Back to resultsFavipiravir +/- Nitazoxanide: Early Antivirals Combination Therapy in COVID-19 (FANTAZE)
Primary Purpose
Covid19
Status
Completed
Phase
Phase 2
Locations
Mexico
Study Type
Interventional
Intervention
Favipiravir
Nitazoxanide
Nitazoxanide Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Covid19
Eligibility Criteria
Inclusion Criteria:
Health workers, their household members and, IMSS beneficiaries with the following:
- Symptoms compatible with COVID-19 disease (Fever >37.8oC on at least one occasion AND either cough and/ or anosmia) within the first 5 days of symptom onset (date/time of enrolment must be within the first 5 days of symptom onset)
- OR ANY symptoms compatible with COVID-19 disease (may include, but are not limited to fever, cough, shortness of breath, malaise, myalgia, headache, coryza) and tested positive for SARS-CoV-2 within the first 7 days of symptom onset (date/time of enrolment must be within the first 7 days of symptom onset)
- OR no symptoms but tested positive for SARS-CoV-2 within the last 48 hours (date/time of test must be within 48 hours of enrolment)
- Male or female aged 18 years to 70 years old inclusive at screening
- Willing and able to take daily saliva samples
- Able to provide full informed consent and willing to comply with trial-related procedures
Exclusion Criteria:
- Known hypersensitivity to any of the active ingredients or excipients in favipiravir, and in nitazoxanide and matched placebo
- Chronic liver disease at screening (known cirrhosis of any aetiology, chronic hepatitis (e.g. autoimmune, viral, steatohepatitis), cholangitis or any known elevation of liver aminotransferases with AST or ALT > 3 X ULN)*
- Chronic kidney disease (stage 3 or beyond) at screening: eGFR < 60 ml/min/1.73m2*
- HIV infection, if untreated, detectable viral load or on protease inhibitor therapy
- Any clinical condition which the investigator considers would make the participant unsuitable for the trial
- Concomitant medications known to interact with favipiravir, and with nitazoxanide and matched placebo, and carry risk of toxicity for the participant (See Appendix 4)
- Current severe illness requiring hospitalisation
- Pregnancy and/ or breastfeeding
- Eligible female participants of childbearing potential and male participants with a partner of childbearing potential not willing to use highly effective contraceptive measures during the trial and within the time point specified following last trial treatment dose.
Participants enrolled in any other interventional drug or vaccine trial (co-enrolment in observational studies is acceptable).
- Considering the importance of early treatment of COVID-19 to impact viral load, the absence of chronic liver/ kidney disease will be confirmed verbally by the participant during pre- screening and Screening/Baseline visit. Safety blood samples will be collected at Screening/Baseline visit (Day 1) and test results will be examined as soon as they become available within 24 hours.
Sites / Locations
- Hospital de Infectología "Daniel Méndez Hernández" del Centro Médico Nacional La Raza
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm 1: Favipiravir + Nitazoxanide
Arm 2: Favipiravir + Nitazoxanide placebo
Arm Description
Oral Favipiravir 1800 mg twice daily on Day 1, followed by 400 mg four (4) times daily from Day 2 to Day 7 PLUS Nitazoxanide at 1000 mg twice daily on Day 1 followed by 500 mg four (4) times daily from Day 2 to Day 7
Oral favipiravir, 1800 mg twice daily on Day 1, followed by 400 mg four (4) times daily from Day 2 to Day 7 PLUS Nitazoxanide matched placebo at 1000 mg twice daily on Day 1 followed by 500 mg four (4) times daily from Day 2 to Day 7.
Outcomes
Primary Outcome Measures
Upper respiratory tract viral load at Day 5.
Quantitative polymerase chain reaction (PCR) performed on saliva samples at Day 5 of therapy
Secondary Outcome Measures
Percentage of participants with undetectable upper respiratory tract viral load after 5 days of therapy
Method of measurement: quantitative polymerase chain reaction (PCR) performed on saliva samples.
Proportion of participants with undetectable stool viral load after 7 days of therapy and 14 days post-randomisation.
Method of measurement: PCR performed on stool samples
Rate of decrease in upper respiratory tract viral load during 7 days of therapy.
