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

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19; SARS-CoV-2
• Intervention / Treatment: Drug: Hydroxychloroquine Sulfate; Combination product: Hydroxychloroquine Sulfate + Azithromycin

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

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Robert Wood Johnson University Hopsital
    • Newark, New Jersey, United States, 07103
      • The University Hospital
    • Newark, New Jersey, United States, 07112
      • University Hospital-Newark

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: 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.	Drug: Hydroxychloroquine Sulfate; Given PO; Other Names: Plaquenil; Hydroxychloroquine; Combination product: Hydroxychloroquine Sulfate + Azithromycin; Given PO; Other Names: Plaquenil; Z-Pak; Zithromax; Zmax; Hydroxychloroquine
Experimental: Arm 2: Hydroxychloroquine Sulfate alone; • Hydroxychloroquine sulfate 200 mg taken by mouth three (3) times a day for 10 days	Drug: Hydroxychloroquine Sulfate; Given PO; Other Names: Plaquenil; Hydroxychloroquine
No Intervention: Arm 3: Placebo; 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom questionnaire	Time to resolution of symptoms	up to 6 months
Fever assessment	Change in the fever curve resulting in shorter time to afebrile for 48 hours	up to 10 days
Vital Signs - Body Temperature	Body temperature will be measured in degrees Fahrenheit using an automated thermometer which will be provided to the patient 4 times per day.	up to 10 days
Discharge	Time to discharge (If hospitalized)	up to 6 months
Recovery	Time to recovery (back to school, work, etc)	up to 6 months
Assessment of agent toxicity	As measured by standard metrics	up to 10 days
Oropharynx swab sample collections	Collection of Oropharynx swabs for viral load and microbiome analysis	up to 10 days
Blood Sample collections	Collection of blood for viral load and microbiome analysis	up to 10 days
Viral shedding assessment - nasopharyngeal secretions	Decrease in virus shedding in nasopharyngeal secretions such as Ferritin, D-dimer, CRP, Troponin and LDH	up to 10 days
Viral shedding assessment - serology	Decrease in virus shedding in serology such as Ferritin, D-dimer, CRP, Troponin and LDH	up to 10 days
Cytokines in blood	Measurement of cytokines in blood	up to 10 days

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Actual): October 14, 2020
• Study Completion (Actual): October 14, 2020

Study Registration Dates

• First Submitted: March 31, 2020
• First Submitted That Met QC Criteria: April 2, 2020
• First Posted (Actual): April 7, 2020

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: 002011 (Rutgers Cancer Institute of New Jersey); Pro2020000712 (Other Identifier: Rutgers Cancer Institute of New Jersey)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No