Favipiravir and/or nitazoxanide: a randomized, double-blind, 2×2 design, placebo-controlled trial of early therapy in COVID-19 in health workers, their household members, and patients treated at IMSS (FANTAZE).
2×2 design
Antivirals
COVID-19
Combination therapy
Early treatment
Favipiravir
Nitazoxanide
Placebo-controlled trial
Protocol
Randomised controlled trial
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
22 Jul 2022
22 Jul 2022
Historique:
received:
28
02
2022
accepted:
08
07
2022
entrez:
22
7
2022
pubmed:
23
7
2022
medline:
27
7
2022
Statut:
epublish
Résumé
The 2020 pandemic of SARS-CoV-2 causing COVID-19 disease is an unprecedented global emergency. COVID-19 appears to be a disease with an early phase where the virus replicates, coinciding with the first presentation of symptoms, followed by a later 'inflammatory' phase which results in severe disease in some individuals. It is known from other rapidly progressive infections such as sepsis and influenza that early treatment with antimicrobials is associated with a better outcome. The hypothesis is that this holds for COVID-19 and that early antiviral treatment may prevent progression to the later phase of the disease. Trial design: Phase IIA randomised, double-blind, 2 × 2 design, placebo-controlled, interventional trial. Participants will be randomised 1:1 by stratification, with the following factors: gender, obesity, symptomatic or asymptomatic, current smoking status presence or absence of comorbidity, and if the participant has or has not been vaccinated. Participants and investigators will both be blinded to treatment allocation (double-blind). We propose to conduct a proof-of-principle placebo-controlled clinical trial of favipiravir plus or minus nitazoxanide in health workers, their household members and patients treated at the Mexican Social Security Institute (IMSS) facilities. Participants with or without symptomatic COVID-19 or who tested positive will be assigned to receive favipiravir plus nitazoxanide or favipiravir plus nitazoxanide placebo. The primary outcome will be the difference in the amount of virus ('viral load') in the upper respiratory tract after 5 days of therapy. Secondary outcomes will include hospitalization, major morbidity and mortality, pharmacokinetics, and impact of antiviral therapy on viral genetic mutation rate. If favipiravir with nitazoxanide demonstrates important antiviral effects without significant toxicity, there will be a strong case for a larger trial in people at high risk of hospitalization or intensive care admission, for example older patients and/or those with comorbidities and with early disease. ClinicalTrials.gov NCT04918927 . Registered on June 9, 2021.
Sections du résumé
BACKGROUND
BACKGROUND
The 2020 pandemic of SARS-CoV-2 causing COVID-19 disease is an unprecedented global emergency. COVID-19 appears to be a disease with an early phase where the virus replicates, coinciding with the first presentation of symptoms, followed by a later 'inflammatory' phase which results in severe disease in some individuals. It is known from other rapidly progressive infections such as sepsis and influenza that early treatment with antimicrobials is associated with a better outcome. The hypothesis is that this holds for COVID-19 and that early antiviral treatment may prevent progression to the later phase of the disease.
METHODS
METHODS
Trial design: Phase IIA randomised, double-blind, 2 × 2 design, placebo-controlled, interventional trial.
RANDOMISATION
METHODS
Participants will be randomised 1:1 by stratification, with the following factors: gender, obesity, symptomatic or asymptomatic, current smoking status presence or absence of comorbidity, and if the participant has or has not been vaccinated.
BLINDING
METHODS
Participants and investigators will both be blinded to treatment allocation (double-blind).
DISCUSSION
CONCLUSIONS
We propose to conduct a proof-of-principle placebo-controlled clinical trial of favipiravir plus or minus nitazoxanide in health workers, their household members and patients treated at the Mexican Social Security Institute (IMSS) facilities. Participants with or without symptomatic COVID-19 or who tested positive will be assigned to receive favipiravir plus nitazoxanide or favipiravir plus nitazoxanide placebo. The primary outcome will be the difference in the amount of virus ('viral load') in the upper respiratory tract after 5 days of therapy. Secondary outcomes will include hospitalization, major morbidity and mortality, pharmacokinetics, and impact of antiviral therapy on viral genetic mutation rate. If favipiravir with nitazoxanide demonstrates important antiviral effects without significant toxicity, there will be a strong case for a larger trial in people at high risk of hospitalization or intensive care admission, for example older patients and/or those with comorbidities and with early disease.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov NCT04918927 . Registered on June 9, 2021.
Identifiants
pubmed: 35869526
doi: 10.1186/s13063-022-06533-0
pii: 10.1186/s13063-022-06533-0
pmc: PMC9306230
doi:
Substances chimiques
Amides
0
Antiviral Agents
0
Nitro Compounds
0
Pyrazines
0
Thiazoles
0
favipiravir
EW5GL2X7E0
nitazoxanide
SOA12P041N
Banques de données
ClinicalTrials.gov
['NCT04918927']
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
583Subventions
Organisme : Medical Research Council
ID : MR/M008665/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/W015560/1
Pays : United Kingdom
Organisme : Fundación IMSS
ID : Not applicable
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
Références
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