Method of measurement: PCR performed on daily saliva samples
Duration of fever following commencement of medication
Methods of measurement: daily body temperature records between Day 1 and Day 7 post-randomisation
Proportion of participants with hepatotoxicity after 7day of therapy and 14 days post-randomisation.
Method of measurement: standard diagnostic laboratory assays for liver transaminases, alkaline phosphatase and bilirubin.
Proportion of participants with other medication-related toxicity after 7 days of therapy and 14 days post-randomisation.
Methods of measurement: determination of medication-related adverse events by investigators.
Proportion of participants admitted to hospital with COVID-19 related illness.
Methods of measurement: participant self-report, review of hospital records and discharge summaries
Proportion of participants admitted to ICU with COVID-19 related illness.
Methods of measurement: participant self-report, review of hospital records and discharge summaries.
Proportion of participants who have died with COVID-19 related illness
Methods of measurement: next of kin report, review of hospital records and discharge summaries.
Pharmacokinetic analysis of favipiravir and tizoxanide: Clearance (CL)
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the following primary PK parameter: Clearance (CL).
Pharmacokinetic analysis of favipiravir and tizoxanide: Volume of distribution (V)
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the following primary PK parameter: Volume of distribution (V),
Pharmacokinetic analysis of favipiravir and tizoxanide: Absorption rate constant (Ka)
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the following primary PK parameter: Absorption rate constant (Ka).
Pharmacokinetic analysis of favipiravir and tizoxanide: Maximum concentration (Cmax)
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the previous described primary PK parameters from which the following secondary parameter will be derived: Maximum concentration (Cmax),
Pharmacokinetic analysis of favipiravir and tizoxanide: Time to maximum concentration (Tmax)
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the previous described primary PK parameters from which the following secondary parameter will be derived: Time to maximum concentration (Tmax),
Pharmacokinetic analysis of favipiravir and tizoxanide: Elimination rate constant (Ke)
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the previous described primary PK parameters from which the following secondary parameter will be derived: Elimination rate constant (Ke),
Pharmacokinetic analysis of favipiravir and tizoxanide: Area Under the Curve extrapolated to infinity (AUC 80-inf).
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the previous described primary PK parameters from which the following secondary parameter will be derived:
Area Under the Curve extrapolated to infinity (AUC 80-inf)),
Pharmacodynamic analysis of favipiravir and tizoxanide: Rate of viral load decline (delta)
A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic and viral load (pharmacodynamic) data.
The model will estimate the following pharmacodynamic parameter: Rate of viral decline (delta) Maximum increase in viral load under drug treatment (Emax), Concentration to achieve half the maximum possible effects (EC50)
Pharmacodynamic analysis of favipiravir and tizoxanide: Maximum increase in viral load under drug treatment (Emax).
A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic and viral load (pharmacodynamic) data.
The model will estimate the following pharmacodynamic parameter: Maximum increase in viral load under drug treatment (Emax).
Pharmacodynamic analysis of favipiravir and tizoxanide: Concentration to achieve half the maximum possible effects (EC50)
A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic and viral load (pharmacodynamic) data.
The model will estimate the following pharmacodynamic parameter: Concentration to achieve half the maximum possible effects (EC50)
Exploratory: proportion of participants with deleterious or resistance-conferring mutations in SARS-CoV-2.
Method of measurement: deep sequencing of virus and bioinformatic analysis.
Full Information
NCT ID
NCT04918927
First Posted
June 4, 2021
Last Updated
March 22, 2023
Sponsor
Coordinación de Investigación en Salud, Mexico
Collaborators
University College, London, Centro de Investigacion y Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV), Universidad Autonoma de Guadalajara, Siegfried Rhein S.A. de C.V., Strides Pharma Science Limited, Hakken Enterprise
1. Study Identification
Unique Protocol Identification Number
NCT04918927
Brief Title
Favipiravir +/- Nitazoxanide: Early Antivirals Combination Therapy in COVID-19
Acronym
FANTAZE
Official Title
Favipiravir and/or Nitazoxanide: a Randomized, Double-blind, Placebo-controlled Trial of Early Antiviral Therapy in COVID-19 (FANTAZE)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
October 12, 2021 (Actual)
Primary Completion Date
March 21, 2023 (Actual)
Study Completion Date
March 21, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Coordinación de Investigación en Salud, Mexico
Collaborators
University College, London, Centro de Investigacion y Estudios Avanzados del Instituto Politecnico Nacional (CINVESTAV), Universidad Autonoma de Guadalajara, Siegfried Rhein S.A. de C.V., Strides Pharma Science Limited, Hakken Enterprise
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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 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 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.
