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

Rutgers The State University of New Jersey

Status and phase: Terminated; Phase 2

Conditions: COVID-19; SARS-CoV-2

Treatments: Drug: Hydroxychloroquine Sulfate; Combination Product: Hydroxychloroquine Sulfate + Azithromycin

Study type: Interventional

Funder types: Other

Identifiers

NCT04336332

Pro2020000712 (Other Identifier)

002011

Details and patient eligibility

About

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.

Full 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

Enrollment: 75 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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75 participants in 3 patient groups

Arm 1: Hydroxychloroquine Sulfate + Azithromycin

Experimental group

Description:

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.

Treatment:

Combination Product: Hydroxychloroquine Sulfate + Azithromycin

Drug: Hydroxychloroquine Sulfate

Arm 2: Hydroxychloroquine Sulfate alone

Experimental group

Description:

• Hydroxychloroquine sulfate 200 mg taken by mouth three (3) times a day for 10 days

Treatment:

Drug: Hydroxychloroquine Sulfate

Arm 3: Placebo

No Intervention group

Description:

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