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

Phase 2

Terminated

Interventions: Combination Product: Hydroxychloroquine Sulfate + Azithromycin
Drug: Hydroxychloroquine Sulfate

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

Recruitment & Eligibility

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)

Arm && Interventions

Group	Intervention	Description
Arm 1: Hydroxychloroquine Sulfate + Azithromycin	Hydroxychloroquine Sulfate + Azithromycin	* 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.
Arm 2: Hydroxychloroquine Sulfate alone	Hydroxychloroquine Sulfate	• Hydroxychloroquine sulfate 200 mg taken by mouth three (3) times a day for 10 days
Arm 1: Hydroxychloroquine Sulfate + Azithromycin	Hydroxychloroquine Sulfate	* 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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method

Locations (5): Saint Barnabas Medical Center
🇺🇸
Livingston, New Jersey, United States
Robert Wood Johnson University Hopsital
🇺🇸
New Brunswick, New Jersey, United States
Rutgers Cancer Institute of New Jersey
🇺🇸
New Brunswick, New Jersey, United States
The University Hospital
🇺🇸
Newark, New Jersey, United States
University Hospital-Newark
🇺🇸
Newark, New Jersey, United States