Efficacy and Safety of Favipiravir in Management of COVID-19
Condition: Coronavirus Disease (COVID-19)
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 3

Summary: 
      Randomized controlled interventional trial (Clinical Trial) phase 3 to assess the safety and
      efficacy of favipiravir versus the standard care therapy in the treatment of patients with
      COVID-19.
    

Detailed description: 
      Study Procedures:

      Screening phase:

        -  Obtaining an informed consent

             -  Written signed and dated informed consent will be obtained from each patient before
                being entered into the study. The investigator, or a person designated by the
                investigator, should fully inform the subject or, if the subject is unable to
                provide informed consent, the subject's legally acceptable representative, of all
                pertinent aspects of the trial. This will be obtained from each subject in
                accordance with the recommendation of the revised Declaration of Helsinki. The
                investigator will explain the nature, purpose and risks of the study. It will be
                clearly stated that the patient is free to withdraw from the study at any time for
                any reason without prejudice to future care, and with no obligation to give the
                reason for withdrawal.

             -  In case the patient is unable to provide his/her consent the legal guardian will
                give verbal approval on behaves of the patient and after he he/she will be well
                informed by the study design, procedure, risk and benefits over phone call.

             -  If it is difficult to reach the legal guardian, emergency approval will be obtained
                by Professional Legal Representative who will be the head authorities of the
                isolation hospital.

        -  Full medical history, concurrent medications, demographic data will be obtained.

        -  A thorough physical examination will be performed.

        -  Body weight, height, BMI, vital signs (blood pressure, heart rate and temperature) and
           Blood oxygen saturation) will be recorded.

        -  Chest X-ray or CT chest will be recorded.

        -  Laboratory to perform the following tests:

      Complete blood count with differential counts, COVID -19 PCR test by nasopharyngeal swab.
      C-reactive protein and serum ferritin level. Renal function tests (RFTs) (serum creatinine),
      Liver function tests (LFTs) (alanine amino transferase (ALT), aspartate amino transferase
      (AST), total and direct bilirubin), Coagulation test; prothrombin time and INR. HIV antibody,
      HCV antibody and HBV surface antigen (HBsAg). Urine pregnancy test for females.

      Treatment phase for eligible patients:

        -  Eligibility confirmed

        -  The patient will receive information regarding the treatment duration, how to take the
           study treatment and the dose of the study treatment.

        -  The patient will receive information regarding the identification and notification of
           adverse events as diarrhea that occurs in about 25 % of patients and mild elevation of
           transaminases.

        -  The patient will be advised to record the daily dosing of study medications that were
           taken in diaries. If the patient is fatigued or uneducated the clinical pharmacist or
           the treating physician will be responsible for recording.

        -  Concomitant medications will also be recorded.

        -  Eligible patients in group 1 will be given favipiravir in a regimen of 3200 mg (1600 mg
           12 hourly) loading dose on day-1 followed by 1200 mg maintenance dose (600 mg 12 hourly
           daily) on day-2 to day-10.

        -  Eligible patients in group 2 will receive oseltamivir 75 mg 12 hourly for 5-10 days and
           hydroxychloroquine 400mg 12 hourly day -1 followed by 200mg 12 hourly daily on day- 2 to
           day-5-10.

        -  Clinical assessment will be performed on days 3 and 7 and adverse events will be
           recorded.

        -  Laboratory follow up: Days 3 and 7 of treatment

             -  Liver function tests (ALT and AST).

             -  COVID -19 PCR test by nasopharyngeal swab.

             -  C-reactive protein and serum ferritin levels. End point of the study: Day 14
                assessment

        -  The patient's health status and the presence of adverse events will be assessed.

        -  Complete physical examination.

        -  Vital signs (blood pressure, heart rate and temperature) will be recorded.

        -  Follow-up CXR and /or CT scan.

        -  Liver function tests (LFTs) (alanine amino transferase (ALT), aspartate amino
           transferase (AST), total and direct bilirubin).

        -  C-reactive protein and serum ferritin level.

        -  COVID -19 PCR test by nasopharyngeal swab

        -  Post treatment period up to 30 days after end of treatment:

        -  Vital signs (blood pressure, heart rate and temperature) will be recorded.

        -  Symptoms and signs assessment will be done.
    

Intervention name(s): favipiravir; Standard of care therapy
Intervention type(s): Drug; Drug
Intervention description(s): pyrazine carboxamide derivative (6-fluoro-3-hydroxy-2-pyrazinecarboxamide), a new type of RNA-dependent RNA polymerase (RdRp) inhibitor; oseltamivir 75 mg 12 hourly for 5-10 days and hydroxychloroquine 400mg 12 hourly day -1 followed by 200mg 12 hourly daily on day- 2 to day-5-10
Other intervention name(s): pyrazine carboxamide derivative; National Egyptian guideline
Intervention MeSH terms: Favipiravir
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A block-randomization scheme will be generated by computer software. 100 patients with confirmed COVID-19 will be randomized between favipiravir and the standard of care therapy (treated according to the national protocol) in a 1:1 ratio.
Group 1: 50 patients will receive the investigational drug favipiravir. Group 2: 50 patients will receive oseltamivir and hydroxychloroquine as the national standard of care therapy.
Masking: None (Open Label)
Primary purpose: Treatment