COVID-19 Infection MedDRA version: 20.0 Level: LLT Classification code 10051905 Term: Coronavirus infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: Favipiravir
Pharmaceutical Form:
INN or Proposed INN: Favipiravir
CAS Number: 259793-96-9
Product Name: Hydroxychloroquine
Pharmaceutical Form:
INN or Proposed INN: Hydroxychloroquine
Sponsors
Chelsea and Westminster Hospital NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: he participant may enter the study if the following apply: 1. Adult participants: Signed informed consent 2. New admission to hospital for period expected to last = 1 night 3. Suspected or confirmed COVID-19 infection Patients are suspected of COVID-19 infection if they have one of the following: · Influenza like illness (fever =37.8°C and at least one of the following respiratory symptoms, which must be of acute onset: persistent cough, hoarseness, nasal discharge or congestion, shortness of breath, sore throat, wheezing or sneezing). · Acute respiratory distress syndrome · Radiological evidence of pneumonia 4. For women to be eligible to enter and participate in the study they should be: of non-child-bearing - potential defined as either post-menopausal (12 months of spontaneous amenorrhea and = 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or, - or of child-bearing potential have a negative pregnancy test at screening and agrees to remain sexually abstinent or use a method of contraception with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 225
Exclusion criteria
Exclusion criteria: The participant may not enter the study if ANY of the following apply: 1. Pregnant or breast feeding, due to potential teratogenicity 2. Hepatic impairment – (AST or ALT > 3.5 x upper limit of normal) 3. Renal impairment – (eGFR 430ms in males or >450ms in females, calculated as per investigators discretion) 8. Presently enrolled in an interventional drug study or on hydroxychloroquine or azithromycin for other therapeutic reasons 9. Unable to take medication via the oral or nasogastric route 10. Immunocompromised patients (see Appendix C) 11. Known sensitivity to Azithromycin (or other macrolide drugs), Hydroxychloroquine, zinc or Favipiravir NB See Section 9.1 for dose reduction guidance for patients with eGFR <50ml/ minute
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether early intervention with either a combination of hydroxychloroquine, azithromycin and zinc or favipirivir improves time to significant improvement in clinical status.;Secondary Objective: To assess whether early intervention with Favipiravir or the combination of Hydroxychloroquine, Zinc and Azithromycin improves mortality in patients with COVID-19 infection To determine whether early intervention with Favipiravir or the combination of Hydroxychloroquine, Zinc and Azithromycin reduces resource utilisation in patients with COVID-19 infection To explore whether early intervention with Favipiravir or the combination of Hydroxychloroquine, Zinc and Azithromycin attenuates the excessive inflammatory cytokine response in patients with COVID-19 infection ;Primary end point(s): Time to clinical improvement (post randomisation) by two points on a seven-category ordinal scale or live discharge from the hospital, whichever comes first The seven-category ordinal scale: 1: Not hospitalised with resumption of normal activities 2: Not hospitalised, but unable to resume normal 3: Hospitalised, not requiring supplemental oxygen 4: Hospitalised, requiring supplemental oxygen 5: Hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation or both 6: Hospitalised, requiring ECMO (Extra-corporal membrane oxygenation), invasive mechanical ventilation or both 7: Death ;Timepoint(s) of evaluation of this end point: Data for assessment of primary endpoint will be collected until discharge from inpatient care, 28 day from enrolment or death. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Clinical status as assessed with the seven-category ordinal scale at day 7 and day 14 (post- randomisation)(19) 2. Change in clinical status as assessed with the seven-category ordinal scale at day 7 and day 14 (post- randomisation) relative to baseline(19) 3. All-cause in-hospital mortality 4. Time to clinical response defined as: Time to hospital discharge OR Time to NEWS2 (National Early Warning Score 2) of = 2, maintained for 24 hours(20) 5. Time to substantial clinical response as defined as: Time to hospital discharge or Time to NEWS2 (National Early Warning Score 2) of = 3, maintained for 24 hours(20) 6. Time to clinical response (temperature, heartrate, respiratory rate, oxygen saturations) 7. Number of participants requiring intensive care admission 8. Duration of intensive care admission 9. Number of participants requiring mechanical ventilation 10. Duration of mechanical ventilation 11. Number of participants requiring non-invasive ventilation, continuous positive airways pressure or high-flow oxygen via (Optiflo ®, Airvo system or equivalent) 12. Percentage of progression in supplemental oxygen requirement at day 7 13. Inflammatory serum makers at day 7 to 10, relative to baseline 14. Number of participants readmitted to hospital (all-cause) 15. Proportion of patients with bacterial or fungal infection 16. Changes in host cytokine profiles at post randomisation time points relative to baseline ;Timepoint(s) of evaluation of this end point: Data and samples will be collected from recruitment to discharge from inpatient care, 28 days from enrolment or death in order to assess the secondary endpoints. | — |
Countries
United Kingdom
Contacts
Public ContactResearch and Development Office
Chelsea and Westminster Hospital NHS Foundation Trust
Outcome results
None listed