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

SARS-CoV-2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04335552
• Other study ID #: PRO00105339
• Status: Terminated
• Phase: Phase 2
• Start date: April 17, 2020
• Est. completion date: June 26, 2020

Study information

• Verified date: May 2021
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: June 26, 2020
• Est. primary completion date: June 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Infection
• SARS-CoV-2

Intervention

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
• 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

Locations

Country	Name	City	State
United States	Duke Regional Hospital	Durham	North Carolina
United States	Duke University Hospital	Durham	North Carolina
United States	Durham VA Medical Center	Durham	North Carolina
United States	Duke Raleigh Hospital	Raleigh	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 14
Secondary	Number of Participants Who Died During the Index Hospitalization		Index hospitalization, up to 46 days
Secondary	Number of Days on Mechanical Ventilation		Baseline
Secondary	Number of Patients Not Receiving Mechanical Ventilation at Baseline Who Progress to Requiring Mechanical Ventilation During the Index Hospitalization		Index hospitalization, up to 46 days
Secondary	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.	Day 28
Secondary	Hospital Length of Stay in Days for the Index Hospitalization		Index hospitalization, up to 46 days
Secondary	Number of Participants With All-cause Study Medication Discontinuation	Number of participants who discontinued study medication for any reason	Index hospitalization, up to 46 days
Secondary	Number of Participants With Severe Adverse Events		Day 14