ClinicalTrials.gov

History of Changes for Study: NCT04358068
Evaluating the Efficacy of Hydroxychloroquine and Azithromycin to Prevent Hospitalization or Death in Persons With COVID-19
Latest version (submitted April 20, 2021) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 April 20, 2020 None (earliest Version on record)
2 April 28, 2020 Study Description, Eligibility, Outcome Measures, Arms and Interventions and Study Status
3 May 8, 2020 Recruitment Status, Study Status and Contacts/Locations
4 May 15, 2020 Contacts/Locations and Study Status
5 May 22, 2020 Contacts/Locations and Study Status
6 May 29, 2020 Contacts/Locations and Study Status
7 June 5, 2020 Study Status and Contacts/Locations
8 June 12, 2020 Contacts/Locations and Study Status
9 June 15, 2020 Eligibility and Study Status
10 June 19, 2020 Recruitment Status, Contacts/Locations and Study Status
11 June 25, 2020 Study Status, Outcome Measures, Eligibility, Study Design and Study Description
12 July 17, 2020 Recruitment Status, Study Status and Study Design
13 July 30, 2020 Documents and Study Status
14 February 24, 2021
Quality Control Review has not concluded Returned: March 8, 2021
Recruitment Status, Outcome Measures, Study Status, Study Description, Documents, IPDSharing, References and Eligibility
15 March 11, 2021
Quality Control Review has not concluded Returned: March 18, 2021
Outcome Measures, Reported Adverse Events, Study Status and Baseline Characteristics
16 March 24, 2021 Reported Adverse Events, Study Status
17 April 8, 2021 Study Status and IPDSharing
18 April 20, 2021 Study Status
Comparison Format:

Scroll up to access the controls

Changes (Merged) for Study: NCT04358068
June 5, 2020 (v7) -- June 25, 2020 (v11)

Changes in: Study Status, Study Description, Study Design, Outcome Measures, Eligibility and Contacts/Locations

Open or close this module Study Identification
Unique Protocol ID: ACTG A5395
Brief Title: Evaluating the Efficacy of Hydroxychloroquine and Azithromycin to Prevent Hospitalization or Death in Persons With COVID-19
Official Title: A Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy of Hydroxychloroquine and Azithromycin to Prevent Hospitalization or Death in Persons With COVID-19
Secondary IDs: 38720 [DAIDS-ES Registry Number]
Open or close this module Study Status
Record Verification: June 2020
Overall Status: Active, not recruiting
Study Start: May 1, 2020
Primary Completion: October 9 July 6, 2020 [Anticipated]
Study Completion: March 5 July 6, 2021 2020 [Anticipated]
First Submitted: April 20, 2020
First Submitted that
Met QC Criteria:
April 20, 2020
First Posted: April 22, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
June 5 25, 2020
Last Update Posted: June 9 29, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Responsible Party: Sponsor
Collaborators: Teva Pharmaceuticals Industries LTD
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: The purpose of this study is 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:

This Phase IIB study will 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 will be randomized 1:1 to receive active/placebo study treatment as follows: HCQ/Placebo 400 mg orally twice a day on Day 0 followed by 200 mg orally twice a day for 6 days, and Azithro/Placebo 500 mg once on Day 0, followed by 250 mg daily for 4 days.

Stratification will be by "high" versus "low" risk of progression to severe COVID-19, where "high risk" is defined as a person age ≥60 years or having at least one of several specified comorbidities.

Participants will receive study treatment for 7 days and will be followed for an additional 23 weeks 13 days. Assessments on a subset of 200 participants will include blood collection, self-collected nasal swabs, and nasopharyngeal swabs.

Open or close this module Conditions
Conditions: COVID-19
SARS-CoV 2
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 2000 20 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: 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).

Drug: Hydroxychloroquine (HCQ)
Administered orally
Drug: Azithromycin (Azithro)
Administered orally
Placebo Comparator: 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).

Drug: Placebo for Hydroxychloroquine
Administered orally
Drug: Placebo for Azithromycin
Administered orally
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Proportion of participants who died from any cause or were hospitalized
Hospitalization is 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 is not considered a hospitalization.

[Time Frame: Measured during the 21- 20-day period from and including the day of the first (confirmed) dose of study treatment]
Secondary Outcome Measures:
2. Proportion of participants who died from any cause
Measured during the 21- 20-day period from and including the day of the first (confirmed) dose of study treatment
3. Proportion of participants who died from any cause, or were hospitalized, or had an urgent visit to emergency room or clinic
Measured during the 21- 20-day period from and including the day of the first (confirmed) dose of study treatment
4. Proportion of participants who died from any cause or were hospitalized through the end of follow-up
Hospitalization is 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 is not considered a hospitalization.

