Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial.
BMJ Open
; 13(4): e068179, 2023 04 13.
Article
in English
| MEDLINE | ID: covidwho-2298181
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. PRIMARYOUTCOMES:
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19
Type of study:
Cohort study
/
Experimental Studies
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Journal:
BMJ Open
Year:
2023
Document Type:
Article
Affiliation country:
Bmjopen-2022-068179
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