Clinical trial NCT04828564: Efficacy and Safety of Favipiravir and Ribavirin Formulation for Treatment of 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: SARS-CoV2
COVID-19
Lead sponsor: The Scientific and Technological Research Council of Turkey
Sponsor class: OTHER
Collaborators: name: Ankara City Hospital Bilkent
name: Istanbul Umraniye Training and Research Hospital
name: Koç University
name: Monitor CRO
First posted: 2021-04-02
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hospitalized patient rates
timeFrame: 15 days
Secondary outcomes:
measure: Mortality rate
timeFrame: 15 days
measure: Time from randomization to relief of symptoms
timeFrame: 15 days
measure: Viral clearance
timeFrame: 15 days
measure: Changes in angiotensin-converting enzyme 2 (ACE2) receptor levels
timeFrame: 15 days
measure: Changes in transmembrane protease serine II (TMPRSS2) activity
timeFrame: 15 days
measure: Emergency room visit rates of patients
timeFrame: 15 days
measure: Time to emergency room visit
timeFrame: 15 days
measure: Time to hospitalization
timeFrame: 15 days
measure: Inpatient length of stay
timeFrame: 15 days
measure: Time to ICU admission
timeFrame: 15 days
measure: Time to intubation
timeFrame: 15 days
measure: Family members rates with PCR positive test results
timeFrame: 15 days
measure: Changes in vital signs from baseline
timeFrame: 15 days
measure: Number/characteristics of AEs and SAEs
timeFrame: 28 days
Other outcomes:
Locations:
city: Ankara
country: Turkey
facility: Ankara University, School of Medicine
state: Cebeci
city: Ankara
country: Turkey
facility: Ankara City Hospital
city: Istanbul
country: Turkey
facility: Koc University Hospital
city: Istanbul
country: Turkey
facility: Umraniye Training and Research Hospital
Study officials:
References: