Favipiravir Therapy in Adults With Mild COVID-19 (Avi-Mild)

• ClinicalTrials.gov Identifier: NCT04464408
• Recruitment Status: Completed
• First Posted: July 9, 2020
• Last Update Posted: November 5, 2021
• Sponsor: King Abdullah International Medical Research Center
• Collaborator: Ministry of Health, Saudi Arabia
• Information provided by (Responsible Party): King Abdullah International Medical Research Center

Study Description

Brief Summary:

Favipiravir is a selective and potent inhibitor of influenza viral RNA polymerase. It acts as a purine analogue, which selectively inhibits viral RNA-dependent RNA polymerase (RdRps). It has the characteristic of acting on RNA viruses including Ebola and Coronaviruses especially novel coronavirus (2019-nCoV). The purpose of this study is to evaluate the clinical efficacy and safety of Favipiravir in comparison to placebo in the treatment of mild COVID-19 cases. It is a Multicenter, randomized double-blinded, parallel-group trial.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Favipiravir; Drug: Placebo	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 231 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Trial of Favipiravir Therapy in Adults With Mild Coronavirus Disease COVID-19
• Actual Study Start Date: July 23, 2020
• Actual Primary Completion Date: August 4, 2021
• Actual Study Completion Date: August 4, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Favipiravir; Favipiravir: 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (Maximum days of therapy is 7 days)	Drug: Favipiravir; 1800 mg twice daily for one day, followed by 800mg (4 tablets) twice daily
Placebo Comparator: Placebo; 9 tablets by mouth twice daily for one day, followed by 4 tablets twice daily (Maximum days of therapy is 7 days).	Drug: Placebo; (9 tablets) by mouth twice daily for one day, followed by (4 tablets) twice daily (Maximum days of therapy is 7 days)

Outcome Measures

Primary Outcome Measures :

1. PCR negative [ Time Frame: 15 days ]
   Time from randomization to negativity in RT-PCR nucleic acid test for COVID-19 within 15 days of randomization

Secondary Outcome Measures :

1. Time from randomization to clinical recovery [ Time Frame: 15 days ]
   The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory symptoms, and relief of cough (or other relevant symptoms at enrollment) that is maintained for at least 72 hours.
2. Evaluate symptoms progression [ Time Frame: 28 days ]
   Evaluate symptoms severity and the disease course progression in both arms till 28 days after starting the medicine.
3. Evaluate Faviparivirs effect [ Time Frame: 15 days ]
   To evaluate Favipiravir's effect on the requirement of the use of antipyretics, analgesics, or antibiotics within 15 days after starting medicine.
4. Evaluate Favipiravir's effect [ Time Frame: 28 days ]
   To evaluate Favipiravir's effect on disease complications within 28 days after starting medicine (hospitalization, ICU admission, or Mechanical ventilation )
5. Evaluate the safety of Favipiravir [ Time Frame: 28 days ]
   Evaluate the safety of investigational drug compared to the control arm within 15 days after starting the medicine. This is assessed by allergic reactions, medication intolerance, liver toxicity, and hyperuricemia in subjects

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria

Patients must be eligible according to the following criteria for enrollment

1. Should be at least 18 years of age
2. Male or non-pregnant female (pregnancy testing is not mandatory. If the patient requests or is not sure, the study team will provide it)
3. Diagnosed with mild COVID-19* confirmed by positive PCR test for SARS-CoV-2 at the time of recruitment, a result within the last five days
4. Patients have to be enrolled within 5 days of disease onset.

Exclusion criteria

Patients meeting any of the following criteria will be excluded from trial enrolment:

1. Patients with concomitant documented bacterial pneumonia established through positive sputum cultures
2. Patients who are pregnant or breastfeeding
3. Known sensitivity/allergy to Favipiravir (If Faviparavir was used for COVID-19 in the patient previously for influenza)

4. Major comorbidities increasing the risk of study drug including

   • Hematologic malignancy
   • Advanced (stage 4-5) chronic kidney disease or dialysis therapy
   • Severe liver damage (Child-Pugh score C, AST> 5 times the upper limit)
   • HIV
   • Gout/history of Gout or hyperuricemia (two times above the ULN)

(6) Having used Favipiravir or participated in any other interventional drug clinical study within 30 days before the first dose of study drug (i.e., the patient received it for influenza previously) (7) The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues) (8) Clinical prognostic non-survival, palliative care, or in a deep coma and have no response to supportive treatment within three hours of admission.

(9) Hospitalized patients for mild, moderate, or severe COVID-19

Contacts and Locations

Locations

Saudi Arabia

Prince Mohammed Bin Abdul Aziz Hospital - Al Madinah

Al Madinah, Saudi Arabia

King Fahad Hospital - Madinah

Al Madīnah, Saudi Arabia

Primary Health Care-Safiyah

Al Madīnah, Saudi Arabia

King Abdullah Medical City - Makkah

Mecca, Saudi Arabia

King Abdulaziz Medical City - Riyadh

Riyadh, Saudi Arabia

Primary Health Care-Al Mansoura

Riyadh, Saudi Arabia

Primary Health Care-Al Urijah

Riyadh, Saudi Arabia

Sponsors and Collaborators

King Abdullah International Medical Research Center

Ministry of Health, Saudi Arabia

Investigators

• Principal Investigator: Mohammad Bosaeed; KAMC-RD, Ministry of National Guard Health Affairs (MNGHA), Saudi Arabia

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bosaeed M, Alharbi A, Hussein M, Abalkhail M, Sultana K, Musattat A, Alqahtani H, Alshamrani M, Mahmoud E, Alothman A, Alsaedy A, Aldibasi O, Alhagan K, Asiri AM, AlJohani S, Al-Jeraisy M, Alaskar A. Multicentre randomised double-blinded placebo-controlled trial of favipiravir in adults with mild COVID-19. BMJ Open. 2021 Apr 14;11(4):e047495. doi: 10.1136/bmjopen-2020-047495.

• Responsible Party: King Abdullah International Medical Research Center
• ClinicalTrials.gov Identifier: NCT04464408
• Other Study ID Numbers: RC 20/220/R
• First Posted: July 9, 2020
• Last Update Posted: November 5, 2021
• Last Verified: November 2021

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

Keywords provided by King Abdullah International Medical Research Center:

Favipiravir; COVID19; Mild illness; Saudi Arabia

Additional relevant MeSH terms:

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