TY - JOUR
T1 - Favipiravir and/or nitazoxanide
T2 - 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)
AU - Smith, Tania
AU - Hoyo-Vadillo, Carlos
AU - Adom, Akosua Agyeman
AU - Favari-Perozzi, Liliana
AU - Gastine, Silke
AU - Dehbi, Hakim Moulay
AU - Villegas-Lara, Beatriz
AU - Mateos, Eduardo
AU - González, Yessica Sara Pérez
AU - Navarro-Gualito, Maria D.
AU - Cruz-Carbajal, Alejandra S.
AU - Cortes-Vazquez, Miguel A.
AU - Bekker-Méndez, Carolina
AU - Aguirre-Alvarado, Charmina
AU - Aguirre-Gil, Gisela
AU - Delgado-Pastelin, Lucero
AU - Owen, Andrew
AU - Lowe, David
AU - Standing, Joseph
AU - Escobedo, Jorge
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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: Trial design: Phase IIA randomised, double-blind, 2 × 2 design, placebo-controlled, interventional trial. Randomisation: 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: Participants and investigators will both be blinded to treatment allocation (double-blind). Discussion: 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: ClinicalTrials.govNCT04918927. Registered on June 9, 2021.
AB - 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: Trial design: Phase IIA randomised, double-blind, 2 × 2 design, placebo-controlled, interventional trial. Randomisation: 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: Participants and investigators will both be blinded to treatment allocation (double-blind). Discussion: 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: ClinicalTrials.govNCT04918927. Registered on June 9, 2021.
KW - 2×2 design
KW - Antivirals
KW - COVID-19
KW - Combination therapy
KW - Early treatment
KW - Favipiravir
KW - Nitazoxanide
KW - Placebo-controlled trial
KW - Protocol
KW - Randomised controlled trial
UR - http://www.scopus.com/inward/record.url?scp=85134612555&partnerID=8YFLogxK
U2 - 10.1186/s13063-022-06533-0
DO - 10.1186/s13063-022-06533-0
M3 - Artículo
C2 - 35869526
AN - SCOPUS:85134612555
SN - 1745-6215
VL - 23
JO - Trials
JF - Trials
IS - 1
M1 - 583
ER -