Confirmed Covid-19 infection by RT-PCR
Conditions
Interventions
Trade Name: Leflunomide
Product Name: Leflunomide
Pharmaceutical Form: Coated tablet
INN or Proposed INN: leflunomide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number
Sponsors
Ashford and St Peter's Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years 2. Patients with onset of symptoms ?15 days of onset 3. Laboratory (RT-PCR) confirmed infection with 2019-nCoV. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Pregnant or breast-feeding women; 2. Individuals already receiving specific antiviral medications (such as lopinavir/lidonavir, ribavirin), monoclonal antibodies, or other drug trial treatment for COVID-19 within one week prior to study enrolment; 3. Liver function tests>2 fold of upper limits of normal (ULN). Advisory: If the attending clinician considers that there exists a specific contra-indication to leflunomide (such as severe hypoproteinaemia, severe immunodeficiency) to Leflunomide, then the patient would be considered ineligible for the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The overall objective of the trial is to evaluate the efficacy and safety of oral leflunomide in COVID-19 patients with moderate to critical complications. The primary focus will be on clinical progression (speed of recovery and complications, i.e. time to clinical improvement, TTCI) and on kinetics of viral clearance. This means 1. how many days it takes for patient to make clinical improvement after treatment. 2. how quickly for the the virus to clear from infected patients. ;Secondary Objective: The secondary outcome measures are 1. Overall outcome measures (time to Hospital Discharge, All cause mortality, Duration of Intensive Care Stay) 2. Organ and multiorgan function: degree of acute Lung Injury , cardiac function, low blood pressure and acute kidney Injury 3. Physiological and biochemical markers include P/F ratio, i.e. arterial pO2 divided by the FIO2) and clinical bimolecular characterisation (biomarkers including high specificity CRP, ferritin, procalcitonin, troponin, BNP, creatinine and kidney biomarkers. 4. Cytokine profile including pro and anti-inflammatory cytokines (China only) 5. Exploratory outcome: Clinical predictors based on computer modelling and artificial intelligence data analysis [Time Frame: up to 28 days] 6. Adverse events due to Leflunomide therapy such as stress and strain on liver function;Primary end point(s): 1.Time to Clinical Improvement (TTCI) [Censored atDay 28] [ Time Frame: up to 28 days ] 2.Viral clearance by time to 2019-nCoV RT-PCR negativity and change in viral load in upper respiratory tract specimens TTCI is defined as the time (in days) from initiation of study treatment (active or placebo) until a decline of two categories from status at randomisation on a 7 category ordinal scale of clinical status which ranges from 1 (discharged) to 7 (death) as per WHO R&D Blueprint expert group. The 7-category ordinal scale include: 1. not hospitalised with resumption of normal activities;2. not hospitaliz | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall outcome measures (time to Hospital Discharge, All cause mortality, Duration of Intensive Care Stay. 2. Organ and multiorgan function: degree of Acute Lung Injury by Berlin definition, cardiac function, vasoplegia and Acute Kidney Injury by the KDIGO criteria including the need and duration of invasive and non-invasive ventilation, incidence of re-intubation, tracheostomy, CXR scores, echocardiography, inotropic/vasoactive support, need for RRT 3. Physiological (P/F ratio, i.e. arterial pO2 divided by the FIO2) and clinical bimolecular characterisation(biomarkers including high specificity CRP, ferritin, procalcitonin, troponin, BNP, creatinine and kidney biomarkers. 4. Cytokine profile including pro and anti-inflammatory cytokines (China only) 5. Exploratory outcome: Clinical predictors based on AI data analysis 6. Adverse events due to leflunomide therapy such as hepatotoxicity.;Timepoint(s) of evaluation of this end point: 28 days after initiation of treatment (a course of 10 days oral administrations) | — |
Countries
United Kingdom
Contacts
Public ContactSt Peter's Hospital
Freda Gomes
Outcome results
None listed