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Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial.
Kralj-Hans, Ines; Li, Kuo; Wesek, Adrian; Lamorgese, Alexia; Omar, Fatima; Ranasinghe, Kapila; McGee, Megan; Brack, Kieran; Li, Shiliang; Aggarwal, Ritesh; Bulle, Ajay; Kodre, Aparna; Sharma, Shashank; Fluck, David; John, Isaac; Sharma, Pankaj; Belsey, Jonathan D; Li, Ling; Seshasai, Sreenivasa Rao Kondapally; Li, Hong Lin; Marczin, Nandor; Chen, Zhong.
  • Kralj-Hans I; Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK i.kralj-hans@nhs.net.
  • Li K; Imperial College, London, UK.
  • Wesek A; Imperial College, London, UK.
  • Lamorgese A; JB Medical Ltd, Sudbury, UK.
  • Omar F; Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
  • Ranasinghe K; Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
  • McGee M; Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
  • Brack K; Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
  • Li S; East China University of Science and Technology, Shanghai, China.
  • Aggarwal R; Max Hospital, Delhi, India.
  • Bulle A; Meditrina Institute of Medical Science, Nagpur, India.
  • Kodre A; Noble Hospital, Pune, India.
  • Sharma S; St Peters Hospital Emergency Department, Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
  • Fluck D; Cardiology, Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
  • John I; Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
  • Sharma P; Royal Holloway University of London, Egham, UK.
  • Belsey JD; JB Medical Ltd, Sudbury, UK.
  • Li L; Department of Engineering, City University, London, UK.
  • Seshasai SRK; St George's University Hospitals NHS Foundation Trust, London, UK.
  • Li HL; Shanghai Key Laboratory of New Drug Design, Shanghai, China.
  • Marczin N; Imperial College, London, UK.
  • Chen Z; Ashford and Saint Peter's Hospitals NHS Trust, Chertsey, UK.
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. 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.
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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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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