[Time Frame: Measured during the 24-week 20-day period from and including the day of the first (confirmed) dose of study treatment]
5. Proportion of participants who prematurely discontinue study treatment due to an adverse event
Measured through Day 7
6. Proportion of participants who had any cardiac adverse events
Measured from start of study treatment through Day 20
7. Duration of Fever
Defined as the last day in the participant's daily diary card on which a temperature greater than 100.4°F was recorded or a potentially antipyretic drug, such as acetaminophen or ibuprofen, was taken.

[Time Frame: Measured through Day 20]
8. Duration of Symptoms Associated With COVID-19 Disease
Defined as the last day in the participant's daily diary card on which a moderate or worse symptom was recorded

[Time Frame: Measured through Day 20]
9. Participant-specific Area Under the Curve (AUC) of the Symptom Score Associated With COVID-19 Disease Over Time
Defined as the sum of scores for the targeted symptoms (defined in the protocol) in the participant's daily diary record (each individual symptom is scored from 0 to 3).

[Time Frame: Measured through Day 20]
10. Time to Self-reported Return to Usual (Pre-COVID) Health.
Measured through Day 20
11. SARS-CoV-2 RNA Detection Status From Self-collected Nasal and Site-collected NP Swabs Among Subset
Measured at entry, Day 6, and Day 20
12. SARS-CoV-2 RNA Level (Continuous) From Self-collected Nasal and Site-collected NP Swabs Among Subset
Measured at entry, Day 6, and Day 20
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Documentation of confirmed active severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection.
  • Experiencing at least one of the following SARS-CoV-2 infection symptoms within 24 hours of screening : fever ( can symptom(s) must be subjective) new or cough OR shortness of breath. 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
  • Agrees 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 21 20 days, whichever is earliest.
  • Agrees 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 using antiarrhythmics within the past 30 days.
  • 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.
  • Use of 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.
  • Participating in a study where co-enrollment is 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
Open or close this module Contacts/Locations
Study Officials: Davey Smith, MD
Study Chair
University of California, San Diego
Locations: United States, Alabama
Alabama CRS
[Recruiting]
Birmingham, Alabama, United States, 35294
Contact:Contact: Faye Heard, M.P.H. 205-996-4405 fhoward@uabmc.edu
Alabama CRS
Birmingham, Alabama, United States, 35294
United States, California
UCLA CARE Center CRS
[Recruiting]
Los Angeles, California, United States, 90025
Contact:Contact: Aleen Khodabakhshian 310-557-9027 akhodabakhshian@mednet.ucla.edu
University of Southern California CRS
[Recruiting]
Los Angeles, California, United States, 90033-1079
Contact:Contact: Luis M. Mendez 323-343-8283 lmendez@usc.edu
United States, California
UCSD Antiviral Research Center CRS
[Recruiting]
San Diego, California, United States, 92103
Contact:Contact: Steven Hendrickx, R.N. 619-543-6968 smhendrickx@ucsd.edu
Ucsf Hiv/Aids Crs
[Recruiting]
San Francisco, California, United States, 94110
Contact:Contact: John Dwyer 415-476-4082 Ext. 353 Jay.Dwyer@ucsf.edu
Harbor-UCLA CRS
[Recruiting]
Torrance, California, United States, 90502
Contact:Contact: Mario Guerrero 424-201-3000 Ext. 7318 mguerrero@labiomed.org
Harbor-UCLA CRS
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Hospital CRS
[Recruiting]
Aurora, Colorado, United States, 80045
Contact:Contact: Suzanne Fiorillo, M.S.P.H. 303-724-5931 suzanne.fiorillo@ucdenver.edu
United States, District of Columbia
Whitman-Walker Health CRS
[Recruiting]
Washington, District of Columbia, United States, 20009
Contact:Contact: Anna Wimpelberg, B.A., CCRC 202-797-3589 AWimpelberg@whitman-walker.org
Whitman-Walker Health CRS
Washington, District of Columbia, United States, 20009
United States, Georgia
The Ponce de Leon Center CRS
[Recruiting]
Atlanta, Georgia, United States, 30308-2012
Contact:Contact: Ericka Patrick, M.S.N. 404-616-6313 erpatri@emory.edu
