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Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection

Primary Purpose

SARS-CoV-2

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Standard of care
Hydroxychloroquine
Azithromycin
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for SARS-CoV-2 focused on measuring COVID-19

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Admitted to participating hospital with symptoms suggestive of COVID-19 infection OR develop symptoms of COVID-19 during hospitalization
  2. Subject (or legally authorized representative) can provide written informed consent (in English or Spanish) affirming intention to comply with planned study procedures prior to enrollment
  3. Male or female adult aged 12 years or older at the time of enrollment
  4. Has laboratory-confirmed SARS-CoV-2 infection determined by a validated nucleic acid amplification assay (public health or commercial) in any respiratory specimen collected within 14 days of randomization

  5. Illness of any duration that includes

    • Radiographic evidence of pulmonary infiltrates (chest X-ray or CT scan) OR
    • Clinical documentation of lower respiratory symptoms (cough, shortness of breath, wheezing) OR
    • Any documented SpO2 ≤ 94% on room air OR
    • Any inpatient initiation or supplemental oxygen regardless of documented cause

Exclusion Criteria:

  1. Participating in any other clinical trial of an experimental agent for COVID-19
  2. On hydroxychloroquine at any time during hospitalization, or within 180 days of hospitalization for COVID-19 regardless of indication
  3. History of G6PD deficiency, cirrhosis, long QT syndrome or porphyria of any classification
  4. Most recent ECG prior to time of screening with QTc of ≥500 msec
  5. Known hypersensitivity to hydroxychloroquine or 4-aminoquinoline derivatives
  6. Death anticipated within 48 hours of enrollment
  7. Inability to obtain informed consent from the patient or designated medical decision maker

Sites / Locations

  • Duke Regional Hospital
  • Duke University Hospital
  • Durham VA Medical Center
  • Duke Raleigh Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Experimental

Experimental

Arm Label

Standard of care

Standard of care plus hydroxychloroquine

Standard of care plus azithromycin

Standard of care plus hydroxychloroquine plus azithromycin

Arm Description

Standard of care plus hydroxychloroquine for 5 days

Standard of care plus azithromycin for 5 days

Standard of care plus hydroxychloroquine plus azithromycin for 5 days

Outcomes

Primary Outcome Measures

World Health Organization (WHO) Ordinal Scale Measured at 14 Days After Enrollment
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

Secondary Outcome Measures

Number of Participants Who Died During the Index Hospitalization
Number of Days on Mechanical Ventilation
Number of Patients Not Receiving Mechanical Ventilation at Baseline Who Progress to Requiring Mechanical Ventilation During the Index Hospitalization
WHO Ordinal Scale Measured at 28 Days After Enrollment
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Hospital Length of Stay in Days for the Index Hospitalization
Number of Participants With All-cause Study Medication Discontinuation
Number of participants who discontinued study medication for any reason
Number of Participants With Severe Adverse Events

Full Information

First Posted
April 3, 2020
Last Updated
May 13, 2021
Sponsor
Duke University
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1. Study Identification

Unique Protocol Identification Number
NCT04335552
Brief Title
Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection
Official Title
Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Terminated
Why Stopped
Poor recruitment, strong evidence from larger trials of no therapeutic benefit
Study Start Date
April 17, 2020 (Actual)
Primary Completion Date
June 17, 2020 (Actual)
Study Completion Date
June 26, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a pragmatic, randomized, open-label, incomplete factorial with nested randomization clinical trial evaluating the efficacy and safety of two potential treatments for hospitalized patients with confirmed SARS-CoV-2 infection. Participants who are hospitalized and have a positive nucleic acid amplification test for SARS-CoV-2 will undergo an initial randomization in a 1:1 ratio to one of the following regimens: Arm 1: Standard of care alone Arm 2: Standard of care plus hydroxychloroquine Participants who meet eligibility criteria to receive azithromycin will undergo a second randomization in a 1:1 ratio to receive additional concurrent therapy. This will effectively result in four treatment groups: Standard of care alone Standard of care plus hydroxychloroquine Standard of care plus azithromycin Standard of care plus hydroxychloroquine plus azithromycin

