Efficacy and Safety of Hydroxychloroquine and Favipiravir in the Treatment of Mild to Moderate COVID-19

NCT ID: NCT04411433

Last Updated: 2021-02-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 1008 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-08
• Study Completion Date: 2021-06-01

Brief Summary

This is an open-label, multicenter, parallel-group, randomized, phase III trial that evaluates the efficacy and safety of hydroxychloroquine and favipiravir in the treatment of patients with possible or confirmed COVID-19 observed within the last 5 days. 1000 patients will be randomized in 2:1:2:2:2:1 ratio and divided into six groups.

Detailed Description

The clinical picture of 2019-nCoV 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. Although the mortality rate is not yet clear, the reported case-fatality risk was 11-14% during the initial studies which included patients with severe disease. The overall case fatality rate was reported as approximately 2%. In addition, most cases have resulted in a pneumonia requiring supplemental oxygen therapy and ventilator support. 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).

The investigational product Favipiravir is an antiviral drug against RNA viruses and has been stated as effective for the treatment of COVID-19, first emerged from China, in various clinical studies. In February 2020, Favipiravir was used for the clinical treatment of COVID-19, has been shown to be more effective than the lopinavir / ritonavir combination in 80 people. In recent researches, the drug favipiravir is suggested that it may induce recovery in a short time in patients with COVID-19-mild type and decrease the treatment duration from 11 days to 4 days.

The investigational product hydroxychloroquine sulfate is a 4- aminoquinoline derivative and widely used for the treatment of many rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus in addition to its antimalarial effects. In vitro studies reported that hydroxychloroquine sulfate may be effective against many viruses, including SARS-CoV-2 in many in vitro experiments. Additionally, preliminary results of limited number of studies have been revealed that hydroxychloroquine sulfate reduces virus load and induces improvement in patients with COVID-19. This agent has been also suggested to be used in COVID-19 prophylaxis.

Until now, there is no official report on whether hydroxychloroquine combined with favipiravir show clinical activity against the new coronavirus, COVID-19, in Turkey. The main purpose of this study is to evaluate the efficacy and safety of hydroxychloroquine and favipiravir in the treatment of Turkey population with COVID-19.

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

A total of 1000 subjects aged between 18 to 70 years with symptoms and complaints consistent with possible or confirmed COVID-19 observed within the last 5 days and meet all eligibility criteria will participate in the study.

This study will be conducted in 14 sites.

Conditions

Sars-CoV2; COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Favipiravir (3200 mg + 1200 mg)

Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total).

The treatment duration may be extended up to 14 days with the evaluation of principle investigator.

Group Type: EXPERIMENTAL

Favipiravir (3200 mg + 1200 mg)

Intervention Type: DRUG

Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total).

The treatment duration may be extended up to 14 days with the evaluation of principle investigator.

Favipiravir (3600 mg + 1600 mg)

Dosage and method of administration: in a regimen of 2x1800 mg (oral) loading dose on day-1 followed by 1600 mg maintenance dose (2x800 mg, 2 times daily) on day-2 to day-5 (5 days in total).

The treatment duration may be extended up to 14 days with the evaluation of principle investigator.

Group Type: EXPERIMENTAL

Favipiravir (3600 mg + 1600 mg)

Intervention Type: DRUG

Drug: Favipiravir (3600 mg + 1600 mg) Dosage and method of administration: in a regimen of 2x1800 mg (oral) loading dose on day-1 followed by 1600 mg maintenance dose (2x800 mg, 2 times daily) on day-2 to day-5 (5 days in total).

The treatment duration may be extended up to 14 days with the evaluation of principle investigator.

Favipiravir combined with Hydroxychloroquine

Hydroxychloroquine Dosage and method of administration: in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).

Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.

Group Type: EXPERIMENTAL

Favipiravir (3200 mg + 1200 mg) combined with Hydroxychloroquine

Intervention Type: DRUG

Hydroxychloroquine Dosage and method of administration: in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).

Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.

Favipiravir combined with Azithromycin

Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).

Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.

Group Type: EXPERIMENTAL

Favipiravir (3200 mg + 1200 mg) combined with Azithromycin

Intervention Type: DRUG

Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).

Favipiravir Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.

Hydroxychloroquine

Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (200 mg oral 2 times daily) on day-2 to day-5 (5 days in total).

Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (200 mg oral 2 times daily) throughout 5 days (5 days in total).

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine

Intervention Type: DRUG

Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (200 mg oral 2 times daily) on day-2 to day-5 (5 days in total).

Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (200 mg oral 2 times daily) throughout 5 days (5 days in total).

Hydroxychloroquine combined with Azithromycin

Hydroxychloroquine Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).

Hydroxychloroquine Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (2x200 mg oral, 2 times daily) throughout 5 days (5 days in total).

Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine combined with Azithromycin

Intervention Type: DRUG

Drug: Hydroxychloroquine combined with Azithromycin Hydroxychloroquine Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).

Hydroxychloroquine Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (2x200 mg oral, 2 times daily) throughout 5 days (5 days in total).

Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).

Interventions

Favipiravir (3200 mg + 1200 mg)

Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total).

The treatment duration may be extended up to 14 days with the evaluation of principle investigator.

Intervention Type: DRUG

Favipiravir (3600 mg + 1600 mg)

Drug: Favipiravir (3600 mg + 1600 mg) Dosage and method of administration: in a regimen of 2x1800 mg (oral) loading dose on day-1 followed by 1600 mg maintenance dose (2x800 mg, 2 times daily) on day-2 to day-5 (5 days in total).

