NCT04411433

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1,008

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started May 2020

Shorter than P25 for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 8, 2020

Completed
15 days until next milestone

First Submitted

Initial submission to the registry

May 23, 2020

Completed
10 days until next milestone

First Posted

Study publicly available on registry

June 2, 2020

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2020

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2021

Completed
Last Updated

February 1, 2021

Status Verified

January 1, 2021

Enrollment Period

8 months

First QC Date

May 23, 2020

Last Update Submit

January 29, 2021

Conditions

Sars-CoV2COVID-19

Outcome Measures

Primary Outcomes (2)

  • Time to recovery (discharge)

    The evaluation of recovery (discharge) period until 14th day after administration.

    14 days

  • Decrease in viral load

    The evaluation of decrease in viral load until 14th day after administration.

    14 days

Secondary Outcomes (13)

  • Adverse Event (AE), Serious Adverse Event (SAE) and discontinuation of treatment

    14 days

  • Frequency of occurrence of lymphopenia from baseline

    14 days

  • Frequency of occurrence of thrombocytopenia from baseline

    14 days

  • Changes in alanine aminotransferase (ALT) levels from baseline

    14 days

  • Changes in aspartate aminotransferase (AST) levels from baseline

    14 days

  • +8 more secondary outcomes

Study Arms (6)

Favipiravir (3200 mg + 1200 mg)

EXPERIMENTAL

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.

Drug: Favipiravir (3200 mg + 1200 mg)

Favipiravir (3600 mg + 1600 mg)

EXPERIMENTAL

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.

Drug: Favipiravir (3600 mg + 1600 mg)

Favipiravir combined with Hydroxychloroquine

EXPERIMENTAL

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.

Drug: Favipiravir (3200 mg + 1200 mg) combined with Hydroxychloroquine

Favipiravir combined with Azithromycin

EXPERIMENTAL

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.

Drug: Favipiravir (3200 mg + 1200 mg) combined with Azithromycin

Hydroxychloroquine

ACTIVE COMPARATOR

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).

Drug: Hydroxychloroquine

Hydroxychloroquine combined with Azithromycin

ACTIVE COMPARATOR

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).

Drug: Hydroxychloroquine combined with Azithromycin

Interventions

Favipiravir (3200 mg + 1200 mg)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 (3200 mg + 1200 mg)
Favipiravir (3600 mg + 1600 mg)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 (3600 mg + 1600 mg)
Favipiravir (3200 mg + 1200 mg) combined with HydroxychloroquineDRUG

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 Hydroxychloroquine
Favipiravir (3200 mg + 1200 mg) combined with AzithromycinDRUG

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.

Favipiravir combined with Azithromycin
HydroxychloroquineDRUG

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
Hydroxychloroquine combined with AzithromycinDRUG

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).

Hydroxychloroquine combined with Azithromycin

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • Symptoms such as fever, muscle aches, joint pain, cough, sore throat, nasal congestion, however no respiratory distress, no tachypnea or no SpO2 \< 93%,
  • Chest imaging (X-ray or CT chest) documented as normal
  • Patients with mild possible or confirmed COVID-19 pneumonia (no severe pneumonia symptoms):
  • 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,
  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hacettepe University, School of Medicine

Ankara, Turkey (Türkiye)

Location

MeSH Terms

Conditions

COVID-19

Interventions

favipiravirHydroxychloroquineAzithromycin

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

ChloroquineAminoquinolinesQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsErythromycinMacrolidesPolyketidesLactonesOrganic Chemicals

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof.

Study Record Dates

First Submitted

May 23, 2020

First Posted

June 2, 2020

Study Start

May 8, 2020

Primary Completion

December 31, 2020

Study Completion

June 1, 2021

Last Updated

February 1, 2021

Record last verified: 2021-01

Locations

TU(1)