Condition category
Respiratory
Date applied
28/08/2020
Date assigned
07/09/2020
Last edited
24/09/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
COVID-19 is a new illness which can affect different parts of the body including the lungs and airways. The purpose of this study is to see if giving patients who have milder symptoms of COVID-19 (not requiring oxygen support) a drug called favipiravir will help with their symptoms and reduce the time it takes to recover. We are targeting patients who are at higher risk of going on to develop more severe COVID-19. Around 300 patients will take part in the study, and half will be given the drug along with the normal standard treatment, and the other half will receive normal standard treatment alone. We can then compare the two groups to see if the drug has a positive effect and if it may be useful in treating future patients with COVID-19.

Who can participate?
Adults aged 16 or over who have symptoms of COVID-19 and a positive COVID-19 test result. Participants should be in a higher risk category for severe disease according to the ISARIC4C risk index, as assessed by the treating doctor. Patients requiring oxygen therapy will not be included. All participants must be able to provide written informed consent, and be able to swallow tablets. The following are excluded: Pregnant or breast-feeding women, kidney disease requiring (or likely to require) dialysis or haemofiltration, history of hereditary xanthinuria, known allergy to the study drug or any ingredients, severe liver disease. Female participants of child-bearing potential should not become pregnant within 3 months of completing the course of study drug.

What does the study involve?
After informed consent has been given, patients will undergo screening tests to check they are suitable for the study. This will involve :
1. Routine clinical observations (temperature, pulse rate, oxygen saturation, blood pressure, breathing rate)
2. Height and Weight
3. Routine clinical blood tests
4. Pregnancy test (for people of childbearing potential)
5. Nose and throat swab to test for coronavirus (if not performed already)
6. Patients unable to return for a day 1 visit will also have blood samples for research purposes taken

Once confirmed as eligible, patients will be randomly allocated either recieve standard care alone, or standard care and favipiravir – this will be decided randomly using a computer program. Patients receiving favipiravir will take the drug twice daily: 9 tablets 12 hours apart on the first day, and 4 tablets 12 hours apart on days 2-10. The tablet strength is 200mg, and the tablets are round, coated and about 9mm in diameter.

Patients will be assessed daily (a daily telephone call for outpatients) and any symptoms noted. Patients who are in hospital will also have clinical observations performed daily, and blood tests on days 1, 3, and 8. All patients will have follow up assessments on days 15, 29, and 60, where all the tests at screening will be repeated. Patients will also be asked to fill out a questionnaire about their health and wellbeing at these visits.

What are the possible benefits and risks of participating?
It is possible that favipiravir may help to reduce the symptoms of COVID-19 or reduce the time taken to recover. Even if patients do not benefit directly, information from this study will help improve our understanding of using favipiravir to treat COVID-19 for future patients.

Potential side effects of the treatment being used in the trial, and the percentage of people who experienced them, are summarised in the Patient Information Sheet. Patients taking favipiravir will be contacted daily by the study team while taking the drug, and if at any time the patient or their doctor felt the side effects were a problem, the drug would be stopped.

Where is the study run from?
The study is being co-ordinated by the Cancer Research UK Clinical Trials Unit in Glasgow. The study has no link to cancer, but the trials unit had the necessary resource and experience to run the trial, and CRUK were supportive of diverting resource to COVID-19 research during this time of need.

When is the study starting and how long is it expected to run for?
From May 2020 to May 2021

Who is funding the study?
Scottish Government Chief Scientist Office (CSO)

Who is the main contact?
1. Professor Rob Jones
2. Mrs Carol Evans
carol.evans@glasgow.ac.uk
3. Laura Divers
laura.divers@glasgow.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Carol Evans

ORCID ID

Contact details

Research & Development
Ward 11
Dykebar Hospital
Grahamston
Glasgow
PA2 7DE
United Kingdom
+44 (0)141 301 7189
carol.evans@glasgow.ac.uk

Additional identifiers

EudraCT number

2020-001904-41

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 46289, IRAS 283151

Study information

Scientific title

Glasgow Early Treatment Arm FavIpiravir: A randomized controlled study of favipiravir as an early treatment arm in COVID-19 patients