The treatment duration may be extended up to 14 days with the evaluation of principle investigator.

Intervention Type: DRUG

Favipiravir (3200 mg + 1200 mg) combined with Hydroxychloroquine

Hydroxychloroquine Dosage and method of administration: in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).

Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.

Intervention Type: DRUG

Favipiravir (3200 mg + 1200 mg) combined with Azithromycin

Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).

Favipiravir Favipiravir Dosage and method of administration: in a regimen of 2x1600 mg (oral) loading dose on day-1 followed by 1200 mg maintenance dose (2x600 mg, 2 times daily) on day-2 to day-5 (5 days in total). The treatment duration may be extended up to 14 days with the evaluation of principle investigator.

Intervention Type: DRUG

Hydroxychloroquine

Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (200 mg oral 2 times daily) on day-2 to day-5 (5 days in total).

Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (200 mg oral 2 times daily) throughout 5 days (5 days in total).

Intervention Type: DRUG

Hydroxychloroquine combined with Azithromycin

Drug: Hydroxychloroquine combined with Azithromycin Hydroxychloroquine Dosage and method of administration for patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms): in a regimen of 2x400 mg (oral) loading dose on day-1 followed by 400 mg maintenance dose (2x200 mg oral, 2 times daily) on day-2 to day-5 (5 days in total).

Hydroxychloroquine Dosage and method of administration for patients with uncomplicated possible or confirmed COVID-19: in a regimen of 400 mg (2x200 mg oral, 2 times daily) throughout 5 days (5 days in total).

Azithromycin Dosage and method of administration: in a regimen of 1x500 mg (oral) loading dose on day-1 followed by 250 mg maintenance dose (oral daily) on day-2 to day-5 (5 days in total).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects aged between 18 to 70 years,
• Patients with symptoms and complaints consistent with possible or confirmed COVID- 19 observed within the last 5 days,
• Patients with uncomplicated possible or confirmed COVID-19:

1. Symptoms such as fever, muscle aches, joint pain, cough, sore throat, nasal congestion, however no respiratory distress, no tachypnea or no SpO2 < 93%,

2. Chest imaging (X-ray or CT chest) documented as normal

• Patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms):

1. Symptoms such as fever, muscle aches, joint pain, cough, sore throat, nasal congestion, as well as respiratory rate <30/min and SpO2 above 93% on room air,

2. Chest imaging (X-ray or CT chest)-documented mild pneumonia symptoms

• Patients who were decided to isolate and treat because of COVID-19 in the hospital,
• Patients who have not been involved in any other interventional studies.

Exclusion Criteria

• Patients considered as inappropriate for this study for any reason like noncompliance by the researcher,
• Patients with persisting refractory nausea, vomiting, chronic diarrhoea or chronic gastrointestinal disorders, inability to swallow the study drug which may affect adequate absorption,
• Patients with chronic liver disease: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevated over 5 times the upper limit of normal (ULN),
• Patients with gout or hyperuricemia (above the ULN),
• Patients with severe pneumonia symptoms,
• Patients with known allergy to Favipiravir or for substances used in the study,
• Patients did not receive specific antiviral drugs such as lopinavir/ritonavir, ribavirin, arbidol, chloroquine phosphate, hydroxychloroquine, and monoclonal antibodies within one week before admission.
• Patients with known chronic renal impairment/failure [creatinine clearance (CcCl) <30 mL/min],
• Pregnant and lactating women
• Patients undergoing cardiac ablation therapy
• Patients using antiarrhythmic drugs
• Patients actively receiving chemotherapy
• Acute immunosuppressed patients
• Patients undergoing psychosis therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hacettepe University, Faculty of Medicine

UNKNOWN

Sponsor Role: collaborator

Prof. Dr. Cemil Tascıoglu Education and Research Hospital Organization

OTHER

Sponsor Role: collaborator

Umraniye Education and Research Hospital

OTHER_GOV

Sponsor Role: collaborator

SB Istanbul Education and Research Hospital

OTHER

Sponsor Role: collaborator

Sultan Abdulhamid Han Training and Research Hospital, Istanbul, Turkey

OTHER

Sponsor Role: collaborator

Tepecik Training and Research Hospital

OTHER

Sponsor Role: collaborator

Istanbul University - Cerrahpasa

OTHER

Sponsor Role: collaborator

Ankara University

OTHER

Sponsor Role: collaborator

Ankara City Hospital Bilkent

OTHER

Sponsor Role: collaborator

Ankara Training and Research Hospital

OTHER

Sponsor Role: collaborator

Ege University Hospital (Application and Research Center)

UNKNOWN

Sponsor Role: collaborator

Kocaeli Derince Education and Research Hospital

OTHER

Sponsor Role: collaborator

Istanbul University

OTHER

Sponsor Role: collaborator

Kayseri City Hospital

OTHER_GOV

Sponsor Role: collaborator

Ministry of Health, Turkey

OTHER_GOV

Sponsor Role: lead

Responsible Party

Prof. Ates KARA, MD

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hacettepe University, School of Medicine

Ankara, , Turkey (Türkiye)

Countries

Turkey (Türkiye)

Other Identifiers

COVID-19-FAV

Identifier Type: -

Identifier Source: org_study_id