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

NCT04335552 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO00105339
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 4

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

Conditions

SARS-CoV-2

Keywords

COVID-19

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Number of Participants Who Died During the Index Hospitalization

  Index hospitalization, up to 46 days

• Number of Days on Mechanical Ventilation

  Baseline

• 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

• WHO Ordinal Scale Measured at 28 Days After Enrollment

  Day 28

• Hospital Length of Stay in Days for the Index Hospitalization

  Index hospitalization, up to 46 days

Study Arms (4)

Standard of care

ACTIVE COMPARATOR

Other: Standard of care

Standard of care plus hydroxychloroquine

EXPERIMENTAL

Standard of care plus hydroxychloroquine for 5 days

Other: Standard of care; Drug: Hydroxychloroquine

Standard of care plus azithromycin

EXPERIMENTAL

Standard of care plus azithromycin for 5 days

Other: Standard of care; Drug: Azithromycin

Standard of care plus hydroxychloroquine plus azithromycin

EXPERIMENTAL

Standard of care plus hydroxychloroquine plus azithromycin for 5 days

Other: Standard of care; Drug: Hydroxychloroquine; Drug: Azithromycin

Interventions

Standard of care OTHER

Standard of care

Standard of care; Standard of care plus azithromycin; Standard of care plus hydroxychloroquine; Standard of care plus hydroxychloroquine plus azithromycin

Hydroxychloroquine DRUG

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

Standard of care plus hydroxychloroquine; Standard of care plus hydroxychloroquine plus azithromycin

Azithromycin DRUG

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

Standard of care plus azithromycin; Standard of care plus hydroxychloroquine plus azithromycin

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead

Study Sites (4)

Duke Regional Hospital

Durham, North Carolina, 27704, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

Durham VA Medical Center

Durham, North Carolina, 27710, United States

Location

Duke Raleigh Hospital

Raleigh, North Carolina, 27609, United States

Location

MeSH Terms

Conditions

COVID-19

Interventions

Standard of Care; 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)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Jason Stout, MD, MHS
• Organization: Duke University

jason.stout@dm.duke.edu

919-668-0826

Study Officials

• Jason Stout, MD

  Duke University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 3, 2020
• First Posted: April 6, 2020
• Study Start: April 17, 2020
• Primary Completion: June 17, 2020
• Study Completion: June 26, 2020
• Last Updated: May 17, 2021
• Results First Posted: May 12, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)