Acronym

GETAFIX

Study hypothesis

Favipiravir may be a more effective treatment for COVID 19 infection, compared to the current standard treatment of supportive care

Ethics approval

Approved 20/05/2020, West of Scotland Research Ethics Committee 1 (Ward 11, Dykebar Hospital, Grahamston Road, Paisley PA2 7DE; +44 (0)141 314 0212; WoSRec1@ggc.scot.nhs.uk), ref: 20/WS/0073

Study design

Single centre, open-label randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

See additional files ISRCTN31062548_PIS_outpatients_v1.0_14Jul2020 (outpatients) and ISRCTN31062548_PIS_inpatients_v1.0_14Jul2020 (inpatients)

Condition

COVID-19 (SARS-CoV-2 infection)

Intervention

On admission to the study (baseline) the following will be collected from patients:
1. Written informed consent
2. Assessment of eligibility criteria
3. Demographic details
4. Nasopharyngeal swab (a swab taken from the nose used for COVID-19 PCR assessment which gives either “postitive or negative” results, and is also used to measure the viral load which tells us how much virus a patient has)
5. Medical history including assessment of medical co-morbidities and suitability for potential entry to ICU
6. Documentation of other medications the patient is taking
7. Clinical examination
8. Human chorionic gonadotrophin (HCG) test to rule out pregnancy at trial entry. Results must be obtained and reviewed before randomisation for people of childbearing potential
9. Routine observations of respiratory rate, percentage of Oxygen in the blood, Blood pressure, and temperature, to gauge the current state of health
10. Routine clinical blood tests which will include those required to assess eligibility (full blood count, urea and electrolytes, renal function: creatinine and eGFR, liver function tests, c-reactive protein and an assessment of clotting)
11. Height and weight to assess the current state of health, by calculation of a BMI which is required for eligibility, and to help understand the distribution of the drug in people of different sizes
12. Pre-morbid performance status as assessed by WHO criteria to give a longer term indication of the state of health
13. WHO COVID 10 point ordinal severity scale assessment to measures the current severity of COVID-19

Patients will be allocated to either standard care alone (control arm) or standard care + favipiravir (intervention arm) on a 1:1 basis using a minimisation algorithm incorporating a random component. Factors used in the minimisation will be:
1. Age (16 - 50; >50 – 70; >70)
2. <7 days duration of symptoms (yes; no; unknown)
3. Sex (male; female)
4. History of hypertension or currently obese (BMI >30 or obesity clinically evident)
6. COVID ordinal severity score at baseline (2/3; 4)
7. Treating Hospital

Patients receiving favipiravir will take the drug twice daily: 9 tablets, 12 hours apart on the first day, and 4 tablets, 12 hours apart on days 2-10. The tablet strength is 200mg, and the tablets are round, coated and about 9mm in diameter. The following will be assessed on days 1 to 10 unless indicated otherwise:
1. WHO COVID 10 point ordinal severity scale assessment (taken as the worst value on the previous day)
2. Documentation of concomitant medications
3. Assessment of adverse events
4. Routine clinical blood tests (as above)
5. Routine observations/vital signs (as above)
6. Routine clinical blood tests and blood tests for immunological and epigenetic testing on days 1, 3, 8, and 11 (as above)
7. Symptom directed clinical examination if clinically indicated
8. Nasopharyngeal swab (for COVID-19 SARS-CoV-2 PCR assessment and Viral Load) on days 1 (at time of first dose), 3, 7, 10, 13, and on discharge if before 15 days.
9. Pharmacokinetic samples according to the sample schedule to ascertain the concentration of blood circulating in the patient. Performed by The Pharmacy Department Uni of Strathclyde and Translational
Pharmacology Lab, Uni of Glasgow.

For patients in the community or discharged from hospital before 14 days, telephone assessment of the WHO COVID 10 point ordinal severity scale assessment, concomitant medication, and adverse events, will be undertaken by an investigator with the patient.

