Early Intervention in COVID-19: Favipiravir Verses Standard Care

Study Overview
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Brief Summary
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Currently we do not know how best to treat patients infected with COVID-19. This study is looking at whether randomising participants to either favipiravir or to usual care, can help patients with suspected or proven COVID-19 infection.

Detailed Description
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A prospective, randomised, open label study of the combined use of favipiravir and standard clinical care verses standard clinical care alone. A computer-based software will randomise participants 1:1 to either receive favipiravir and standard medical care or standard medical care alone. The allocated medical regime will commence for 10 days. Research blood, sputum nose swab and urine samples will be collected at baseline, as well as between day 5 and 10, and between day 14 and 28 to enable comparative analyses. A COVID-19 antibody test will also be performed 14-28 days after randomisation. In the event of clinically indicated bronchoscopy taking place within 28 days of consent then additional bronchoscopy washing and brushing samples and paired blood sample will be taken for research purposes If a participant is discharged before one of the latter time points, they will be required to return to hospital (provided they are well enough) for the collection of repeat samples. Participants will be closely monitored whilst taking the study medications. Participants will study exit at subject death or 28 days post-randomisation.

Official Title
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A Randomised Controlled Trial of Early Intervention in Patients HospItalised With COVID-19: Favipiravir and StaNdard Care vErsEs Standard CaRe

Conditions
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Coronavirus Infection

Intervention / Treatment
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* Drug: Favipiravir
* Other: Standard of care management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult participants: Signed informed consent New admission to hospital for period expected to last ≥ 1 night Suspected or confirmed COVID-19 infection Patients are suspected of COVID-19 infection if they have 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). And · Finding from either a chest x-ray or CT suggestive of Covid-19 infection And · Alternative causes are considered unlikely 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 < 1% per year as indicated in Appendix B during the treatment and for a period of 7 days after the last dose. Hormonal contraceptive methods must be supplemented by a barrier method. Men who are sexually active must use an adequate method of contraception as listed in Appendix B, for a period of at least 7 days after the last dose Exclusion Criteria: Pregnant or breast feeding, due to potential teratogenicity Hepatic impairment - (AST or ALT > 3.5 x upper limit of normal) Presently enrolled in an interventional drug study Unable to take medication via the oral or nasogastric route Known sensitivity Favipiravir

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label parallel group randomised control trial. One trial treatment arm and one standard of care comparator arm.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Favipiravir & Standard of Care<br>Favipiravir: Day 1 1800mg twice per day, Days 2-10 800mg twice per day | Drug: Favipiravir<br>* Anti-viral<br>* Other names: Avigan;Other: Standard of care management<br>* Standard of care management for COVID-19<br>|
| Other: Standard of care<br>No trial intervention | Other: Standard of care management<br>* Standard of care management for COVID-19<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from randomisation to a sustained clinical improvement (maintained for 24 hours) by two points on a seven-category ordinal scale or to discharge, whichever occurs first | Time from randomisation to a sustained clinical improvement (maintained for 24 hours) by two points on a seven-category ordinal scale or to discharge, whichever occurs first The seven-category ordinal scale is : Not hospitalised with resumption of normal activities Not hospitalised, but unable to resume normal Hospitalised, not requiring supplemental oxygen Hospitalised, requiring supplemental oxygen Hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation or both Hospitalised, requiring ECMO (Extra-corporal membrane oxygenation), invasive mechanical ventilation or both Death | Up to 28 days from randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical status on a seven-category ordinal scale (Day 7) | Clinical status of patients at given on the seven-category ordinal scale (see primary endpoint for scale) | Day 7 from randomisation | 
| Clinical status on a seven-category ordinal scale (Day 14) | Clinical status of patients at given on the seven-category ordinal scale (see primary endpoint for scale) | Day 14 from randomisation | 
| Overall survival | Survival of patients to end of study | 28 days from randomisation | 
| Time to improvement by two points on the NEWS score | Time from randomisation to improvement by two points on the NEWS score of patient condition, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2 | Up to 28 days from randomisation | 
| Time to improvement by two points on the NEWS element score for temperature | Time from randomisation to improvement by two points on the NEWS element score for temperature, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2 | Up to 28 days from randomisation | 
| Time to improvement by two points on the NEWS element score for heartrate | Time from randomisation to improvement by two points on the NEWS element score for heartrate, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2 | Up to 28 days from randomisation | 
| Time to improvement by two points on the NEWS element score for respiratory rate | Time from randomisation to improvement by two points on the NEWS element score for respiratory rate, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2 | Up to 28 days from randomisation | 
| Time to improvement by two points on the NEWS element score for oxygen saturation. | Time from randomisation to improvement by two points on the NEWS element score for oxygen saturation, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2 | Up to 28 days from randomisation | 
| Admission to intensive care | Frequency of admission of patients to intensive care | Up to 28 days from randomisation | 
| Requirement for mechanical ventilation | Frequency of requirement to administer mechanical ventilation to patients | Up to 28 days from randomisation | 
| Requirement for non-invasive ventilation, continuous positive airways pressure or high-flow oxygen | Frequency of requirement to administer non-invasive ventilation, continuous positive airways pressure or high-flow oxygen to patients | Up to 28 days from randomisation | 
| Incidence of bacterial or fungal infection | Frequency of culture-confirmed bacterial or fungal infection in patients | Up to 28 days from randomisation | 
| Incidence of adverse events not directly caused by COVID-19 infection. | Frequency and severity of adverse events in patients not directly attributed by clinicians to COVID-19 infection. | Up to 28 days from randomisation. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Coronavirus