The plan is to conduct a proof-of-principle placebo-controlled clinical trial of favipiravir plus or minus nitazoxanide in health workers, their household members and IMSS beneficiaries. Participants with or without symptomatic COVID-19 or 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.
Detailed Description
FANTAZE is a Phase IIA randomised, double-blind, placebo-controlled, interventional trial.Participants will be adults who have developed the early symptoms of COVID-19 within the first 5 days, or tested positive for SARS-CoV-2 within the first 7 days of symptom onset, or not presenting symptoms but tested positive within the last 48 hours (date/time of test must be within 48 hours of enrolment).
Eligible participants will be randomised 1:1 to receive one of the following combinations:
Favipiravir + Nitazoxanide (both active); Favipiravir active + Nitazoxanide placebo;
All participants will be enrolled and followed up for 28 days. A saliva sample for virological analysis and safety blood samples will be collected at baseline, as well as a diagnostic nose and throat swab, if the participant hasn't been tested for COVID-19 yet. Following randomisation, participants will take trial medication for 7 days and during this period will take a daily saliva sample and complete a symptoms diary including four daily temperature measurements.
Participants will have two follow-up visits at Day 7 and Day 14 where they will be assessed and undergo blood tests for toxicity and pharmacokinetic assessment (on Day 7 only) and provide stool samples. Participants will have a telephone follow up three (3) weeks after their last day of treatment (Day 7) and further information will be collected through a questionnaire.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Phase IIA randomised, double-blind, placebo-controlled, interventional trial.
Masking
ParticipantCare ProviderInvestigator
Masking Description
Double-blind
Allocation
Randomized
Enrollment
120 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1: Favipiravir + Nitazoxanide
Arm Type
Experimental
Arm Description
Oral Favipiravir 1800 mg twice daily on Day 1, followed by 400 mg four (4) times daily from Day 2 to Day 7 PLUS Nitazoxanide at 1000 mg twice daily on Day 1 followed by 500 mg four (4) times daily from Day 2 to Day 7
Arm Title
Arm 2: Favipiravir + Nitazoxanide placebo
Arm Type
Experimental
Arm Description
Oral favipiravir, 1800 mg twice daily on Day 1, followed by 400 mg four (4) times daily from Day 2 to Day 7 PLUS Nitazoxanide matched placebo at 1000 mg twice daily on Day 1 followed by 500 mg four (4) times daily from Day 2 to Day 7.
Intervention Type
Drug
Intervention Name(s)
Favipiravir
Intervention Description
Oral Favipiravir 1800 mg twice daily on Day 1, followed by 400 mg four (4) times daily from Day 2 to Day 7
Intervention Type
Drug
Intervention Name(s)
Nitazoxanide
Other Intervention Name(s)
Daxon
Intervention Description
Nitazoxanide at 1000 mg twice daily on Day 1 followed by 500 mg four (4) times daily from Day 2 to Day 7
Intervention Type
Other
Intervention Name(s)
Nitazoxanide Placebo
Other Intervention Name(s)
Daxon Placebo
Intervention Description
Nitazoxanide matched placebo at 1000 mg twice daily on Day 1 followed by 500 mg four (4) times daily from Day 2 to Day 7.
Primary Outcome Measure Information:
Title
Upper respiratory tract viral load at Day 5.
Description
Quantitative polymerase chain reaction (PCR) performed on saliva samples at Day 5 of therapy
Time Frame
Day 5 from randomisation
Secondary Outcome Measure Information:
Title
Percentage of participants with undetectable upper respiratory tract viral load after 5 days of therapy
Description
Method of measurement: quantitative polymerase chain reaction (PCR) performed on saliva samples.
Time Frame
Day 5 from randomisation
Title
Proportion of participants with undetectable stool viral load after 7 days of therapy and 14 days post-randomisation.
Description
Method of measurement: PCR performed on stool samples
Time Frame
Day 7 and Day 14 from randomization
Title
Rate of decrease in upper respiratory tract viral load during 7 days of therapy.
