Efficacy and Safety of Favipiravir and Ribavirin Formulation for Treatment of COVID-19

COVID-19 Clinical Trial

— COVID-19  

Official title:

An Open-Label, Multicenter, Parallel-Group, Randomized, Phase II/III Study to Evaluate the Efficacy and Safety of Favipiravir and Ribavirin Formulation for Treatment of COVID-19

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04828564
• Other study ID #: MON775.159.4
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: April 2021
• Est. completion date: December 31, 2021

Study information

• Verified date: April 2021
• Source: The Scientific and Technological Research Council of Turkey
• Contact: Alpay Azap, MD, Prof
• Phone: +90 312 508 2681
• Email: azap[@]medicine.ankara.edu.tr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a national, multicenter, open-label, randomized, phase II/III trial that evaluates the efficacy and safety of favipiravir and ribavirin in the treatment of patients with confirmed COVID-19 observed within 72 hours. Approximately 100 patients will be randomized in 1:1 ratio and divided into two groups.

Description:

The clinical picture of COVID-19 disease is in a broad spectrum, which includes asymptomatic infection, a mild upper respiratory tract infection, respiratory failure, and even severe viral pneumonia with death. The alarming levels of spread and severity of COVID-19 caused a global emergency and this outbreak has been characterized as a pandemic by the World Health Organization (WHO).

Coronavirus entry into host cells is an important determinant of viral infectivity and pathogenesis. SARS-CoV S1 contains a receptor-binding domain (RBD) that specifically recognizes angiotensin-converting enzyme 2 (ACE2) as its receptor. SARS-CoV spike needs to be proteolytically activated at the S1/S2 boundary, such that S1 dissociates and S2 undergoes a dramatic structural change. These SARS-CoV entry-activating proteases include cell surface protease TMPRSS2 and lysosomal proteases cathepsins. These features of SARS-CoV entry contribute to its rapid spread and severe symptoms and high fatality rates of infected patients.

Ribavirin is a guanosine analog that interferes with the replication of RNA and DNA viruses. Ribavirin was used during the Severe Acute Respiratory Syndrome (SARS) outbreak in combination with corticosteroids, which have an anti-inflammatory effect. Favipiravir is a substrate for viral RNA-dependent RNA polymerase (RdRp) and showed anti-influenza virus activity. Favipiravir is effective against other RNA viruses, poliovirus, rhinovirus, and respiratory syncytial virus and evaluated and developed as a broad spectrum anti-RNA virus drug, including lethal RNA virus infections.

According to national guidelines, Favipiravir treatment is applied to COVID-19 infection in Turkey. The main purpose of this study is to obtain efficacy and safety data for ribavirin and favipiravir in the Turkish patient cohort diagnosed with COVID-19.

This study designed as an open-label, multicenter, parallel-group, randomized, phase II/III clinical drug trial.

This study will be conducted in 4 sites.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 31, 2021
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Female or male patients aged 18 years and older infected with the SARS-CoV-2 virus.

• Patients that have COVID-19 symptoms within 72 hours and have a positive PCR test result.

• Patients in a stable clinical condition and referred as outpatient for COVID-19 infection.

• Patients who sign the informed consent before the any study procedures.

Exclusion Criteria:

• Patients who have required hospitalization.

• Patients who have required intensive care.

• Patients who do not sign the informed consent.

• Any condition that in the investigator's judgement might interfere with study procedures or the ability of the patient to adhere to and complete the study.

• Patients who have been participating in any other clinical trial.

• Severe liver failure (Child Pugh score = C, transaminase>5 times the upper limit of normal (ULN).

• Severe renal failure (GFR =30 mL/min/1.73 m2) or continuous dialysis (hemodialysis, peritoneal dialysis) or continuous renal replacement therapy.

• Severe cardiac disease.

• History of hypersensitivity to either ribavirin/favipiravir.

• Pregnant or breast-feeding.

• Patients who cannot use appropriate contraceptive method during and after the study.

• Patients who are treated with any other treatment agent for COVID-19 in the last 90 days.

• Patients who had COVID-19 vaccination.

• Patients who had ribavirin/favipiravir for any reason in the past 72 hours.

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV2

Intervention

Drug:
• Ribavirin Capsules
Ribavirin 200 mg capsules
• Favipiravir
Favipiravir 200 mg tablets

Locations

Country	Name	City	State
Turkey	Ankara City Hospital	Ankara
Turkey	Ankara University, School of Medicine	Ankara	Cebeci
Turkey	Koc University Hospital	Istanbul
Turkey	Umraniye Training and Research Hospital	Istanbul

Sponsors (5)

Lead Sponsor	Collaborator
The Scientific and Technological Research Council of Turkey	Ankara City Hospital Bilkent, Istanbul Umraniye Training and Research Hospital, Koç University, Monitor CRO

Country where clinical trial is conducted

Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hospitalized patient rates	The number of hospitalized patients	15 days
Secondary	Mortality rate	All-cause mortality rate	15 days
Secondary	Time from randomization to relief of symptoms	The duration (days) from start of treatment to relief of clinical symptoms	15 days
Secondary	Viral clearance	The day of viral clearance evaluated by real-time polymerase chain reaction (RT-PCR)	15 days
Secondary	Changes in angiotensin-converting enzyme 2 (ACE2) receptor levels	Detection of RNA and/or protein levels of ACE2 gene in plasma samples via quantitative RT-PCR and/or flow cytometry	15 days
Secondary	Changes in transmembrane protease serine II (TMPRSS2) activity	Assessment of proteolytic activity of TMPRSS2	15 days
Secondary	Emergency room visit rates of patients	The number of emergency room visits of patients (not hospitalized)	15 days
Secondary	Time to emergency room visit	The time (days) until the emergency room visit	15 days
Secondary	Time to hospitalization	The time (days) until the hospitalization	15 days
Secondary	Inpatient length of stay	Length of stay in the hospital (days)	15 days
Secondary	Time to ICU admission	The time (days) until admission to intensive care unit	15 days
Secondary	Time to intubation	The time (days) until intubation	15 days
Secondary	Family members rates with PCR positive test results	The number of family members with PCR positive	15 days
Secondary	Changes in vital signs from baseline	Clinical evaluation of systolic and diastolic blood pressure, pulse, respiratory rate, fever, oxygen saturation changes from baseline until the end of study	15 days
Secondary	Number/characteristics of AEs and SAEs	Number/characteristics of Adverse Event (AE) and Serious Adverse Event (SAE) related to study drug or hematological and biochemical parameters from baseline until the end of study	28 days