text: Glasgow Early Treatment Arm Favirpiravir GETAFIX for adults with early stage COVID 19 A structured summary of a study protocol for a randomised controlled trial The GETAFIX trial will test the hypothesis that favipiravir is a more effective treatment for COVID 19 infection in patients who have early stage disease compared to current standard of care This study will also provide an important opportunity to investigate the safety and tolerability of favipiravir the pharmacokinetic and pharmacodynamic profile of this drug and mechanisms of resistance in the context of COVID 19 infection as well as the effect of favipiravir on hospitalisation duration and the post COVID 19 health and psycho social wellbeing of patients recruited to the study GETAFIX is an open label parallel group two arm phase II III randomised trial with 1 1 treatment allocation ratio Patients will be randomised to one of two arms and the primary endpoint will assess the superiority of favipiravir plus standard treatment compared to standard treatment alone This trial will recruit adult patients with confirmed positive valid COVID 19 test who are not pregnant or breastfeeding and have no prior major co morbidities This is a multi centre trial patients will be recruited from in patients and outpatients from three Glasgow hospitals Royal Alexandra Hospital Queen Elizabeth University Hospital and the Glasgow Royal Infirmary Patients must meet all of the following criteria 1 Age 16 or over at time of consent 2 Exhibiting symptoms associated with COVID 19 3 Positive for SARS CoV 2 on valid COVID 19 test 4 Point 1 2 3 or 4 on the WHO COVID 19 ordinal severity scale at time of randomisation Asymptomatic with positive valid COVID 19 test Symptomatic Independent Symptomatic assistance needed Hospitalized with no oxygen therapy 5 Have 10 risk of death should they be admitted to hospital as defined by the ISARIC4C risk index https isaric4c net risk 6 Able to provide written informed consent 7 Negative pregnancy test women of childbearing potential 8 Able to swallow oral medication Patients will be excluded from the trial if they meet any of the following criteria 1 Renal impairment requiring or likely to require dialysis or haemofiltration 2 Pregnant or breastfeeding 3 Of child bearing potential women or with female partners of child bearing potential men who do not agree to use adequate contraceptive measures for the duration of the study and for 3 months after the completion of study treatment 4 History of hereditary xanthinuria 5 Other patients judged unsuitable by the Principal Investigator or sub Investigator 6 Known hypersensitivity to favipiravir its metabolites or any excipients 7 Severe co morbidities including patients with severe hepatic impairment defined as greater than Child Pugh grade A AST or ALT 5 x ULN AST or ALT 3 x ULN and Total Bilirubin 2xULN 8 More than 96 hours since first positive COVID 19 test sample was taken 9 Unable to discontinue contra indicated concomitant medications This is a multi centre trial patients will be recruited from in patients and outpatients from three Glasgow hospitals Royal Alexandra Hospital Queen Elizabeth University Hospital and the Glasgow Royal Infirmary Patients randomised to the experimental arm of GETAFIX will receive standard treatment for COVID 19 at the discretion of the treating clinician plus favipiravir These patients will receive a loading dose of favipiravir on day 1 of 3600mg 1800mg 12 hours apart On days 2 10 patients in the experimental arm will receive a maintenance dose of favipiravir of 800mg 12 hours apart total of 18 doses Patients randomised to the control arm of the GETAFIX trial will receive standard treatment for COVID 19 at the discretion of the treating clinician The primary outcome being assessed in the GETAFIX trial is the efficacy of favipiravir in addition to standard treatment in patients with COVID 19 in reducing the severity of disease compared to standard treatment alone Disease severity will be assessed using WHO COVID 10 point ordinal severity scale at day 15 48 hours All randomised participants will be followed up until death or 60 days post randomisation whichever is sooner Patients will be randomised 1 1 to the experimental versus control arm using computer generated random sequence allocation A minimisation algorithm incorporating a random component will be used to allocate patients The factors used in the minimisation will be site age 16 50 51 70 71 history of hypertension or currently obsess BMI 30 or obesity clinically evident yes no 7 days duration of symptoms yes no unknown sex male female WHO COVID 19 ordinal severity score at baseline 1 2or 3 4 No blinding will be used in the GETAFIX trial Both participants and those assessing outcomes will be aware of treatment allocation In total 302 patients will be randomised to the GETAFIX trial 151 to the control arm and 151 to the experimental arm There will be an optional consent form for patients who may want to contribute to more frequent PK and PD sampling The maximum number of patients who will undergo this testing will be sixteen eight males and eight females This option will be offered to all patients who are being treated in hospital at the time of taking informed consent however only patients in the experimental arm of the trial will be able to undergo this testing The current GETAFIX protocol is version 4 0 12 sup th sup September 2020 GETAFIX opened to recruitment on 26 sup th sup October 2020 and will recruit patients over a period of approximately six months GETAFIX was registered on the European Union Drug Regulating Authorities Clinical Trials EudraCT Database on 15 sup th sup April 2020 Reference number 2020 001904 41 https www clinicaltrialsregister eu ctr search trial 2020 001904 41 GB GETAFIX was registered on ISRCTN on 7 sup th sup September 2020 Reference number ISRCTN31062548 https www isrctn com ISRCTN31062548 The full protocol is attached as an additional file accessible from the Trials website Additional file 1 In the interest in expediting dissemination of this material the familiar formatting has been eliminated this Letter serves as a summary of the key elements of the full protocol The study protocol has been reported in accordance with the Standard Protocol Items Recommendations for Clinical Interventional Trials SPIRIT guidelines see Additional file 2 