Description
Method of measurement: PCR performed on daily saliva samples
Time Frame
From day of randomisation to day 7
Title
Duration of fever following commencement of medication
Description
Methods of measurement: daily body temperature records between Day 1 and Day 7 post-randomisation
Time Frame
From day of randomisation to day 7
Title
Proportion of participants with hepatotoxicity after 7day of therapy and 14 days post-randomisation.
Description
Method of measurement: standard diagnostic laboratory assays for liver transaminases, alkaline phosphatase and bilirubin.
Time Frame
Day 7 and day 14 from randomisation.
Title
Proportion of participants with other medication-related toxicity after 7 days of therapy and 14 days post-randomisation.
Description
Methods of measurement: determination of medication-related adverse events by investigators.
Time Frame
Day 7 and Day 14 from randomisation.
Title
Proportion of participants admitted to hospital with COVID-19 related illness.
Description
Methods of measurement: participant self-report, review of hospital records and discharge summaries
Time Frame
28 days from randomisation.
Title
Proportion of participants admitted to ICU with COVID-19 related illness.
Description
Methods of measurement: participant self-report, review of hospital records and discharge summaries.
Time Frame
28 days from randomisation.
Title
Proportion of participants who have died with COVID-19 related illness
Description
Methods of measurement: next of kin report, review of hospital records and discharge summaries.
Time Frame
28 days from randomisation.
Title
Pharmacokinetic analysis of favipiravir and tizoxanide: Clearance (CL)
Description
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the following primary PK parameter: Clearance (CL).
Time Frame
Day 7 from randomization
Title
Pharmacokinetic analysis of favipiravir and tizoxanide: Volume of distribution (V)
Description
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the following primary PK parameter: Volume of distribution (V),
Time Frame
Day 7 from randomization
Title
Pharmacokinetic analysis of favipiravir and tizoxanide: Absorption rate constant (Ka)
Description
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the following primary PK parameter: Absorption rate constant (Ka).
Time Frame
Day 7 from randomization
Title
Pharmacokinetic analysis of favipiravir and tizoxanide: Maximum concentration (Cmax)
Description
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the previous described primary PK parameters from which the following secondary parameter will be derived: Maximum concentration (Cmax),
Time Frame
Day 7 from randomization
Title
Pharmacokinetic analysis of favipiravir and tizoxanide: Time to maximum concentration (Tmax)
Description
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the previous described primary PK parameters from which the following secondary parameter will be derived: Time to maximum concentration (Tmax),
Time Frame
Day 7 from randomization
Title
Pharmacokinetic analysis of favipiravir and tizoxanide: Elimination rate constant (Ke)
Description
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the previous described primary PK parameters from which the following secondary parameter will be derived: Elimination rate constant (Ke),
Time Frame
Day 7 from randomization
Title
Pharmacokinetic analysis of favipiravir and tizoxanide: Area Under the Curve extrapolated to infinity (AUC 80-inf).
Description
Methods of measurement: assay of favipiravir and tizoxanide levels in plasma at Day 7 of therapy. All participants from each arm will provide a pre-dose sample and two post-dose (30 to 60 min) samples on Day 7 of therapy. A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic data.
The model will estimate the previous described primary PK parameters from which the following secondary parameter will be derived:
Area Under the Curve extrapolated to infinity (AUC 80-inf)),
Time Frame
Day 7 from randomization
Title
Pharmacodynamic analysis of favipiravir and tizoxanide: Rate of viral load decline (delta)
Description
A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic and viral load (pharmacodynamic) data.
The model will estimate the following pharmacodynamic parameter: Rate of viral decline (delta) Maximum increase in viral load under drug treatment (Emax), Concentration to achieve half the maximum possible effects (EC50)
Time Frame
Day 7 from randomization
Title
Pharmacodynamic analysis of favipiravir and tizoxanide: Maximum increase in viral load under drug treatment (Emax).
Description
A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic and viral load (pharmacodynamic) data.
The model will estimate the following pharmacodynamic parameter: Maximum increase in viral load under drug treatment (Emax).
