TY - JOUR
T1 - SFX-01 in hospitalised patients with community-acquired pneumonia during the COVID-19 pandemic
T2 - a double-blind, randomised, placebo-controlled trial
AU - Long, Merete B.
AU - Abo-Leyah, Hani
AU - Giam, Yan Hui
AU - Vadiveloo, Thenmalar
AU - Hull, Rebecca C.
AU - Keir, Holly R.
AU - Pembridge, Thomas
AU - De Lima, Daniela Alferes
AU - Delgado, Lilia
AU - Inglis, Sarah K.
AU - Hughes, Chloe
AU - Gilmour, Amy
AU - Gierlinski, Marek
AU - New, Benjamin J.M.
AU - Maclennan, Graeme
AU - Dinkova-Kostova, Albena T.
AU - Chalmers, James D.
N1 - We acknowledge the members of the STAR-COVID data monitoring committee: Aran Singanayagam (Imperial College, London, UK), Timothy Hinks (University of Oxford, Oxford, UK), Oriol Sibila (Hospital Clinic, Barcelona, Spain), Alex McConnachie (University of Glasgow, Glasgow, UK) and Petra Rauchhaus (University of Dundee, Dundee, UK). This trial was delivered by Tayside Clinical Trials Unit, a UKCRC registered clinical trials unit. Thanks to Clare Clarke, Jennifer Taylor, Angela Strachan, Heather Loftus and Jodie Strachan (Ninewells Hospital and Medical School, Dundee, UK) and Diane Cassidy (University of Dundee). We thank all study participants and their families.
PY - 2024/3
Y1 - 2024/3
N2 - 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, log2 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.
AB - 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, log2 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.
UR - http://www.scopus.com/inward/record.url?scp=85187909521&partnerID=8YFLogxK
U2 - 10.1183/23120541.00917-2023
DO - 10.1183/23120541.00917-2023
M3 - Article
AN - SCOPUS:85187909521
SN - 2312-0541
VL - 10
JO - ERJ Open Research
JF - ERJ Open Research
IS - 2
M1 - 00917-2023
ER -