Randomized Comparison of Combination Azithromycin and Hydroxychloroquine vs. Hydroxychloroquine Alone for the Treatment of Confirmed COVID-19

Study Overview
=================
Brief Summary
-----------------
This is a three-arm randomized trial comparing the efficacy of single agent hydroxychloroquine to the combination of hydroxychloroquine and azithromycin, and to a delayed hydroxychloroquine regimen, which will serve as a contemporaneous Day 1-6 supportive care control, in eliminating detectable SARS-CoV-2 on day 6 following the initiation of treatment in order to determine which regimen is more effective.

Detailed Description
-----------------
PRIMARY OBJECTIVE: I. Determine change in viral load at day 6 compared to baseline between two regimens to treat COVID-19 and a contemporaneous control group. SECONDARY OBJECTIVES: I. Time to resolution of symptoms (symptom questionnaire) II. Change in the fever curve resulting in shorter time to afebrile for 48 hours III. Normalization of vital signs IV. Time to discharge (if hospitalized) V. Assessment of agent toxicity as measured by standard metrics VI. Collection of throat swab and blood for viral load, presence of IgM or IgG antibodies VII. If feasible on samples collected for quantitative PCR decrease in virus shedding (in oropharyngeal secretions) VIII. Measures of cytokines in blood including IL6, IL-8, TNF, INF IX. Routine standard of care labs obtained as part of the care of these patients such as differential white count, CRP, troponin and LFTs will be analyzed for correlative trends

Official Title
-----------------
Randomized Comparison of Combination Azithromycin and Hydroxychloroquine vs. Hydroxychloroquine Alone for the Treatment of Confirmed COVID-19

Conditions
-----------------
SARS-CoV-2, COVID-19

Intervention / Treatment
-----------------
* Combination Product: Hydroxychloroquine Sulfate + Azithromycin
* Drug: Hydroxychloroquine Sulfate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with proven SARS-CoV-2 infection by an accepted assay with symptoms consistent with COVID-19 Ability to measure and quantify viral load by quantitative PCR Age 18 to 89 Ability to swallow oral medications Patients must read, understand and sign IRB approved informed consent Exclusion Criteria: Pregnancy or women who are breast feeding Two consecutive negative assays for SARS-CoV-2 infection Patients that lack decision-making capacity will not be approached to participate in this study Inability to tolerate oral medications Allergy or prior adverse reaction to either azithromycin or hydroxychloroquine sulfate QTc interval > 470 mSEC History of ongoing ventricular cardiac dysrhythmias of grade 2 as described by NCI CTCAE 5.0 criteria History of serious ventricular arrhythmia (VT or VF > 3 beats in a row)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Hydroxychloroquine Sulfate + Azithromycin<br>Hydroxychloroquine sulfate 200 mg taken by mouth three (3) times a day for 10 days Azithromycin 500 mg taken by mouth on Day 1, followed by Azithromycin 250 mg taken by mouth once (1) time a day for four (4) days. | Combination Product: Hydroxychloroquine Sulfate + Azithromycin<br>* Given PO<br>* Other names: Zmax;Drug: Hydroxychloroquine Sulfate<br>* Given PO<br>* Other names: Plaquenil;|
| Experimental: Arm 2: Hydroxychloroquine Sulfate alone<br>• Hydroxychloroquine sulfate 200 mg taken by mouth three (3) times a day for 10 days | Drug: Hydroxychloroquine Sulfate<br>* Given PO<br>* Other names: Plaquenil;|
| No Intervention: Arm 3: Placebo<br>Placebo pills Days 1-6. If you still have COVID-19 symptoms you will receive Hydroxychloroquine sulfate 200 mg by mouth three (3) times a day for 10 days | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Patients Viral Load | Will be assessed at day six compared to baseline between hydroxychloroquine sulfate alone and hydroxychloroquine sulfate plus azithromycin to treat COVID-19. | Baseline and day six |