NCT05007678: DEFEAT-COVID

Targeting de Novo Pyrimidine Biosynthesis by Leflunomide for the Treatment of COVID-19 Virus Disease

Completed Phase 3 Last updated 27 February 2023

What this trial tests

Phase 3 trial testing leflunomide in COVID-19 in 178 participants. Completed in 1 July 2022.

Timeline

16 September 2020

Primary endpoint
1 July 2022

1 July 2022

Quick facts

Lead sponsor	Ashford and St. Peter's Hospitals NHS Trust
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	178
Start date	16 September 2020
Primary completion	1 July 2022
Estimated completion	1 July 2022
Sites	1 location across United Kingdom

Drugs / interventions tested

• leflunomide (LEFLUNOMIDE) — full drug profile →

Conditions studied

• COVID-19 — all drugs for COVID-19 →

Sponsor

Ashford and St. Peter's Hospitals NHS Trust

Who can join

18 and older, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The global COVID-19 pandemic has caused unprecedented strain on health care services around the world.The absence of specific anti-viral medications to treat the underlying infection led to a proliferation of clinical studies and trials aimed at re-purposing existing medications.

Human dihydroorotate dehydrogenase (DHODH) is vital enzyme utilised by viruses to replicate in the host cell. Leflunomide, a drug that is already licenced to treat rheumatoid arthritis, is a potent inhibitor of the enzyme DHODH. Importantly, this drug has dual anti-viral and anti-inflammatory properties so it targets viral replication and suppresses host inflammatory response which plays a role at more progressive stages of infection.

DEFEAT-COVID is a multi-site, international, interventional, pragmatic, parallel group design, open label, randomised CTIMP with a pilot phase that will allow to adapt procedures and assessments if required.

A phase III clinical trial of leflunomide for treating COVID-19 has been registered in China, Registration number: ChiCTR2000030058). The current proposal extends the original clinical study of leflunomide in China (People's Hospital of Wuhan University) to the UK through a structured collaboration.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication.
   Ning Q, Wu D, Wang X, Xi D, et al · · 2022 · cited 64× · PMID 35197452 · DOI 10.1038/s41392-022-00907-1
2. Ferroptosis: mechanisms and therapeutic targets.
   Zhou Q, Meng Y, Le J, Sun Y, et al · · 2024 · cited 32× · PMID 39568772 · DOI 10.1002/mco2.70010
3. Multi-omics for COVID-19: driving development of therapeutics and vaccines.
   Guo M, Xiong M, Peng J, Guan T, et al · · 2023 · cited 14× · PMID 37936830 · DOI 10.1093/nsr/nwad161
4. Harnessing ferroptosis to transform glioblastoma therapy and surmount treatment resistance.
   Singh S, Mohapatra I, Barik D, Zheng H, et al · · 2025 · cited 5× · PMID 41057317 · DOI 10.1038/s41420-025-02744-x
5. Leflunomide treatment for patients hospitalised with COVID-19: DEFEAT-COVID randomised controlled trial.
   Kralj-Hans I, Li K, Wesek A, Lamorgese A, et al · · 2023 · cited 4× · PMID 37055207 · DOI 10.1136/bmjopen-2022-068179