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

NCT04358068 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: ACTG A539538720
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

COVID-19; SARS-CoV 2

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Died From Any Cause or Were Hospitalized

  Hospitalization was defined as requiring at least 24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address needs during the COVID-19 pandemic. Evaluation at a hospital or similar facility with less than 24 hours of acute care was not considered a hospitalization. Formal statistical testing was not conducted due to the small number of participants and events.

  The 20-day period from and including the day of the first dose of study treatment

Secondary Outcomes (12)

• Number of Participants Who Died From Any Cause

  The 20-day period from and including the day of the first dose of study treatment

• Number of Participants Who Died From Any Cause, or Were Hospitalized, or Had an Urgent Visit to Emergency Room or Clinic

  The 20-day period from and including the day of the first dose of study treatment

• Number of Participants Who Died From Any Cause or Were Hospitalized Through the End of Follow-up

  From day of the first dose of study treatment to Week 24

• Number of Participants Who Prematurely Discontinue Study Treatment Due to an Adverse Event

  From start of study treatment through Day 7

• Number of Participants Who Had Any Cardiac Adverse Events

  From start of study treatment through Day 20

Study Arms (2)

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

EXPERIMENTAL

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).

Drug: Hydroxychloroquine (HCQ); Drug: Azithromycin (Azithro)

Arm B: Placebo for Hydroxychloroquine and Azithromycin

PLACEBO COMPARATOR

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).

Drug: Placebo for Hydroxychloroquine; Drug: Placebo for Azithromycin

Interventions

Hydroxychloroquine (HCQ) DRUG

Administered orally

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

Azithromycin (Azithro) DRUG

Administered orally

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

Placebo for Hydroxychloroquine DRUG

Administered orally

Arm B: Placebo for Hydroxychloroquine and Azithromycin

Placebo for Azithromycin DRUG

Administered orally

Arm B: Placebo for Hydroxychloroquine and Azithromycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Teva Pharmaceutical Industries, Ltd.: collaborator

Study Sites (11)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

Harbor-UCLA CRS

Torrance, California, 90502, United States

Location

Whitman-Walker Health CRS

Washington D.C., District of Columbia, 20009, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Rush University CRS

Chicago, Illinois, 60612, United States

Location

Greensboro CRS

Greensboro, North Carolina, 27401, United States

Location

Cincinnati Clinical Research Site

Cincinnati, Ohio, 45219, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

Trinity Health and Wellness Center CRS

Dallas, Texas, 75208, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104-9929, United States

Location

Related Links

• Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected Version 2.1 - July 2017)
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

MeSH Terms

Conditions

COVID-19

Interventions

Hydroxychloroquine; Azithromycin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Limitations and Caveats

The study was terminated early 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.

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• Davey Smith, MD

  University of California, San Diego

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2020
• First Posted: April 22, 2020
• Study Start: May 13, 2020
• Primary Completion: July 8, 2020
• Study Completion: July 8, 2020
• Last Updated: November 16, 2021
• Results First Posted: April 1, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? * To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://submit.mis.s-3.net/ Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Locations

US (11)