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.
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.
Drug: favipiravir
pyrazine carboxamide derivative (6-fluoro-3-hydroxy-2-pyrazinecarboxamide), a new type of RNA-dependent RNA polymerase (RdRp) inhibitor
Other Name: pyrazine carboxamide derivative
Drug: Standard of care therapy
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 Name: National Egyptian guideline
Inclusion Criteria:
Patients aged between 18 and 80 years.
Patients with confirmed COVID-19 documented by a diagnostic laboratory test (e.g.,
nasopharyngeal swab) at the time of illness.
And Have mild to moderate symptoms according to the national protocol classification of
patients.
Exclusion Criteria:
Patients have severe or immediately life-threatening COVID-19, Severe disease is defined
as: dyspnea, respiratory frequency ≥ 30/min, blood oxygen saturation ≤ 93%, partial
pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, and/or lung
infiltrates > 50% within 24 to 48 hours Life-threatening disease is defined as: respiratory
failure, septic shock, and/or multiple organ dysfunction or failure
Pregnant or lactating females.
Participation in any investigational clinical study, other than observational, within the
past 30 days; or plans to participate in such a study at any time from the day of
enrollment until 30 days post-treatment in the current study.
Faculty of Medicine Ain Shams University Research Institute- Clinical Research Center
Cairo, Non-US, Egypt
Hany Dabbous, Principal Investigator
Ain Shams University