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The Efficacy and Adverse Effects of Favipiravir on COVID-19 Patients: A Systematic Review and Meta-Analysis of Published Clinical Trials and Observational Studies

37 Pages Posted: 20 Jul 2021

See all articles by Dang The Hung

Dang The Hung

University of Medicine and Pharmacy, Ho Chi Minh City - Faculty of Medicine

Suhaib Ghula

The University of Buckingham - School of Medicine

Jeza Abdul Aziz

University of Human Development - Department of Medical Laboratory Science

Abdelrahman M Makram

October 6 University (O6U) - Faculty of Medicine; Imperial College London - School of Public Health; October 6 University (O6U) - Orthopaedic Department

Gehad Mohamed Tawfik

Ain Shams University - Faculty of Medicine

Ali Ahmed-Fouad Abozaid

Ain Shams University - Faculty of Medicine

Rohan Andrew Pancharatnam

The University of Buckingham - School of Medicine

Amr Mohamed Ibrahim

South Valley University - Faculty of Medicine

Muhammad Besher Shabouk

University of Aleppo - Faculty of Medicine

Morgan Turnage

American University of the Caribbean - School of Medicine

Saloni Nakhare

The University of Buckingham - School of Medicine

Zahra Karmally

The University of Buckingham - School of Medicine

Basel Kouz

Damascus University - Faculty of Medicine

Tran Nhat Le

Hue University of Medicine and Pharmacy - Faculty of Medicine

Suleiman Alhijazeen

Mutah University - Graduate of Faculty of Medicine

Nguyen Quoc Phuong

Vietnam National University - Faculty of Biology - Biotechnology

Alaa Mohamed Ads

Tanta University - Faculty of Medicine

Ali Hussein Abdelaal

Aswan University - Faculty of Medicine

Nguyen Hai Nam

Kyoto University Graduate School of Medicine - Division of Hepato-Biliary-Pancreatic Surgery and Transplantation; Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Tatsuo Iiyama

National Center for Global Health and Medicine (NCGM) - Department of International Trials

Kyoshi Kita

Nagasaki University - School of Tropical Medicine and Global Health

Kenji Hirayama

Nagasaki University - School of Tropical Medicine and Global Health; Nagasaki University - Department of Immunogenetics

Nguyen Tien Huy

Nagasaki University - School of Tropical Medicine and Global Health; Nagasaki University - Department of Clinical Product Development

More...

Abstract

Background: The burden of COVID-19 on healthcare systems worldwide requires an efficient treatment option. Favipiravir, a nucleoside analog, is a potential COVID-19 treatment. Therefore, this study aimed to evaluate the efficacy and adverse events of favipiravir in COVID-19 patients.

Method: In our systematic review and meta-analysis, we performed searches of PubMed, Scopus, Embase, Web of Science, the Cochrane Library, Google Scholar, European PMC, Virtual Health Library, mRCT, ClinicalTrials.gov, SIGLE, the WHO COVID-19 research article database, Covid-evidence.org, and the iSearch COVID-19 Portfolio with the latest update on February 8 th , 2021. All types of studies in which favipiravir was used on COVID-19 patients were included and extracted by two independent authors. All studies underwent systematic review, data from controlled trials underwent meta-analysis. Our protocol was registered on PROSPERO as CRD42020206305.

Findings: 145 studies (15 randomized controlled trials (RCTs), one non-RCT, 21 observational studies, two case series, and 106 case reports) were included. In comparison to standard of care (SOC), favipiravir showed a higher rate of viral clearance at day 5 (RR=1·49, p=0·03), defervescence at day 3 (RR=1·91, p<0·01), chest computed tomography (CT) improvement at day 14-15 (RR=1·40, p<0·01), and hospital discharge at day 10-11 (RR=1·31, p<0·01). Regarding adverse events, the favipiravir groups had higher rates of hyperuricemia (RR=9·42, p<0·01), but lower rates of nausea (RR=0·41, p<0·01) and vomiting (RR=0·09, p=0·02).

Interpretation: Adding favipiravir to the standard of care provides better outcomes for COVID-19 patients. Pregnant and lactating women as well as a history of hyperuricemia or gouty arthritis should be noticed when using favipiravir. Using favipiravir could reduce the rate of nausea and vomiting for some patients.

Registration Details: Registered on PROSPERO as CRD42020206305.

Funding Information: Grant Asian clinical trial network construction project (Number JP20LK0201001J0001) by Japan Agency for Medical Research and Development (AMED).

Declaration of Interests: We declare no competing interests.

