Evaluate the Efficacy and Safety of Oral Hydroxychloroquine, Indomethacin and Zithromax in Subjects With Mild Symptoms of COVID-19

Study Overview
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Brief Summary
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Currently there are no US Food and Drug Administration (FDA)-approved drugs specifically for the treatment of patients with COVID-19. At present, clinical management includes infection prevention and control measures, as well as supportive care, including supplementary oxygen and mechanical ventilatory support when indicated. An array of drugs approved for other indications as well as several investigational drugs are being studied in several hundred clinical trials that are underway across the globe; however, currently there are no clinical trials available to patients in Arizona. This study will determine if a specific drug cocktail can improve clinical outcomes in patients with confirmed Mild SARS-CoV-2

Detailed Description
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COVID-19 has become a massive threat to public health worldwide. Current estimates suggest that the novel coronavirus (SARS-CoV-2) is both highly contagious (estimated reproductive rate, 2-3) and five to fifty-fold more lethal than seasonal influenza (estimated mortality rate, 0.5-5%); therefore, interventions to decrease the incidence and severity of COVID-19 are emergently needed. In Maricopa County there has yet to be a clinical trial to evaluate people who are SARS-CoV-2 positive with mild symptoms. This study will measure the improvement of COVID-19 disease status as measured by time (days) required from initiation of treatment to improvement of clinical status from mild to symptom free on 14 days of a cocktail therapy of Hydroxychloroquine, Indomethacin and Zithromax.

Official Title
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An Open-Label, Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of Oral Hydroxychloroquine, Indomethacin and Zithromax in Subjects Positive With SARS-CoV-2 With Mild Symptoms

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Indomethacin
* Drug: Zithromax Oral Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 18 years of age Willing and able to provide written informed consent prior to performing study procedures Confirmed Sars-CoV2 infection by PCR Have mild symptoms of Sars-CoV2 Must show documentation of Sars-CoV2 to screening visit Must have had recent hematology and chemistry results Must be able to take heart rate daily Must agree to Skype/Facetime daily Must agree to take temperature daily Must agree not to enroll in another study of an investigational agent prior to completion of Day 14 of treatment. Exclusion Criteria: Known to be allergic to research drugs or drug excipients Incapable of providing informed consent Participation in any other clinical trial of an experimental treatment for Sars-CoV2 infection Pregnancy, possible pregnancy or breast feeding Prolonged QT interval (>450) Moderate to severe symptoms of Sars-CoV2 Renal failure Hepatic failure NSAID use

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
Intervention Model: Single Group Assignment
Interventional Model Description: Open label, single arm study
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Hydroxychloroquine|200 mg PO BID 7 days|
|Drug: Indomethacin|50 mg PO TID 14 Days|
|Drug: Zithromax Oral Product|500 mg PO QD 3 Days|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of clinical status | measured by time (days) required from initiation of treatment to improvement of clinical status from mild to symptom free | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of clinical recovery of fever | the time of normalization of fever as measured by daily temperature ( - ≤36.6°C or -axilla, ≤37.2 °C oral or ≤37.8°C rectal or tympanic) | up to 15 days | 
| Time of clinical recovery of cough | the time of alleviation of cough as measured by self reported visual analog scale (VAS) cough scale. 1=no cough, 2-3=cough sometimes, 4-6=have a cough but can still do things, 7-8=persistent cough, prevents from doing things, 9-10=cough presents a great deal of discomfort | up to 28 days | 
| Safety as determined by changes in QTC intervals measured by ECG | to determine the safety of these therapies in combination | up to 15 days | 
| Safety as determined by presence of side effects | to assess the presence or absence of side effects and whether they are tolerable | up to 15 days | 
| Time to improvement | improvement in Wisconsin Upper Respiratory Symptom Survey (WURSS-44) 0 to 7 scale, with 0 = Do not have, 1 = Very mild, 3 = Mild, 5 = Moderate, 7 = Severe | up to 28 days |