GETAFIX
Research type
Research Study
Full title
Glasgow Early Treatment Arm FavIpiravir : A randomized controlled study of favipiravir as an early treatment arm in COVID-19 patients
IRAS ID
283151
Contact name
Joanne McGarry
Contact email
Sponsor organisation
NHS Greater Glasgow & Clyde
Eudract number
2020-001904-41
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Research Summary
There is a current global pandemic of COVID 19 infection caused by a novel virus. As of 12th April 2020 there were 78 995 confirmed cases in the UK, and 9875 deaths since the beginning of 2020. Globally the number of confirmed cases stood at 1, 696 588 with 105 952 deaths. Currently there is no specific treatment approved for use against COVID 19 and patients are treated with symptom directed supportive measures only, such as oxygen therapy. Therefore, there is an urgent need to develop and test agents that help to reduce the transmission, morbidity and death rate attributable to COVID 19.
Favipiravir is an antiviral agent used against severe influenza and it has been used in trials against other viruses with promising results. There is a strong rationale for testing favipiravir against COVID 19 and there is an urgent need to do so in a controlled, clinical trial setting.
The working hypothesis for the GETAFIX trial is that Favipiravir may be a more effective treatment for COVID 19 infection for those patients who require hospitalisation, compared to current standard treatment of supportive care. This hypothesis will be tested by evaluating the difference in severity of disease at day 14 as the trial primary endpoint. This study will provide an important opportunity to evaluate Favipiravir’s properties, such as the effective dose and duration of action, in COVID 19 infected patients. The trial will also include an evaluation of potential mechanisms of resistance of COVID 19 to this drug. If successful at meeting its primary endpoint, the GETAFIX trial has the potential to be highly impactful if Favipiravir is considered for use globally to treat COVID19 to reduce deaths, admissions to ICU and transmission of SARS-CoV2.
Summary of Results
KEY FINDINGS • Between December 2020 and July 2022, 68,788 adults were invited. 302 (0.4%) were subsequently randomised to receive favipiravir (n=152) or no additional treatment (n=150).
• The average age of patients recruited was 47 years old. 230/302 (76.2%) were vaccinated.
• Severe outcomes were infrequent, with no ICU admissions or deaths.
• We did not observe any clinical effect from taking favipiravir. This was measured by the distribution of disease outcomes up to 15 days after randomisation.
• The was also no difference in the time taken for symptoms to resolve or the time for virus to be cleared from nasal swab samples.
• Favipiravir was well tolerated with no safety concerns. Although we observed evidence of favipiravir-induced SARS-CoV-2 virus mutation, the mutations identified were not of clinical relevance.
WHAT WERE THE RESULTS AND WHAT DO THEY MEAN?
Despite initiating therapy promptly, we observed no clinical benefits. The incidence of severe COVID-19 disease was much lower than expected in both arms of our trial, with no ICU admissions, no deaths and only 5 hospitalisations. This probably reflected the fact that most patients were young (mean age 47) and fit (64.9% reported no comorbidity), and the population had a high rate of prior COVID-19 vaccination (76.2%). Favipiravir was well-tolerated and safe.We observed no difference in time to symptom resolution or time to viral clearance, although our data regarding viral clearance are based on limited numbers of repeat samples. SARS-CoV-2 viral genomic sequencing identified evidence of favipiravir-induced mutagenesis, including an increase in C-to-U variants consistent with the known action of the drug. The mutations identified were not of known clinical relevance but support a cautious approach to use of favipiravir in COVID-19.
WHAT IMPACT COULD THE FINDINGS HAVE?
Prior to the current trial, favipiravir had been associated with potential clinical benefits in early treatment of COVID-19. In Japan it has been used extensively for this purpose. Our findings, which are concordant with results from other recent trials, suggest the drug is not effective.
The current trial was successful in reaching and initiating therapy quickly in community cases. This required development of novel methods for raising trial awareness, case identification and screening. Live public health data was used to maximise study reach, comprising 83,096 positive tests. However, most potentially eligible adults (66,464/68,788, 96.6%) did not respond to email invitations or other means of study advertising, including print, radio and social media. Of those who did respond, 302/2,324 (12.9%) were subsequently randomised following pre-screening +/- formal screening. This attrition reflects the difficulties involved in delivering trials of this nature and suggests more efficient methods are needed for future trials of early intervention for SARS-CoV-2 infection.
CONCLUSION
We observed no clinical benefits associated with favipiravir administration in mild COVID-19 in a well-vaccinated UK population with limited comorbidity. Favipiravir was well tolerated but was associated with evidence of new mutations in the SARS-CoV-2 virus.REC name
West of Scotland REC 1
REC reference
20/WS/0073
Date of REC Opinion
20 May 2020
REC opinion
Further Information Favourable Opinion