLoS One. 2021 Feb 16;16(2):e0245986. (PMID: 33592002)
Eur Respir J. 2000 Sep;16(3):534-54. (PMID: 11028671)
Am J Respir Cell Mol Biol. 2002 Feb;26(2):175-82. (PMID: 11804867)
Am J Respir Cell Mol Biol. 2011 Sep;45(3):557-65. (PMID: 21216970)
Nat Commun. 2016 May 23;7:11624. (PMID: 27211851)
Respir Med. 2004 Jul;98(7):669-76. (PMID: 15250234)
Molecules. 2019 Oct 06;24(19):. (PMID: 31590459)
Nature. 2020 Aug;584(7821):463-469. (PMID: 32717743)
Sci Transl Med. 2017 Jun 14;9(394):. (PMID: 28615356)
Cancer Prev Res (Phila). 2014 Aug;7(8):813-823. (PMID: 24913818)
Lancet Respir Med. 2020 Dec;8(12):1233-1244. (PMID: 33075298)
Trends Pharmacol Sci. 2023 Mar;44(3):137-149. (PMID: 36628798)
Nutrients. 2021 Dec 20;13(12):. (PMID: 34960110)
Lancet. 2022 Jul 30;400(10349):359-368. (PMID: 35908569)
Pharmaceuticals (Basel). 2021 Oct 26;14(11):. (PMID: 34832864)
Sci Rep. 2020 Apr 2;10(1):5822. (PMID: 32242086)
Biochem Biophys Res Commun. 2011 Feb 4;405(1):146-51. (PMID: 21219867)
Am J Respir Cell Mol Biol. 2012 Nov;47(5):688-97. (PMID: 22842495)
Lancet Reg Health Eur. 2022 Oct;21:100473. (PMID: 35965672)
Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2399-403. (PMID: 1549603)
Exp Ther Med. 2018 Jun;15(6):4911-4915. (PMID: 29805514)
Sci Transl Med. 2011 Apr 13;3(78):78ra32. (PMID: 21490276)
Commun Biol. 2022 Mar 18;5(1):242. (PMID: 35304580)
تواريخ الأحداث: Date Created: 20240312 Latest Revision: 20240313
رمز التحديث: 20240313
مُعرف محوري في PubMed: PMC10926007
DOI: 10.1183/23120541.00917-2023
PMID: 38469377
قاعدة البيانات: MEDLINE
الوصف
تدمد:2312-0541
DOI:10.1183/23120541.00917-2023