SARS-CoV-2Phase 2NCT04335552
Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection
A Phase 2 study testing Hydroxychloroquine and Azithromycin in people with SARS-CoV-2, run by Duke University at 4 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- SARS-CoV-2
- What is being tested?
- Hydroxychloroquine and Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 4 sitesUnited States
- Study dates
- 17 Apr 2020to 26 Jun 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Duke Regional Hospital
Durham, North Carolina, 27704
Duke University Hospital
Durham, North Carolina, 27710
Durham VA Medical Center
Durham, North Carolina, 27710
Duke Raleigh Hospital
Raleigh, North Carolina, 27609
About this study
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
Read more
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
- Conditions
- SARS-CoV-2
- Being tested
- Standard of care, Hydroxychloroquine, Azithromycin
- Keywords
- COVID-19
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of careOther
Standard of care
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
AzithromycinDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Standard of care | Active comparator | Not described Receives: Other: Standard of care |
| Standard of care plus hydroxychloroquine | Experimental | Standard of care plus hydroxychloroquine for 5 days Receives: Other: Standard of care; Drug: Hydroxychloroquine |
| Standard of care plus azithromycin | Experimental | Standard of care plus azithromycin for 5 days Receives: Other: Standard of care; Drug: Azithromycin |
| Standard of care plus hydroxychloroquine plus azithromycin | Experimental | Standard of care plus hydroxychloroquine plus azithromycin for 5 days Receives: Other: Standard of care; Drug: Hydroxychloroquine; Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 14
Secondary outcomes (7)
Number of Participants Who Died During the Index Hospitalization
Measured: Index hospitalization, up to 46 days
Number of Days on Mechanical Ventilation
Measured: Baseline
Number of Patients Not Receiving Mechanical Ventilation at Baseline Who Progress to Requiring Mechanical Ventilation During the Index Hospitalization
Measured: Index hospitalization, up to 46 days
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.
Measured: Day 28
Hospital Length of Stay in Days for the Index Hospitalization
Measured: Index hospitalization, up to 46 days
Number of Participants With All-cause Study Medication Discontinuation
Number of participants who discontinued study medication for any reason
Measured: Index hospitalization, up to 46 days
Number of Participants With Severe Adverse Events
Measured: Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2020
- Study start17 Apr 2020
- Primary completion17 Jun 2020
- Study completion26 Jun 2020
Why it stopped: Poor recruitment, strong evidence from larger trials of no therapeutic benefit
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SARS-CoV-2Studies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- 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)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jason Stout, MD, Principal investigator, Duke University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04335552
- Sponsor's protocol ID
- PRO00105339
- Status last verified
- May 2021
- First submitted
- 3 Apr 2020
- Last updated
- 17 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pragmatic Factorial Trial of Hydroxychloroquine, Azithromycin, or Both for Treatment of Severe SARS-CoV-2 Infection
- ClinicalTrials.gov ID
- NCT04335552
- Acronym / sponsor ID
- PRO00105339
- Conditions
- SARS-CoV-2
- Keywords
- COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor recruitment, strong evidence from larger trials of no therapeutic benefit
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 17 Apr 2020 (actual)
- Primary completion
- 17 Jun 2020 (actual)
- Study completion
- 26 Jun 2020 (actual)
- First posted
- 6 Apr 2020 (actual)
- Results
- Posted 12 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| Standard of care | Active comparator | Other: Standard of care |
| Standard of care plus hydroxychloroquine | Experimental | Other: Standard of care, Drug: HydroxychloroquineStandard of care plus hydroxychloroquine for 5 days |
| Standard of care plus azithromycin | Experimental | Other: Standard of care, Drug: AzithromycinStandard of care plus azithromycin for 5 days |
| Standard of care plus hydroxychloroquine plus azithromycin | Experimental | Other: Standard of care, Drug: Hydroxychloroquine, Drug: AzithromycinStandard of care plus hydroxychloroquine plus azithromycin for 5 days |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard of careStandard of care | Other | Standard of care, Standard of care plus azithromycin, Standard of care plus hydroxychloroquine, Standard of care plus hydroxychloroquine plus azithromycin |
| HydroxychloroquineHydroxychloroquine 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 | Standard of care plus hydroxychloroquine, Standard of care plus hydroxychloroquine plus azithromycin |
| AzithromycinAzithromycin 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 | Drug | Standard of care plus azithromycin, Standard of care plus hydroxychloroquine plus azithromycin |
Primary outcome
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.
7 secondary outcomes
Number of Participants Who Died During the Index Hospitalization
Time frame: Index hospitalization, up to 46 days
Number of Days on Mechanical Ventilation
Time frame: Baseline
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
WHO Ordinal Scale Measured at 28 Days After Enrollment
Time frame: Day 28
Hospital Length of Stay in Days for the Index Hospitalization
Time frame: Index hospitalization, up to 46 days
Number of Participants With All-cause Study Medication Discontinuation
Time frame: Index hospitalization, up to 46 days
Number of Participants With Severe Adverse Events
Time frame: Day 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Stout, MD principal investigator
Duke University Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydroxychloroquine and Azithromycin in people with SARS-CoV-2, run by Duke University at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
World Health Organization (WHO) Ordinal Scale Measured at 14 Days After Enrollment (time frame: Day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2021.