Time Frame
Day 7 from randomization
Title
Pharmacodynamic analysis of favipiravir and tizoxanide: Concentration to achieve half the maximum possible effects (EC50)
Description
A nonlinear mixed effects model will be fitted jointly to favipiravir and tizoxanide pharmacokinetic and viral load (pharmacodynamic) data.
The model will estimate the following pharmacodynamic parameter: Concentration to achieve half the maximum possible effects (EC50)
Time Frame
Day 7 from randomization
Title
Exploratory: proportion of participants with deleterious or resistance-conferring mutations in SARS-CoV-2.
Description
Method of measurement: deep sequencing of virus and bioinformatic analysis.
Time Frame
Day 7 from randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Health workers, their household members and, IMSS beneficiaries with the following:
Symptoms compatible with COVID-19 disease (Fever >37.8oC on at least one occasion AND either cough and/ or anosmia) within the first 5 days of symptom onset (date/time of enrolment must be within the first 5 days of symptom onset)
OR ANY symptoms compatible with COVID-19 disease (may include, but are not limited to fever, cough, shortness of breath, malaise, myalgia, headache, coryza) and tested positive for SARS-CoV-2 within the first 7 days of symptom onset (date/time of enrolment must be within the first 7 days of symptom onset)
OR no symptoms but tested positive for SARS-CoV-2 within the last 48 hours (date/time of test must be within 48 hours of enrolment)
Male or female aged 18 years to 70 years old inclusive at screening
Willing and able to take daily saliva samples
Able to provide full informed consent and willing to comply with trial-related procedures
Exclusion Criteria:
Known hypersensitivity to any of the active ingredients or excipients in favipiravir, and in nitazoxanide and matched placebo
Chronic liver disease at screening (known cirrhosis of any aetiology, chronic hepatitis (e.g. autoimmune, viral, steatohepatitis), cholangitis or any known elevation of liver aminotransferases with AST or ALT > 3 X ULN)*
Chronic kidney disease (stage 3 or beyond) at screening: eGFR < 60 ml/min/1.73m2*
HIV infection, if untreated, detectable viral load or on protease inhibitor therapy
Any clinical condition which the investigator considers would make the participant unsuitable for the trial
Concomitant medications known to interact with favipiravir, and with nitazoxanide and matched placebo, and carry risk of toxicity for the participant (See Appendix 4)
Current severe illness requiring hospitalisation
Pregnancy and/ or breastfeeding
Eligible female participants of childbearing potential and male participants with a partner of childbearing potential not willing to use highly effective contraceptive measures during the trial and within the time point specified following last trial treatment dose.
Participants enrolled in any other interventional drug or vaccine trial (co-enrolment in observational studies is acceptable).
Considering the importance of early treatment of COVID-19 to impact viral load, the absence of chronic liver/ kidney disease will be confirmed verbally by the participant during pre- screening and Screening/Baseline visit. Safety blood samples will be collected at Screening/Baseline visit (Day 1) and test results will be examined as soon as they become available within 24 hours.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jorge Escobedo, Dr.
Organizational Affiliation
Instituto Mexicano del Seguro Social
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital de Infectología "Daniel Méndez Hernández" del Centro Médico Nacional La Raza
City
Ciudad de Mexico
State/Province
Azcapotzalco
ZIP/Postal Code
02290
Country
Mexico
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
No plan to share IPD has been made at this time
Citations:
PubMed Identifier
35869526
Citation
Smith T, Hoyo-Vadillo C, Adom AA, Favari-Perozzi L, Gastine S, Dehbi HM, Villegas-Lara B, Mateos E, Gonzalez YSP, Navarro-Gualito MD, Cruz-Carbajal AS, Cortes-Vazquez MA, Bekker-Mendez C, Aguirre-Alvarado C, Aguirre-Gil G, Delgado-Pastelin L, Owen A, Lowe D, Standing J, Escobedo J. Favipiravir and/or nitazoxanide: a randomized, double-blind, 2x2 design, placebo-controlled trial of early therapy in COVID-19 in health workers, their household members, and patients treated at IMSS (FANTAZE). Trials. 2022 Jul 22;23(1):583. doi: 10.1186/s13063-022-06533-0. Erratum In: Trials. 2023 May 22;24(1):347.
Results Reference
derived
Learn more about this trial
Favipiravir +/- Nitazoxanide: Early Antivirals Combination Therapy in COVID-19
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