United States, Illinois
Northwestern University CRS
[Recruiting]
Chicago, Illinois, United States, 60611
Contact:Contact: Baiba Berzins, M.P.H. 312-695-5012 Baiba@northwestern.edu
Northwestern University CRS
Chicago, Illinois, United States, 60611
Rush University CRS
[Recruiting]
Chicago, Illinois, United States, 60612
Contact:Contact: Mark Mall, R.N. 312-942-5865 mark_mall@rush.edu
Rush University CRS
Chicago, Illinois, United States, 60612
United States, Massachusetts
Massachusetts General Hospital CRS (MGH CRS)
[Recruiting]
Boston, Massachusetts, United States, 02114
Contact:Contact: Theresa Flynn, R.N., M.S.N., A.N.P., B.S.N. 617-724-0072 tflynn@partners.org
United States, New Jersey
New Jersey Medical School Clinical Research Center CRS
[Recruiting]
Newark, New Jersey, United States, 07103
Contact:Contact: Rondalya DeShields, R.N., B.S.N. 973-972-3729 deshierd@njms.rutgers.edu
United States, New York
Weill Cornell Chelsea CRS
[Recruiting]
New York, New York, United States, 10010
Contact:Contact: Todd Stroberg, R.N., B.S.N. 212-746-7198 tstrober@med.cornell.edu
Weill Cornell Uptown CRS
[Recruiting]
New York, New York, United States, 10065
Contact:Contact: Rebecca Fry, M.S.N., FNP 212-746-4166 ref2007@med.cornell.edu
University of Rochester Adult HIV Therapeutic Strategies Network CRS
[Recruiting]
Rochester, New York, United States, 14642
Contact:Contact: Christine Hurley 585-210-4136 Christine_Hurley@urmc.rochester.edu
United States, North Carolina
Chapel Hill CRS
[Recruiting]
Chapel Hill, North Carolina, United States, 27599
Contact:Contact: Becky Straub, B.S.N., M.P.H., R.N. 919-843-9975 bstraub@med.unc.edu
United States, North Carolina
Greensboro CRS
[Recruiting]
Greensboro, North Carolina, United States, 27401
Contact:Contact: Kim Epperson, R.N., B.S.N., CRC 336-832-3262 kim.epperson@conehealth.com
Greensboro CRS
Greensboro, North Carolina, United States, 27401
United States, Ohio
Cincinnati Clinical Research Site
[Recruiting]
Cincinnati, Ohio, United States, 45219
Contact:Contact: Sharon Kohrs, R.N., B.S.N. 513-584-6383 kohrssd@ucmail.uc.edu
Cincinnati Clinical Research Site
Cincinnati, Ohio, United States, 45219
Case Clinical Research Site
[Recruiting]
Cleveland, Ohio, United States, 44106
Contact:Contact: Jane Baum, R.N. 216-844-2546 jb@clevelandactu.org
Ohio State University CRS
[Recruiting]
Columbus, Ohio, United States, 43210
Contact:Contact: Kathy Watson, B.S.N., R.N. 614-293-5856 kathy.watson@osumc.edu
United States, Pennsylvania
Penn Therapeutics, CRS
[Recruiting]
Philadelphia, Pennsylvania, United States, 19104
Contact:Contact: Eileen B. Donaghy, C.R.N.P. 215-349-8092 eileen.donaghy2@uphs.upenn.edu
United States, Pennsylvania
University of Pittsburgh CRS
[Recruiting]
Pittsburgh, Pennsylvania, United States, 15213
Contact:Contact: Dawn R. Weinman 412-383-1748 drw38@pitt.edu
United States, Rhode Island
The Miriam Hospital Clinical Research Site (TMH CRS) CRS
[Recruiting]
Providence, Rhode Island, United States, 02906
Contact:Contact: Pamela Poethke, R.N. 401-793-4971 ppoethke@lifespan.org
United States, Tennessee
Vanderbilt Therapeutics (VT) CRS
[Recruiting]
Nashville, Tennessee, United States, 37204
Contact:Contact: Beverly O. Woodward, M.S.N., R.N. 615-936-8516 beverly.o.woodward@vumc.org
United States, Texas
Trinity Health and Wellness Center CRS
[Recruiting]
Dallas, Texas, United States, 75208
Contact:Contact: Lauren Rogers, CCRC 972-807-7370 lauren.rogers@aidsarms.org
United States, Washington
University of Washington AIDS CRS
[Recruiting]
Seattle, Washington, United States, 98104-9929
Contact:Contact: Christine Jonsson, EMBA 206-744-8886 cjonsson@u.washington.edu
Puerto Rico
Puerto Rico AIDS Clinical Trials Unit CRS
[Recruiting]
San Juan, Puerto Rico, 00935
Contact:Contact: Sylvia I. Davila Nieves, M.Sc. 787-767-9192 sylvia.davila1@upr.edu
Open or close this module IPDSharing
Plan to Share IPD: Yes
Individual participant data that underlie results in the publication, after deidentification.
Supporting Information:
Study Protocol
Statistical Analysis Plan (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://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.
URL:
Open or close this module References
Citations:
Links:
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services