FAvipiravir and HydroxyChloroquine Combination Therapy

Study Overview
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Brief Summary
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This study is a randomized, open-label, parallel groups multi-centered trial were participants are assigned to either an intervention arm ( a combination of Favipiravir and Hydroxychloroquin) or standard of care.

Detailed Description
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In this trial, the investigators want to evaluate the efficacy of the combination of Favipiravir and Hydroxychloroquine as potential therapy for moderate and severe cases with COVID -19. Favipiravir which is a new type of RNA-dependent RNA polymerase (RdRp) inhibitor has activity against influenza virus, and Hydroxychloroquine, an analogue of chloroquine, has a clinical safety profile better than that of chloroquine and allows higher daily dose, Chloroquine is a widely used antimalarial that was found to be a potential broad-spectrum antiviral. There is an urgent need to explore therapeutic options for SARS-CoV-2 in order to face the pandemic. The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, the investigators want to prove the effectiveness of the combination as therapy.

Official Title
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A Trial of Favipiravir and Hydroxychloroquine Combination in Adults Hospitalized With Moderate and Severe Covid-19

Conditions
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COVID19

Intervention / Treatment
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* Combination Product: Favipiravir and Hydroxychloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Should be at least 18 years of age Male or nonpregnant female, Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions). Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms with Chest X ray changes that require hospital admission. patients had to be enrolled within 10 days of disease onset Exclusion Criteria: Patients who are pregnant or breastfeeding. Will be transferred to a non-study site hospital or expected to be discharged within 72 hours. Known sensitivity/allergy to hydroxychloroquine or Favipiravir Current use of hydroxychloroquine for another indication Prior diagnosis of retinopathy Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission. Patient with irregular rhythm Patient with a history of heart attack (myocardial infarction) Patient with a family history of sudden death from heart attack before the age of 50 Take other drugs that can cause prolonged QT interval Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract.

Ages Eligible for Study
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Minimum Age: 18 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, open-label, parallel groups were participants are assigned to either an intervention arm or standard of care.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Combination therapy Favipiravir (10 days) + Hydroxychloroquine(5 days) | Combination Product: Favipiravir and Hydroxychloroquine<br>* Route of Administration: Oral (or through Nasogastric tube) Dose: Favipiravir: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days or till hospital discharge) Hydroxychloroquine (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily.<br>* Other names: Avigan;|
| No Intervention: Control<br>Standard of Care Treatment for COVID-19 Infection | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Improvement | The primary endpoint is the time to clinical improvement, defined as the time from the randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral shedding | PCR test negative conversion days from positive to negative. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2