Clinical Trial For Early SARS-CoV-2 (COVID-19) Treatment

Study Overview
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Brief Summary
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This study is a randomized, double-blinded, and placebo controlled phase III clinical trial which aims to investigate the superiority of hydroxychloroquine, favipiravir or hydroxychloroquine + favipiravir treatment, initiated especially in the early period in the treatment of COVID-19, over the patients being followed up with placebo in adults aged 18 59 Years.

Detailed Description
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This study is a randomized, double-blinded, and placebo controlled phase III clinical trial in in adults aged 18 59 Years. The study was planned as a multicenter, randomized controlled, double-blind, parallel-arm drug study. The purpose of this study is to evaluate the efficacy and safety of hydroxychloroquine, favipiravir, or hydroxychloroquine + favipiravir treatments that were initiated early in patients who were caught during filiation or who were decided to be outpatient due to mild disease findings during hospital admission, after the diagnosis of COVID-19 against patients with placebo. It is planned that the study will be conducted with two separate arms. Study arms are planned as 2:2:2:1 for 320:320:320:160 patients as follows. The dose of Favipiravir has been determined as the standard dose. Hydroxychloroquine will also be given without a loading dose.

Official Title
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Efficacy and Safety of the Use of Hydroxychloroquine, Favipiravir or Hydroxychloroquine + Favipiravir in Early SARS-CoV-2 (COVID-19) Treatment

Conditions
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Covid19

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Favipiravir
* Drug: Favipiravir + Hydroxychloroquine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteers who have understood all the procedures to be applied within the scope of the study protocol and gave their consent. Patients between 18-60 years old. Patients whose symptoms and complaints associated with COVID-19 started within 48 hours. Mild cases whose treatment to be given as outpatient. Although asymptomatic, patients with high CRP (> 20 mg/L) and/or lymphopenia (<1000/mm3) Patients with symptoms such as fever, muscle/joint pain, cough, sore throat, nasal congestion, loss of smell. Patients without serious underlying diseases (cardiovascular diseases, diabetes mellitus, hypertension, cancer, chronic lung diseases, immunosuppressive conditions) Patients with normal chest x-ray and / or chest tomography (no sign of pneumonia) Patients who accept oropharyngeal sample and venous blood collection at regular intervals within the scope of the protocol. Patients who were not involved in any other interventional study. Exclusion Criteria: Patients who do not give their consent in writing after informing. Being under the age of 18 and over the age of 60. Patients with a known history of allergy to one of the study drugs (hydroxychloroquine, favipiravir). Volunteers who the researcher thinks may have problems with adherence to treatment. Volunteers who will have trouble taking medication by mouth due to resistant nausea, vomiting or chronic diarrhea. Patients with chronic liver disease and transaminase (ALT or AST) levels 5 times the higher than the normal level. Patients with heart disease or arrhythmia history. Patients with gout or hyperuricemia. Patients with signs of pneumonia in their lungs. Patients with chronic renal failure (glomerular filtration rate <30). Pregnant or breastfeeding patients.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hydroxychloroquine + Favipiravir<br>Hydroxychloroquine 2x200 mg 5 days and favipiravir 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) | Drug: Favipiravir + Hydroxychloroquine<br>* Favipiravir (1600 mg), as two tablet per day at the first day and then Favipiravir (600 mg) as two tablet per day for the remaining 4-day interval + Hydroxychloroquine (200 mg), as two tablets per day for 5-day interval.<br>* Other names: Favicovir Film Tablet + Hydroxychloroquine sulfate;|
| Active Comparator: Favipiravir + Placebo (Hydroxychloroquine)<br>Favipiravir 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) + Placebo (Hydroxychloroquine ) 2x200 mg (5 days) | Drug: Favipiravir<br>* Favipiravir (1600 mg), as two tablet per day at the first day and then Favipiravir (600 mg) as two tablet per day for the remaining 4-day interval + Placebo [Hydroxychloroquine (200 mg)], as two tablets per day for 5-day interval.<br>* Other names: Favicovir Film Tablet;|
| Active Comparator: Hydroxychloroquine + Placebo (Favipiravir)<br>Hydroxychloroquine 2x200 mg (for 5 days) + placebo (favipiravir) 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) | Drug: Hydroxychloroquine<br>* Hydroxychloroquine (200 mg), as two tablets per day for 5-day interval + Placebo [Favipiravir (1600 mg)], as two tablet per day at the first day and then Favipiravir (600 mg) as two tablet per day for the remaining 4-day interval.<br>* Other names: Hydroxychloroquine sulfate;|
| Placebo Comparator: Placebo (Favipiravir) + Placebo (Hydroxychloroquine)<br>Placebo (favipiravir) 2 x 1600 mg loading, then 4 days 2 x 600 mg maintenance (5 days) + Placebo (Hydroxychloroquine) 2x200 mg (5 days) | Drug: Placebo<br>* Placebo [Favipiravir (1600 mg)], as two tablet per day at the first day and then Placebo Favipiravir (600 mg) as two tablet per day for the remaining 4-day interval + Hydroxychloroquine (200 mg), as two tablets per day for 5-day interval.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Worsening of clinical findings | Worsening of clinical findings such as respiratory distress or persistence of fever, which require hospital admission to begin another treatment (for example, remdesivir, dexamethasone, anti-cytokines, etc.) | During the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete resolution of symptoms and signs | Complete resolution of symptoms and signs | Fifth day after examination | 
| Complete resolution of symptoms and signs | Complete resolution of symptoms and signs | Tenth day after examination | 
| Negative RT-PCR test for SARS-CoV-2 | Negative RT-PCR test for SARS-CoV-2 virus | Tenth day after examination | 
| Determination of IgM, IgG levels for SARS-CoV-2 | Determination of IgM, IgG levels for SARS-CoV-2 virus | Tenth day after examination | 
| Negative RT-PCR test for SARS-CoV-2 | Negative RT-PCR test for SARS-CoV-2 on the 30th day visit | Thirtieth day after examination | 
| Determination of IgM, IgG antibodies | Determination of IgM, IgG antibodies against SARS-CoV-2 | Thirtieth day after examination | 
| Development of signs of pneumonia | Development of signs of pneumonia | During the study | 
| Requirement of respiratory support with oxygen mask | Requirement of respiratory support with oxygen mask | During the study | 
| Requirement of respiratory support with high flow oxygen | Requirement of respiratory support with high flow oxygen | During the study | 
| Requirement of mechanical ventilation | Requirement of mechanical ventilation | During the study | 
| Death | Death | During the study | 
| The rate of discontinuation of treatments due to side effects | The rate of discontinuation of treatments due to side effects (gastrointestinal, allergic skin rash, arrhythmia, other cardiac reasons) | During the study | 
| Time to improvement of symptoms after the initiation of study drugs | Time to improvement of symptoms after the initiation of study drugs | During the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hydroxychloroquine, COVID-19, Favipiravir