Follow up will take place at 15, 29, and 60 days where the following will be assessed:
1. WHO COVID 10 point ordinal severity scale assessment
2. Blood tests for immunological and epigenetic testing and routine clinical blood tests
3. Telephone or in person assessment of concomitant medication and adverse events
4. Nasopharyngeal swab (for SARS-CoV-2 PCR assessment and viral load)
5. The COVID-19 Health and Wellbeing follow up survey

Records will also be kept of survival, duration of hospitalisation, and duration of pyrexia.

Intervention type

Drug

Phase

Phase II

Drug names

Favipiravir

Primary outcome measure

Efficacy of favipiravir in addition to standard care in patients with COVID-19 in reducing the severity of disease compared to standard care alone measured using
the WHO COVID 10 point ordinal scale at 15 days

Secondary outcome measures

1. Effect of favipiravir in addition to standard care in the study population compared to standard care alone measured using:
1.1. The WHO COVID 10 point ordinal scale, measured at baseline, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 29, and 60 days (measurements on days 1-10 by telephone in outpatients)
1.2. Viral Clearance measured from nasopharyngeal swabs at baseline and 8 days
1.3. Overall survival, assessed up to and including 60 days
1.4. Duration of pyrexia by temperature measured in inpatients only, up to and including the day of discharge or 60 days
2. Safety and tolerability of favipiravir in the study population measured by assessment of adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) v5 at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 29, and 60 days (measurements on days 1-10 by telephone in outpatients)
3. Effect of favipiravir on the duration of hospitalisation measured by assessment of patient status up to and including 60 days
4. Pharmacokinetics of favipiravir measured by blood sampling at baseline and 1 days (outpatients), or baseline, 1, 3, 5, 8 and 10 days (inpatients)
5. Mechanisms of resistance, immunological and biometric markers contributing to clinical conditions in COVID-19 patients measured by blood sampling at baseline (screening), 15, 29, and 60 days (outpatients), or baseline (day 1) and 3, 15, 29, and 60 days (inpatients)
6. Post COVID-19 health and psycho-social consequences measured by the COVID-19 Health and Wellbeing follow up survey at 15, 29, and 60 days

Overall trial start date

01/04/2020

Overall trial end date

31/12/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged ≥16 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 the time of randomisation (asymptomatic with positive valid COVID19 test, symptomatic independent, symptomatic assistance needed, or 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 if participant is of childbearing potential
8. Able to swallow oral medication

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 302; UK Sample Size: 302

Participant exclusion criteria

1. Renal impairment requiring, or likely to require, dialysis or haemofiltration
2. Pregnant or breastfeeding
3. Child bearing potential, or, with partners of child bearing potential, who do not agree to the 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. Judged to be ineligible by the principal investigator or sub-investigator
6. Known hypersensitivity to favipiravir, its metabolites, or its 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, or AST or ALT >3 x ULN and Total Bilirubin >2 x ULN
8. >96 h since first positive COVID19 test sample was taken
9. Unable to discontinue contra-indicated concomitant medications

Recruitment start date

14/09/2020

Recruitment end date

31/12/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

NHS Greater Glasgow and Clyde
J B Russell House Gartnavel Royal Hospital 1055 Great Western Road
Glasgow
G12 0XH
United Kingdom

Sponsor information

Organisation

NHS Greater Glasgow and Clyde

Sponsor details

Research & Development
Ward 11
Dykebar Hospital
Grahamston
Glasgow
PA2 7DE
United Kingdom
+44 (0)1413144001
joanne.mcgarry@ggc.scot.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.nhsggc.org.uk/

Funders

Funder type

Government

Funder name

Chief Scientist Office, Scottish Government Health and Social Care Directorate

Alternative name(s)

Funding Body Type

government organisation

Funding Body Subtype

Local government

Location

United Kingdom

Funder name

National Institute for Health Research (NIHR) (UK)

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal. The study protocol will also be submitted for publication.

IPD sharing statement:
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication

Intention to publish date

31/12/2021

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

28/08/2020: Trial’s existence confirmed by the National Institute for Health Research (NIHR).