Suggested Citation

Hung, Dang The and Ghula, Suhaib and Aziz, Jeza Abdul and Makram, Abdelrahman and Tawfik, Gehad Mohamed and Abozaid, Ali Ahmed-Fouad and Pancharatnam, Rohan Andrew and Ibrahim, Amr Mohamed and Shabouk, Muhammad Besher and Turnage, Morgan and Nakhare, Saloni and Karmally, Zahra and Kouz, Basel and Le, Tran Nhat and Alhijazeen, Suleiman and Phuong, Nguyen Quoc and Ads, Alaa Mohamed and Abdelaal, Ali Hussein and Nam, Nguyen Hai and Nam, Nguyen Hai and Iiyama, Tatsuo and Kita, Kyoshi and Hirayama, Kenji and Huy, Nguyen Tien, The Efficacy and Adverse Effects of Favipiravir on COVID-19 Patients: A Systematic Review and Meta-Analysis of Published Clinical Trials and Observational Studies. Available at SSRN: https://ssrn.com/abstract=3889346 or http://dx.doi.org/10.2139/ssrn.3889346

Dang The Hung

University of Medicine and Pharmacy, Ho Chi Minh City - Faculty of Medicine ( email )

217 Hong Bang street, district 5, ward 11
Ho Chi Minh City, Ho Chi Minh City 700000
Vietnam

Suhaib Ghula

The University of Buckingham - School of Medicine ( email )

Hunter Street
Buckingham MK18 1EG
United Kingdom

Jeza Abdul Aziz

University of Human Development - Department of Medical Laboratory Science ( email )

Iraq

Abdelrahman Makram

October 6 University (O6U) - Faculty of Medicine ( email )

Giza
Egypt

Imperial College London - School of Public Health ( email )

London
United Kingdom

October 6 University (O6U) - Orthopaedic Department ( email )

Giza
Egypt

Gehad Mohamed Tawfik

Ain Shams University - Faculty of Medicine ( email )

Cairo
Egypt

Ali Ahmed-Fouad Abozaid

Ain Shams University - Faculty of Medicine ( email )

Cairo
Egypt

Rohan Andrew Pancharatnam

The University of Buckingham - School of Medicine ( email )

Hunter Street
Buckingham MK18 1EG
United Kingdom

Amr Mohamed Ibrahim

South Valley University - Faculty of Medicine ( email )

Egypt

Muhammad Besher Shabouk

University of Aleppo - Faculty of Medicine ( email )

Syria

Morgan Turnage

American University of the Caribbean - School of Medicine ( email )

Saloni Nakhare

The University of Buckingham - School of Medicine ( email )

Hunter Street
Buckingham MK18 1EG
United Kingdom

Zahra Karmally

The University of Buckingham - School of Medicine ( email )

Hunter Street
Buckingham MK18 1EG
United Kingdom

Basel Kouz

Damascus University - Faculty of Medicine ( email )

Damascus
Syria

Tran Nhat Le

Hue University of Medicine and Pharmacy - Faculty of Medicine

Vietnam

Suleiman Alhijazeen

Mutah University - Graduate of Faculty of Medicine

Nguyen Quoc Phuong

Vietnam National University - Faculty of Biology - Biotechnology ( email )

144 Xuan Thuy
Cau Giay
Hanoi, 84
Vietnam

Alaa Mohamed Ads

Tanta University - Faculty of Medicine ( email )

Said Street
3111 Tanta
Egypt

Ali Hussein Abdelaal

Aswan University - Faculty of Medicine

Egypt, Aswan
Aswan, 81524
Egypt

Nguyen Hai Nam

Kyoto University Graduate School of Medicine - Division of Hepato-Biliary-Pancreatic Surgery and Transplantation ( email )

Kyoto
Japan

Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. ( email )

Yoshida Honmachi
Kyoto, Kyoto 606-8501
Japan
07041136518 (Phone)
606-8501 (Fax)

Tatsuo Iiyama

National Center for Global Health and Medicine (NCGM) - Department of International Trials ( email )

Tokyo 162-8655
Japan

Kyoshi Kita

Nagasaki University - School of Tropical Medicine and Global Health ( email )

Nagasaki
Japan

Kenji Hirayama (Contact Author)

Nagasaki University - School of Tropical Medicine and Global Health ( email )

Nagasaki
Japan

Nagasaki University - Department of Immunogenetics ( email )

Nagasaki
Japan

Nguyen Tien Huy

Nagasaki University - School of Tropical Medicine and Global Health

Nagasaki
Japan

Nagasaki University - Department of Clinical Product Development ( email )

Katafuchi
Nagasaki
Nagasaki 850-8506
Japan