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SARS-CoV-2
Keywords
COVID-19

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Model Description
Patients will be initially randomized to one of two arms in a 1:1 ratio: 1) Standard of care treatment or 2) Standard of care treatment plus 5 days of hydroxychloroquine. Participants who meet eligibility criteria to receive azithromycin will undergo a second randomization in a 1:1 ratio to receive additional concurrent therapy.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of care
Arm Type
Active Comparator
Arm Title
Standard of care plus hydroxychloroquine
Arm Type
Experimental
Arm Description
Standard of care plus hydroxychloroquine for 5 days
Arm Title
Standard of care plus azithromycin
Arm Type
Experimental
Arm Description
Standard of care plus azithromycin for 5 days
Arm Title
Standard of care plus hydroxychloroquine plus azithromycin
Arm Type
Experimental
Arm Description
Standard of care plus hydroxychloroquine plus azithromycin for 5 days
Intervention Type
Other
Intervention Name(s)
Standard of care
Intervention Description
Standard of care
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
Hydroxychloroquine will be administered orally or via feeding tube at a dosage of 800 mg on day 1, followed by 600 mg daily on days 2-5
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Intervention Description
Azithromycin will be administered orally or via feeding tube at a dosage of 500 mg on day 1, followed by 250 mg daily on days 2-5
Primary Outcome Measure Information:
Title
World Health Organization (WHO) Ordinal Scale Measured at 14 Days After Enrollment
Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Time Frame
Day 14
Secondary Outcome Measure Information:
Title
Number of Participants Who Died During the Index Hospitalization
Time Frame
Index hospitalization, up to 46 days
Title
Number of Days on Mechanical Ventilation
Time Frame
Baseline
Title
Number of Patients Not Receiving Mechanical Ventilation at Baseline Who Progress to Requiring Mechanical Ventilation During the Index Hospitalization
Time Frame
Index hospitalization, up to 46 days
Title
WHO Ordinal Scale Measured at 28 Days After Enrollment
Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Time Frame
Day 28
Title
Hospital Length of Stay in Days for the Index Hospitalization
Time Frame
Index hospitalization, up to 46 days
Title
Number of Participants With All-cause Study Medication Discontinuation
Description
Number of participants who discontinued study medication for any reason
Time Frame
Index hospitalization, up to 46 days
Title
Number of Participants With Severe Adverse Events
Time Frame
Day 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Admitted to participating hospital with symptoms suggestive of COVID-19 infection OR develop symptoms of COVID-19 during hospitalization Subject (or legally authorized representative) can provide written informed consent (in English or Spanish) affirming intention to comply with planned study procedures prior to enrollment Male or female adult aged 12 years or older at the time of enrollment Has laboratory-confirmed SARS-CoV-2 infection determined by a validated nucleic acid amplification assay (public health or commercial) in any respiratory specimen collected within 14 days of randomization Illness of any duration that includes Radiographic evidence of pulmonary infiltrates (chest X-ray or CT scan) OR Clinical documentation of lower respiratory symptoms (cough, shortness of breath, wheezing) OR Any documented SpO2 ≤ 94% on room air OR Any inpatient initiation or supplemental oxygen regardless of documented cause Exclusion Criteria: Participating in any other clinical trial of an experimental agent for COVID-19 On hydroxychloroquine at any time during hospitalization, or within 180 days of hospitalization for COVID-19 regardless of indication History of G6PD deficiency, cirrhosis, long QT syndrome or porphyria of any classification Most recent ECG prior to time of screening with QTc of ≥500 msec Known hypersensitivity to hydroxychloroquine or 4-aminoquinoline derivatives Death anticipated within 48 hours of enrollment Inability to obtain informed consent from the patient or designated medical decision maker
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason Stout, MD
Organizational Affiliation
Duke University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke Regional Hospital
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27704
Country
United States
Facility Name
Duke University Hospital
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Durham VA Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Duke Raleigh Hospital
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27609
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection

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