Early antiviral treatment in outpatients with COVID-19 : a structured summary of a study protocol for a randomised controlled trial

Objectives The objective of this trial is to assess whether early antiviral therapy in outpatients with COVID-19 with either favipiravir plus lopinavir/ritonavir, lopinavir/ritonavir alone, or favipiravir alone, is associated with a decrease in viral load of SARS-CoV-2 compared with placebo. Trial design FLARE is a phase IIA randomised, double-blind, 2x2 factorial placebo-controlled, interventional trial. Participants This trial is being conducted in the United Kingdom, with Royal Free Hospital, London as the lead site. Participants are non-hospitalised adults with highly suspected COVID-19 within the first 5 days of symptom onset, or who have tested positive with SARS-CoV-2 causing COVID-19 within the first 7 days of symptom onset, or who are asymptomatic but tested positive for SARS-CoV-2 for the first time within the last 48 hours. Inclusion criteria are as follows: Any adult with the following: Symptoms compatible with COVID-19 disease (Fever >37.8[degrees]C on at least one occasion AND either cough and/ or anosmia) within the first 5 days of symptom onset (date/time of enrolment must be within the first 5 days of symptom onset) OR ANY symptoms compatible with COVID-19 disease (may include, but are not limited to fever, cough, shortness of breath, malaise, myalgia, headache, coryza) and tested positive for SARS-CoV-2 within the first 7 days of symptom onset) (date/time of enrolment must be within the first 7 days of symptom onset) OR no symptoms but tested positive for SARS-CoV-2 within the last 48 hours (date/time of test must be within 48 hours of enrolment) Male or female aged 18 years to 70 years old inclusive at screening Willing and able to take daily saliva samples Able to provide full informed consent and willing to comply with trial-related procedures Exclusion criteria are as follows: Known hypersensitivity to any of the active ingredients or excipients in favipiravir and matched placebo, and in lopinavir/ritonavir and matched placebo (See Appendix 2) Chronic liver disease at screening (known cirrhosis of any aetiology, chronic hepatitis (e.g. autoimmune, viral, steatohepatitis), cholangitis or any known elevation of liver aminotransferases with AST or ALT > 3 X ULN)* Chronic kidney disease (stage 3 or beyond) at screening: eGFR < 60 ml/min/1.73m.sup.2 * HIV infection, if untreated, detectable viral load or on protease inhibitor therapy Any clinical condition which the investigator considers would make the participant unsuitable for the trial