PMID- 37055207

OWN - NLM
STAT- MEDLINE
DCOM- 20230417
LR - 20230423
IS - 2044-6055 (Electronic)
IS - 2044-6055 (Linking)
VI - 13
IP - 4
DP - 2023 Apr 13
TI - Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID
randomised controlled trial.
PG - e068179
LID - 10.1136/bmjopen-2022-068179 [doi]
LID - e068179
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.
CI - © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No
commercial re-use. See rights and permissions. Published by BMJ.
FAU - Kralj-Hans, Ines
AU - Kralj-Hans I
AUID- ORCID: 0000-0001-7401-6281
AD - Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK i.kralj-
hans@nhs.net.
FAU - Li, Kuo
AU - Li K
AD - Imperial College, London, UK.
FAU - Wesek, Adrian
AU - Wesek A
AD - Imperial College, London, UK.
FAU - Lamorgese, Alexia
AU - Lamorgese A
AD - JB Medical Ltd, Sudbury, UK.
FAU - Omar, Fatima
AU - Omar F
AD - Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
FAU - Ranasinghe, Kapila
AU - Ranasinghe K
AD - Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
FAU - McGee, Megan
AU - McGee M
AD - Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
FAU - Brack, Kieran
AU - Brack K
AD - Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
FAU - Li, Shiliang
AU - Li S
AD - East China University of Science and Technology, Shanghai, China.
FAU - Aggarwal, Ritesh
AU - Aggarwal R
AD - Max Hospital, Delhi, India.
FAU - Bulle, Ajay
AU - Bulle A
AD - Meditrina Institute of Medical Science, Nagpur, India.
FAU - Kodre, Aparna
AU - Kodre A
AD - Noble Hospital, Pune, India.
FAU - Sharma, Shashank
AU - Sharma S
AD - St Peters Hospital Emergency Department, Ashford and Saint Peter's Hospitals
NHS
Trust, Chertsey, UK.
FAU - Fluck, David
AU - Fluck D
AD - Cardiology, Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
FAU - John, Isaac
AU - John I
AD - Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
FAU - Sharma, Pankaj
AU - Sharma P
AD - Royal Holloway University of London, Egham, UK.
FAU - Belsey, Jonathan D
AU - Belsey JD
AD - JB Medical Ltd, Sudbury, UK.
FAU - Li, Ling
AU - Li L
AUID- ORCID: 0000-0002-4026-0216
AD - Department of Engineering, City University, London, UK.
FAU - Seshasai, Sreenivasa Rao Kondapally
AU - Seshasai SRK
AD - St George's University Hospitals NHS Foundation Trust, London, UK.
FAU - Li, Hong Lin
AU - Li HL
AD - Shanghai Key Laboratory of New Drug Design, Shanghai, China.
FAU - Marczin, Nandor
AU - Marczin N
AD - Imperial College, London, UK.
FAU - Chen, Zhong
AU - Chen Z
AD - Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
CN - DEFEAT-COVID Investigators
LA - eng
SI - ClinicalTrials.gov/NCT05007678
PT - Journal Article
PT - Randomized Controlled Trial
PT - Research Support, Non-U.S. Gov't
DEP - 20230413
PL - England
TA - BMJ Open
JT - BMJ open
JID - 101552874
RN - G162GK9U4W (Leflunomide)
RN - ICJ93X8X90 (canertinib dihydrochloride)
RN - S88TT14065 (Oxygen)
SB - IM
MH - Adult
MH - Humans
MH - Female
MH - Middle Aged
MH - Aged
MH - Male
MH - *COVID-19
MH - Leflunomide/therapeutic use
MH - SARS-CoV-2
MH - Prospective Studies
MH - Treatment Outcome
MH - Oxygen
PMC - PMC10105917
OTO - NOTNLM
OT - COVID-19
OT - INFECTIOUS DISEASES
OT - Respiratory infections
COIS- Competing interests: None declared.
FIR - Sharma, Shashank
IR - Sharma S
FIR - McGee, Megan
IR - McGee M
FIR - Brack, Kieran
IR - Brack K
FIR - Aquino, Maia
IR - Aquino M
FIR - Pereira, Rita
IR - Pereira R
FIR - Frost, Vicky
IR - Frost V
FIR - Gibson, Kirsty
IR - Gibson K
FIR - Croft, Maria
IR - Croft M
FIR - Omar, Fatima
IR - Omar F
FIR - Ranasinghe, Kapila
IR - Ranasinghe K
FIR - Mahendran, Siva
IR - Mahendran S
FIR - Joseph, Anna
IR - Joseph A
FIR - Grout, Maggie
IR - Grout M
FIR - Dewan, Arun
IR - Dewan A
FIR - Aggarwal, Ritesh
IR - Aggarwal R
FIR - Bulle, Ajay
IR - Bulle A
FIR - Kodre, Aparna
IR - Kodre A
EDAT- 2023/04/14 06:00
MHDA- 2023/04/17 06:41
CRDT- 2023/04/13 21:42
PHST- 2023/04/17 06:41 [medline]
PHST- 2023/04/13 21:42 [entrez]
PHST- 2023/04/14 06:00 [pubmed]
AID - bmjopen-2022-068179 [pii]
AID - 10.1136/bmjopen-2022-068179 [doi]
PST - epublish
SO - BMJ Open. 2023 Apr 13;13(4):e068179. doi: 10.1136/bmjopen-2022-068179.