Dataset Information

Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial.

ABSTRACT:

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.

SUBMITTER: Kralj-Hans I

PROVIDER: S-EPMC10105917 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial.

Kralj-Hans Ines I Li Kuo K Wesek Adrian A Lamorgese Alexia A Omar Fatima F Ranasinghe Kapila K McGee Megan M Brack Kieran K Li Shiliang S Aggarwal Ritesh R Bulle Ajay A Kodre Aparna A Sharma Shashank S Fluck David D John Isaac I Sharma Pankaj P Belsey Jonathan D JD Li Ling L Seshasai Sreenivasa Rao Kondapally SRK Li Hong Lin HL Marczin Nandor N Chen Zhong Z

BMJ open 20230413 4

<h4>Objective</h4>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.<h4>Design</h4>Prospective, open-label, multicentre, stratified, randomised clinical trial.<h4>Setting</h4>Five hospitals in UK and India, from September 2020 to May 2021.<h4>Participants</h4>Adults with PCR confirmed COVID-19 infection with moderate/critical symptoms within 15 days of onset.<h4> ...[more]

PMID: 37055207

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Dataset Information

Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial.

Objective

Design

Setting

Participants

Intervention

Primary outcomes

Results

Conclusion

Trial registration numbers

Publications

Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial.

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