Evaluating the Efficacy of Hydroxychloroquine and Azithromycin to Prevent Hospitalization or Death in Persons With COVID-19

NCT ID: NCT04358068

Last Updated: 2021-11-16

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-13

Study Completion Date

2020-07-08

Brief Summary

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The purpose of this study was to evaluate the efficacy of hydroxychloroquine (HCQ) and azithromycin (Azithro) to prevent hospitalization or death in symptomatic adult outpatients with COVID-19 caused by SARS-CoV-2 infection.

Detailed Description

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This Phase IIB study was designed to evaluate the efficacy of hydroxychloroquine (HCQ) and azithromycin (Azithro) to prevent hospitalization or death in symptomatic adult outpatients with COVID-19 caused by SARS-CoV-2 infection.

Participants were randomized 1:1 to receive active or placebo study treatment. The target sample size was 2000 participants, with approximately 1000 in each arm. Stratification was by "high" versus "low" risk of progression to severe COVID-19, where "high risk" was defined as a person age ≥60 years or having at least one of several specified comorbidities.

Participants were prescribed study treatment for 7 days and were to be followed for an additional 24 weeks. Assessments on a subset of participants were planned to include blood collection, self-collected nasal swabs, and nasopharyngeal swabs.

On June 23, 2020, sites were informed that the study was closing to follow-up due to slow enrollment and lack of community enthusiasm. Follow-up through week 24 was not completed for any participant. Participants were asked to complete the Day 20 visit and then were discontinued from the study. Due to the early termination, enrollment into the specimen collection subset did not occur, and results associated with those specimens are not available. Due to the small number of participants enrolled, some statistical tests were not able to be performed and only descriptive results are provided.

Conditions

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COVID-19 SARS-CoV 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm A: Hydroxychloroquine (HCQ) and Azithromycin (Azithro)

Hydroxychloroquine 400 mg (administered as two 200 mg capsules) orally twice daily for 2 doses starting on Day 0, followed by 200 mg (administered as one 200 mg capsule) orally twice daily for 12 doses (6 days), PLUS:

Azithromycin 500 mg (administered as two 250 mg capsules) orally as a single dose on Day 0, followed by 250 mg (administered as one 250 mg capsule) orally once daily for 4 doses (4 days).

Group Type EXPERIMENTAL

Hydroxychloroquine (HCQ)

Intervention Type DRUG

Administered orally

Azithromycin (Azithro)

Intervention Type DRUG

Administered orally

Arm B: Placebo for Hydroxychloroquine and Azithromycin

Placebo for Hydroxychloroquine (administered as two matching placebo capsules) orally twice daily for 2 doses starting on Day 0, followed by Placebo for HCQ (administered as one 200 mg capsule) orally twice daily for 12 doses (6 days), PLUS:

Placebo for Azithromycin (administered as two matching placebo capsules) orally as a single dose on Day 0, followed by Placebo for Azithromycin (administered as one matching placebo capsule) orally once daily for 4 doses (4 days).

Group Type PLACEBO_COMPARATOR

Placebo for Hydroxychloroquine

Intervention Type DRUG

Administered orally

Placebo for Azithromycin

Intervention Type DRUG

Administered orally

Interventions

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Hydroxychloroquine (HCQ)

Administered orally

Intervention Type DRUG

Azithromycin (Azithro)

Administered orally

Intervention Type DRUG

Placebo for Hydroxychloroquine

Administered orally

Intervention Type DRUG

Placebo for Azithromycin

Administered orally

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Documentation of confirmed active severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection from any respiratory specimen collected ≤7 days from when the first dose of study treatment was expected to be taken.
* Experienced at least one of the following SARS-CoV-2 infection symptoms within 24 hours of screening (symptom(s) must be new or worse compared to pre-COVID-19 health status):

* Fever (can be subjective) or feeling feverish
* Cough
* Shortness of breath or difficulty breathing at rest or with exertion
* Sore throat
* Body pain or muscle pain
* Fatigue
* Headache
* Agreed to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 during the study period up until reaching hospitalization or 20 days, whichever is earliest.
* Agreed to not obtain study medications outside of the A5395 study.

Exclusion Criteria

* Need for hospitalization or immediate medical attention in the clinical opinion of the study investigator.
* History of or current hospitalization for COVID-19.
* History of ventricular arrhythmia or use of antiarrhythmics within 30 days prior to entry.
* Personal or family history of Long QT syndrome.
* History of kidney disease.
* History of ischemic or structural heart disease.
* History of hypokalemia or hypomagnesemia or taking potassium supplementation or magnesium supplementation
* Personal medical history of porphyria, retinopathy, severe hepatic impairment, or glucose-6-phosphate dehydrogenase (G6PD) deficiency.
* Used drugs with possible anti-SARS-CoV-2 activity within 30 days prior to study entry, e.g., remdesivir, lopinavir/ritonavir fixed dose combination, ribavirin, chloroquine, hydroxychloroquine, and azithromycin, or participation in a clinical trial involving any of these drugs whether for treatment or prophylaxis.
* Requirement or expected requirement for a medication that significantly prolongs QT intervals or increases risk for QT prolongation.
* Loop diuretics are exceptions to above exclusion criterion but these cannot be used within 30 days prior to study entry.
* Participated in a study where co-enrollment was not allowed.
* Receipt of a SARS-CoV-2 vaccination prior to study entry.
* Known allergy/sensitivity or any hypersensitivity to components of HCQ, azithromycin, or their formulation.
* More than 10 days of any of the following symptoms attributed to the SARS-CoV-2 infection at study entry:

* Fever (can be subjective) or feeling feverish
* Cough
* Shortness of breath or difficulty breathing at rest or with exertion
* Sore throat
* Body pain or muscle pain
* Fatigue
* Headache
* Chills
* Nasal obstruction or congestion
* Loss of taste or smell
* Nausea or vomiting
* Diarrhea
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Teva Pharmaceutical Industries, Ltd.

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Davey Smith, MD

Role: STUDY_CHAIR

University of California, San Diego

Locations

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Alabama CRS

Birmingham, Alabama, United States

Site Status

UCSD Antiviral Research Center CRS

San Diego, California, United States

Site Status

Harbor-UCLA CRS

Torrance, California, United States

Site Status

Whitman-Walker Health CRS

Washington D.C., District of Columbia, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Rush University CRS

Chicago, Illinois, United States

Site Status

Greensboro CRS

Greensboro, North Carolina, United States

Site Status

Cincinnati Clinical Research Site

Cincinnati, Ohio, United States

Site Status

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, United States

Site Status

Trinity Health and Wellness Center CRS

Dallas, Texas, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Countries

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Puerto Rico United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables

Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected Version 2.1 - July 2017)

https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-events-daids

Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

Other Identifiers

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38720

Identifier Type: OTHER

Identifier Source: secondary_id

ACTG A5395

Identifier Type: -

Identifier Source: org_study_id