Efficacy and Safety of Favipiravir in Management of COVID-19 (FAV-001)

• ClinicalTrials.gov Identifier: NCT04349241
• Recruitment Status: Completed
• First Posted: April 16, 2020
• Last Update Posted: June 25, 2020
• Sponsor: Ain Shams University
• Information provided by (Responsible Party): Hany Dabbous, Ain Shams University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Coronavirus Disease (COVID-19)	Drug: favipiravir; Drug: Standard of care therapy	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• 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
• Official Title: Efficacy and Safety of Favipiravir in Management of COVID-19
• Actual Study Start Date: April 18, 2020
• Actual Primary Completion Date: June 1, 2020
• Actual Study Completion Date: June 20, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: favipiravir; 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	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
Active Comparator: 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.	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

Outcome Measures

Primary Outcome Measures :

1. Viral clearance [ Time Frame: 14 days ]
   Two successive negative COVID-19 PCR analysis tests 48-72 hours apart
2. Clinical improvement [ Time Frame: 14 days ]
   Normal body temperature for 48 hours

Secondary Outcome Measures :

1. Radiological Improvement [ Time Frame: 14 days ]
   Improvement of radiological abnormalities at day 14

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Egypt

Faculty of Medicine Ain Shams University Research Institute- Clinical Research Center

Cairo, Non-US, Egypt, 11566

Sponsors and Collaborators

Ain Shams University

Investigators

• Principal Investigator: Hany Dabbous; Ain Shams University

More Information

• Responsible Party: Hany Dabbous, Assistant professor of Faculty of Medicine, Ain Shams University
• ClinicalTrials.gov Identifier: NCT04349241
• Other Study ID Numbers: FMASU P14 / 2020
• First Posted: April 16, 2020
• Last Update Posted: June 25, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Favipiravir; Antiviral Agents; Anti-Infective Agents