TY - JOUR
T1 - Leflunomide treatment for patients hospitalised with COVID-19
T2 - DEFEAT-COVID randomised controlled trial
AU - Kralj-Hans, Ines
AU - Li, Kuo
AU - Wesek, Adrian
AU - Lamorgese, Alexia
AU - Omar, Fatima
AU - Ranasinghe, Kapila
AU - McGee, Megan
AU - Brack, Kieran
AU - Li, Shiliang
AU - Aggarwal, Ritesh
AU - Bulle, Ajay
AU - Kodre, Aparna
AU - Sharma, Shashank
AU - Fluck, David
AU - John, Isaac
AU - Sharma, Pankaj
AU - Belsey, Jonathan D.
AU - Li, Ling
AU - Seshasai, Sreenivasa Rao Kondapally
AU - Li, Hong Lin
AU - Marczin, Nandor
AU - Chen, Zhong
N1 - Publisher Copyright:
© 2023 BMJ Publishing Group. All rights reserved.
PY - 2023/4/13
Y1 - 2023/4/13
N2 - Objective To evaluate the clinical efficacy and safety of leflunomide (L) added to the standard-of-care (SOC) treatment in COVID-19 patients hospitalised with moderate/critical clinical symptoms. Design Prospective, open-label, multicentre, stratified, randomised clinical trial. Setting Five hospitals in UK and India, from September 2020 to May 2021. Participants Adults with PCR confirmed COVID-19 infection with moderate/critical symptoms within 15 days of onset. Intervention Leflunomide 100 mg/day (3 days) followed by 10-20 mg/day (7 days) added to standard care. Primary outcomes The time to clinical improvement (TTCI) defined as two-point reduction on a clinical status scale or live discharge prior to 28 days; safety profile measured by the incidence of adverse events (AEs) within 28 days. Results Eligible patients (n=214; age 56.3±14.9 years; 33% female) were randomised to SOC+L (n=104) and SOC group (n=110), stratified according to their clinical risk profile. TTCI was 7 vs 8 days in SOC+L vs SOC group (HR 1.317; 95% CI 0.980 to 1.768; p=0.070). Incidence of serious AEs was similar between the groups and none was attributed to leflunomide. In sensitivity analyses, excluding 10 patients not fulfilling the inclusion criteria and 3 who withdrew consent before leflunomide treatment, TTCI was 7 vs 8 days (HR 1.416, 95% CI 1.041 to 1.935; p=0.028), indicating a trend in favour of the intervention group. All-cause mortality rate was similar between groups, 9/104 vs 10/110. Duration of oxygen dependence was shorter in the SOC+L group being a median 6 days (IQR 4-8) compared with 7 days (IQR 5-10) in SOC group (p=0.047). Conclusion Leflunomide, added to the SOC treatment for COVID-19, was safe and well tolerated but had no major impact on clinical outcomes. It may shorten the time of oxygen dependence by 1 day and thereby improve TTCI/hospital discharge in moderately affected COVID-19 patients. Trial registration numbers EudraCT Number: 2020-002952-18, NCT05007678.
AB - Objective To evaluate the clinical efficacy and safety of leflunomide (L) added to the standard-of-care (SOC) treatment in COVID-19 patients hospitalised with moderate/critical clinical symptoms. Design Prospective, open-label, multicentre, stratified, randomised clinical trial. Setting Five hospitals in UK and India, from September 2020 to May 2021. Participants Adults with PCR confirmed COVID-19 infection with moderate/critical symptoms within 15 days of onset. Intervention Leflunomide 100 mg/day (3 days) followed by 10-20 mg/day (7 days) added to standard care. Primary outcomes The time to clinical improvement (TTCI) defined as two-point reduction on a clinical status scale or live discharge prior to 28 days; safety profile measured by the incidence of adverse events (AEs) within 28 days. Results Eligible patients (n=214; age 56.3±14.9 years; 33% female) were randomised to SOC+L (n=104) and SOC group (n=110), stratified according to their clinical risk profile. TTCI was 7 vs 8 days in SOC+L vs SOC group (HR 1.317; 95% CI 0.980 to 1.768; p=0.070). Incidence of serious AEs was similar between the groups and none was attributed to leflunomide. In sensitivity analyses, excluding 10 patients not fulfilling the inclusion criteria and 3 who withdrew consent before leflunomide treatment, TTCI was 7 vs 8 days (HR 1.416, 95% CI 1.041 to 1.935; p=0.028), indicating a trend in favour of the intervention group. All-cause mortality rate was similar between groups, 9/104 vs 10/110. Duration of oxygen dependence was shorter in the SOC+L group being a median 6 days (IQR 4-8) compared with 7 days (IQR 5-10) in SOC group (p=0.047). Conclusion Leflunomide, added to the SOC treatment for COVID-19, was safe and well tolerated but had no major impact on clinical outcomes. It may shorten the time of oxygen dependence by 1 day and thereby improve TTCI/hospital discharge in moderately affected COVID-19 patients. Trial registration numbers EudraCT Number: 2020-002952-18, NCT05007678.
KW - COVID-19
KW - INFECTIOUS DISEASES
KW - Respiratory infections
UR - https://www.scopus.com/pages/publications/85152383833
U2 - 10.1136/bmjopen-2022-068179
DO - 10.1136/bmjopen-2022-068179
M3 - 文章
C2 - 37055207
AN - SCOPUS:85152383833
SN - 2044-6055
VL - 13
JO - BMJ Open
JF - BMJ Open
IS - 4
M1 - e068179
ER -
