A Triple Combination Antiviral Coronavirus Therapy (TriACT) for COVID-19

Study Overview
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Brief Summary
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New outpatient treatments for COVID-19 are urgently needed. There is some evidence that a combination of three medications currently used to treat other viral infections could be effective in fighting this new virus. The purpose of this trial is to evaluate the efficacy of Nitazoxanide (NTZ), Ribavirin (RBV) and Hydroxychloroquine (HCQ) versus placebo in participants with proven SARS-CoV-2 infection The study will enroll 70 participants within the 7 days after having been diagnosed with coronavirus infection. The purpose is to determine if those randomized to 5-day dosing with the three medication combination have decreased viral load and severity of illness in the 10 days following treatment as compared to those taking placebo. Participants will be actively followed for 28 days.

Detailed Description
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Participants will be randomized into one of two treatment plans Triple combination: Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days) Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days) Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days) No active Medication: Placebo administered according to the above schedule Viral load (qPCR via nasal swab) will be assessed at baseline (day 0) as well as at days 3, 6, and 10 to monitor response to antiviral treatment. Immune status will be determined by antibody testing of blood collected at baseline and day 28. Symptom questionnaires will be completed daily for 10 days and day 28.

Official Title
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A Triple Combination Antiviral Coronavirus Therapy (TriACT) RCT Comparing Nitazoxanide, Ribavirin and Hydroxychloroquine vs. Placebo

Conditions
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SARS-CoV Infection, Covid19

Intervention / Treatment
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* Drug: Nitazoxanide
* Drug: Placebo Nitazoxanide
* Drug: Ribavirin
* Drug: Placebo Ribavirin
* Drug: Hydroxychloroquine
* Drug: Placebo Hydroxychloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented SARS-CoV-2 infection by qPCR assay performed within the past 7 days Exclusion Criteria: COVID-19 symptoms requiring hospitalization PO2 < 92% Short of breath at time of enrollment Retinal eye disease Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency Known chronic kidney disease, stage - 5 or receiving dialysis Current use of: Class 3 AAD (amiodarone, dronaderone, dofetilide, sotalol) Class 1A AAD (procainamide, quinidine, disopyramide) Flecainide SSRI: citalopram (Celexa), Escitalopram (Lexapro) chlorpromazine Cilostazol (Pletal) Donepezil (Aricept) Droperidol Fluoconazole Methadone Ondansetron (Zofran) Thioridazine Macrolides (clarithromycin, erythromycin) Fluroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) Tamoxifen Pregnancy or women who are breast feeding Inability to tolerate oral medications Allergy or prior adverse reaction to either hydroxychloroquine sulfate, ribavirin, or nitazoxanide Allergy to adhesives QTc interval > 450 mSEC for men and women History of Torsade de Pointes VT or prior cardiac arrest or congenital long QT interval Non-English-speaking

Ages Eligible for Study
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Minimum Age: 21 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Study Drug<br>5 day dosing of Nitazoxanide, Ribavirin & Hydroxychloroquine sulfate | Drug: Nitazoxanide<br>* Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days)<br>Drug: Ribavirin<br>* Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days)<br>Drug: Hydroxychloroquine<br>* Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days)<br>|
| Placebo Comparator: Placebo<br>5 day dosing of placebo | Drug: Placebo Nitazoxanide<br>* Placebo Nitazoxanide (500 mg po BID for day 1and then 500 mg BID for 4 days)<br>Drug: Placebo Ribavirin<br>* Placebo Ribavirin (600 mg po BID for day 1and then 400 mg BID for 4 days)<br>Drug: Placebo Hydroxychloroquine<br>* Placebo Hydroxychloroquine sulfate (400 mg po BID for day 1 and then 200 mg BID for 4 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Decline in Viral Load Over the 10 Days After Randomization | qPCR measured via nasal swab | 10 days after randomization |