Favipiravir +/- Nitazoxanide: Early Antivirals Combination Therapy in COVID-19
Condition: Covid19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Favipiravir; Nitazoxanide; Nitazoxanide Placebo
Intervention type(s): Drug; Drug; Other
Intervention description(s): Oral Favipiravir 1800 mg twice daily on Day 1, followed by 400 mg four (4) times daily from Day 2 to Day 7; Nitazoxanide at 1000 mg twice daily on Day 1 followed by 500 mg four (4) times daily from Day 2 to Day 7; 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.
Other intervention name(s): Daxon; Daxon Placebo
Intervention MeSH terms: Nitazoxanide; Favipiravir
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase IIA randomised, double-blind, placebo-controlled, interventional trial.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment