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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04335552
Recruitment Status : Recruiting
First Posted : April 6, 2020
Last Update Posted : April 24, 2020
Sponsor:
Information provided by (Responsible Party):
Duke University

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:

  1. Standard of care alone
  2. Standard of care plus hydroxychloroquine
  3. Standard of care plus azithromycin
  4. Standard of care plus hydroxychloroquine plus azithromycin

Condition or disease Intervention/treatment Phase
SARS-CoV-2 Other: Standard of care Drug: Hydroxychloroquine Drug: Azithromycin Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection
Actual Study Start Date : April 17, 2020
Estimated Primary Completion Date : August 1, 2020
Estimated Study Completion Date : August 1, 2020


Arm Intervention/treatment
Active Comparator: Standard of care Other: Standard of care
Standard of care

Experimental: Standard of care plus hydroxychloroquine
Standard of care plus hydroxychloroquine for 5 days
Other: Standard of care
Standard of care

Drug: Hydroxychloroquine
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

Experimental: Standard of care plus azithromycin
Standard of care plus azithromycin for 5 days
Other: Standard of care
Standard of care

Drug: Azithromycin
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

Experimental: Standard of care plus hydroxychloroquine plus azithromycin
Standard of care plus hydroxychloroquine plus azithromycin for 5 days
Other: Standard of care
Standard of care

Drug: Hydroxychloroquine
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

Drug: Azithromycin
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 Measures :
  1. World Health Organization (WHO) ordinal scale measured at 14 days after enrollment [ Time Frame: Day 14 ]
    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 :
  1. Rates of death during the index hospitalization [ Time Frame: Index hospitalization, up to 46 days ]
  2. Number of days on mechanical ventilation for patients who were on mechanical ventilation at baseline [ Time Frame: Baseline ]
  3. Proportion 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 ]
  4. WHO ordinal scale measured at 28 days after enrollment [ Time Frame: Day 28 ]
    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.

  5. Hospital length of stay in days for the index hospitalization [ Time Frame: Index hospitalization, up to 46 days ]
  6. Rates of all-cause study medication discontinuation [ Time Frame: Index hospitalization, up to 46 days ]
  7. Rates of severe adverse events [ Time Frame: Day 14 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04335552


Contacts
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Contact: Jason Stout, MD 919-668-0826 jason.stout@dm.duke.edu

Locations
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United States, North Carolina
Duke Regional Hospital Recruiting
Durham, North Carolina, United States, 27704
Contact: Jason Stout, MD         
Duke University Hospital Recruiting
Durham, North Carolina, United States, 27710
Contact: Jason Stout, MD         
Durham VA Medical Center Not yet recruiting
Durham, North Carolina, United States, 27710
Duke Raleigh Hospital Recruiting
Raleigh, North Carolina, United States, 27609
Contact: Jason Stout, MD         
Sponsors and Collaborators
Duke University
Investigators
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Principal Investigator: Jason Stout, MD Duke University Hospital
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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT04335552    
Other Study ID Numbers: PRO00105339
First Posted: April 6, 2020    Key Record Dates
Last Update Posted: April 24, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Duke University:
COVID-19
Additional relevant MeSH terms:
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Hydroxychloroquine
Infection
Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents