Clinical trial NCT04411433: Efficacy and Safety of Hydroxychloroquine and Favipiravir in the Treatment of Mild to Moderate COVID-19
Official title: An Open-Label, Multicenter, Parallel-Group, Randomized, Phase III Study to Evaluate the Efficacy and Safety of Hydroxychloroquine and Favipiravir in the Treatment of Mild to Moderate COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Sars-CoV2
COVID-19
Lead sponsor: Ministry of Health, Turkey
Sponsor class: OTHER_GOV
Collaborators: name: Hacettepe University, Faculty of Medicine
name: Prof. Dr. Cemil Tascıoglu Education and Research Hospital Organization
name: Umraniye Education and Research Hospital
name: SB Istanbul Education and Research Hospital
name: Sultan Abdulhamid Han Training and Research Hospital, Istanbul, Turkey
name: Tepecik Training and Research Hospital
name: Istanbul University - Cerrahpasa
name: Ankara University
name: Ankara City Hospital Bilkent
name: Ankara Training and Research Hospital
name: Ege University Hospital (Application and Research Center)
name: Kocaeli Derince Education and Research Hospital
name: Istanbul University
name: Kayseri City Hospital
First posted: 2020-06-02
Enrollment: 1008
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time to recovery (discharge)
timeFrame: 14 days
measure: Decrease in viral load
timeFrame: 14 days
Secondary outcomes:
measure: Adverse Event (AE), Serious Adverse Event (SAE) and discontinuation of treatment
timeFrame: 14 days
measure: Frequency of occurrence of lymphopenia from baseline
timeFrame: 14 days
measure: Frequency of occurrence of thrombocytopenia from baseline
timeFrame: 14 days
measure: Changes in alanine aminotransferase (ALT) levels from baseline
timeFrame: 14 days
measure: Changes in aspartate aminotransferase (AST) levels from baseline
timeFrame: 14 days
measure: Changes in C-reactive protein (CRP) levels from baseline
timeFrame: 14 days
measure: Changes in level of D-dimer levels from baseline
timeFrame: 14 days
measure: Changes in prothrombin time (PT) values from baseline
timeFrame: 14 days
measure: Changes in partial thromboplastin time (PTT) values from baseline
timeFrame: 14 days
measure: Changes in blood pressure from baseline
timeFrame: 14 days
measure: Changes in respiratory rate from baseline
timeFrame: 14 days
measure: Changes in pulse oxymetry from baseline
timeFrame: 14 days
measure: Changes in fever from baseline
timeFrame: 14 days
Other outcomes:
Locations:
city: Ankara
country: Turkey
facility: Hacettepe University, School of Medicine
Study officials:
References: