Coronavirus InfectionPhase 2NCT04342169
University of Utah COVID-19 Hydrochloroquine Trial
A Phase 2 study testing Hydroxychloroquine in people with Coronavirus Infection and Coronavirus, run by University of Utah at 1 site in United States.
Trial summary
A novel coronavirus, SARS-CoV-2, is responsible for a rapidly spreading pandemic that has reached 160 countries, infecting over 500,000 individuals and killing more than 24,000 people. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronavirus Infection, Coronavirus, Infectious Disease
- What is being tested?
- Hydroxychloroquine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 368 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Apr 2020to 15 Nov 2021
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient age ≥18 years, competent to provide consent
- Within 48 hours of positive nucleic acid test for SARS-CoV-2
Who cannot join
- Patient already prescribed chloroquine or hydroxychloroquine
- Allergy to hydroxychloroquine
- History of bone marrow or solid organ transplant
- Known G6PD deficiency
- Chronic hemodialysis, peritoneal dialysis, continuous renal replacement therapy or Glomerular Filtration Rate < 20ml/min/1.73m2
- Known liver disease (e.g. Child Pugh score ≥ B or AST>2 times upper limit)
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- Psoriasis
- Porphyria
- Known cardiac conduction delay (QTc > 500mSec) or taking any prescription medications known to prolong QT interval
- Concomitant use of digitalis, flecainide, amiodarone, procainamide, or propafenone
- Seizure disorder
- Prisoner
- Weight < 35kg
- Inability to follow-up - no cell phone or no address or not Spanish or English speaking
- Receipt of any experimental treatment for SARS-CoV-2 (off-label, compassionate use, or trial related) within the 30 days prior to the time of the screening evaluation
- Patient or another member of patient's household has been already enrolled in this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hydroxychloroquine for Outpatients With Confirmed COVID-19
A novel coronavirus, SARS-CoV-2, is responsible for a rapidly spreading pandemic that has reached 160 countries, infecting over 500,000 individuals and killing more than 24,000 people. SARS-CoV-2 causes an acute and potentially lethal respiratory illness, known as COVID-19, that is threatening to overwhelm health care systems due to a dramatic surge in hospitalized and critically ill patients. Patients hospitalized with COVID-19 typically have been symptomatic for 5-7 days prior to admission, indicating that there is a window during which an effective intervention could significantly alter the course of illness, lessen disease spread, and alleviate the stress on hospital resources.
There is no known treatment for COVID-19, though in vitro and one poorly controlled study have identified a potential antiviral activity for HCQ. The rationale for this clinical trial is to measure the efficacy and safety of hydroxychloroquine for reducing viral load and shedding in adult outpatients with confirmed COVID-19.
Read the detailed description
Background COVID-19 is pandemic with high mortality among hospitalized patients despite a benign course in the large majority of patients infected. Limited data are available from small outpatient studies and have not shown efficacy in preventing hospitalization. Hydroxychloroquine (HCQ) and chloroquine have antiviral and immune-modulating effects, but there are no data concerning their efficacy in reducing viral load and shedding in outpatients.
Evidence supporting possible efficacy for hydroxychloroquine. In cell models, chloroquine both interferes with terminal glycosylation of the ACE2 receptor (the cell surface receptor by which SARS-CoV2 enters human cells) and increases endosomal pH, which interferes (at least in vitro) with a crucial step in viral replication.1,2 HCQ is 5x more potent than chloroquine in a Vero cell model of SARS-CoV-2 infection. In independent experiments, chloroquine has confirmed in vitro activity against SARS-CoV-2. Additionally, HCQ has in vitro efficacy against SARS-CoV-1. According to news releases, an as-yet-unpublished set of case series in China (N reportedly 120) suggests the possibility of rapid viral clearance and low rates of progression to critical illness. In addition to in vitro anti-viral effects chloroquine and HCQ appear to have immune-modulatory effects, especially via suppression of release of TNF and IL6, especially in macrophages.
Evidence against efficacy for hydroxychloroquine. Chloroquine and HCQ have been promoted as extremely broad anti-infective agents for decades. The reported effects include suppression of fungi, atypical bacteria, and viruses. Other than the effects on ACE2 glycosylation, the mechanisms invoked as evidence for efficacy against SARS-CoV-2 have also been invoked for a wide range of viruses. However, when chloroquine and HCQ have been studied in humans, neither agent has demonstrated consistent efficacy in clinical trials, including in HIV, influenza, hepatitis, and Dengue. In one trial, chloroquine resulted in increased viral replication in Chikungunya virus [Roques et al, Viruses 2018 May 17;10(5)] while in another hydroxychloroquine was associated with increased HIV viral load [Paton et al, JAMA 2012 Jul 25;308(4):353]. Expert opinion advises against HCQ for MERS, another serious coronavirus. An underpowered (n=30) study of HCQ in COVID-19 recently published in China did not demonstrate any clinical benefit [Chen et al, J Zhejiang University, 2020 March 9]. The long history of clinical failure despite in vitro anti-viral activity suggests a low probability of efficacy.
Rationale for Trial There is significant publicity concerning the potential use of HCQ in this pandemic, and many patients are seeking access to this unproven therapy. The ANZICS guidelines emphasize that novel treatments should be administered within clinical trials; the Surviving Sepsis Campaign guidelines (http://bit.ly/SSCCOVID-19) also affirm the lack of evidence to support the clinical use of (hydroxy)chloroquine. WHO guidance (https://apps.who.int/iris/bitstream/handle/10665/331446/WHO-2019-nCoV-clinical-2020.4-eng.pdf) also strongly affirms that "investigational anti-COVID-19 therapeutics should be done under ethically approved, randomized, controlled trials." The evidence thus strongly favors equipoise.
- Conditions
- Coronavirus Infection, Coronavirus, Infectious Disease
- Being tested
- Hydroxychloroquine, Placebo oral tablet
- Keywords
- coronavirus, COVID-19, hydrochloroquine, placebo
- Medical subject headings
- Coronavirus Infections, Communicable Diseases, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days
Placebo oral tabletDrug
Placebo to be taken on the same schedule as HCQ.
| Study group | Role | What they receive |
|---|---|---|
| HCQ | Experimental | Participants randomized to the HCQ arm will receive HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days. The drug dose (2.4 gm over 5 days) falls at the lower end of doses proposed in various international trials, but it has proven in vitro efficacy, with a ratio of lung tissue trough concentrations to the EC50 (effective concentration to suppress 50% of viral activity) of >20. Receives: Drug: Hydroxychloroquine |
| Placebo | Placebo comparator | Those randomized to placebo will receive a placebo to be taken on the same schedule. Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of Viral Shedding
Duration of viral shedding, as defined by time from randomization to the first of two consecutive negative swabs, measured on days 1 - 14.
Measured: Days
Secondary outcomes (4)
Duration of COVID-19-attributable Symptoms
Duration of COVID-19 symptoms (through DayA15):
this is an integer-valued outcome which is defined as date of first asymptomatic date through the start date.
To determine the end date, first each symptom assessment from baseline through DayA15, inclusive, will be classified as symptomatic, asymptomatic, or unknown.
A symptomatic day is one in which at least one of the core symptoms is observed to exceed the permissible threshold: not experiencing for fever and chills; extremely mild for shortness of breath, diarrhea, and muscle aches; mild for cough and tiredness. If at most one symptom level is missing on a given day and all observed core symptoms' levels are at or below the permissible threshold, the day will be classified as asymptomatic. Otherwise (i.e. if at most five of the core symptoms have a reported symptom level and none of the reported symptom levels exceeded the threshold), the day will be considered unknown.
Measured: Days 1-15
Hospitalization
Outcome is summarized by treatment received; all other summaries show treatment assigned
Measured: within 14 days of enrollment
Number of Participants With Viral Shedding on Day 28
The definition of the persistence of viral shedding on Day 28 outcome relies heavily on the Day 28 swab and is limited to those who have a test result for the Day 28 swab or who are not known to have died on or before DayR + 30 (there is a 2 day window for collecting the Day 28 swab). If the Day 28 swab result is known, the result will be used to define the outcome ("yes" if positive, "no" if negative). Otherwise, subjects with a confirmed cessation of viral shedding when considering daily swab results from DayR + 1 to DayR + 25, inclusive (with the requirement for confirmation waived if the latest available daily result in this interval is negative), and a missing Day 28 value will be assumed to be negative on Day 28; otherwise subjects hospitalized on any of the days DayR + 26{DayR + 30 with a missing Day 28 value will be assumed to be positive on Day 28; otherwise, multiple imputation will be performed.
Measured: Day 28
Adult Household Contact Viral Acquisition
This outcome will be analyzed for households with at least two adults for which no other adult besides the index study subject is positive for COVID-19 at baseline and for which the index study subject is in the ITT population. This binary outcome will be at the household level and will be a "yes" if there is a positive swab by one or more adult household contacts for any of the study-administered swabs from days DayR + 1 to DayR + 14, inclusive. If there are no positive swabs but at least one negative swab, the outcome will be a "no;" otherwise it will be missing.
Measured: Days 1-14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2020
- Study start4 Apr 2020
- Primary completion30 Oct 2021
- Study completion15 Nov 2021
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 Coronavirus InfectionStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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
- Parallel groups
- Model description
- Phase 2, prospective, placebo-controlled, parallel group, randomized trial
- Masking
- None (open label)
- Enrolment
- 368 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adam M. Spivak, MD, University of Utah
- Investigators
- Adam Spivak, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04342169
- Sponsor's protocol ID
- IRB_00131893
- Status last verified
- Jan 2023
- First submitted
- 7 Apr 2020
- Last updated
- 15 Feb 2023
- 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 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxychloroquine for Outpatients With Confirmed COVID-19
- ClinicalTrials.gov ID
- NCT04342169
- Acronym / sponsor ID
- IRB_00131893
- Conditions
- Coronavirus Infection, Coronavirus, Infectious Disease
- Keywords
- coronavirus, COVID-19, hydrochloroquine, placebo
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 368 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- 4 Apr 2020 (actual)
- Primary completion
- 30 Oct 2021 (actual)
- Study completion
- 15 Nov 2021 (actual)
- First posted
- 10 Apr 2020 (actual)
- Results
- Posted 15 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A novel coronavirus, SARS-CoV-2, is responsible for a rapidly spreading pandemic that has reached 160 countries, infecting over 500,000 individuals and killing more than 24,000 people. SARS-CoV-2 causes an acute and potentially lethal respiratory illness, known as COVID-19, that is threatening to overwhelm health care systems due to a dramatic surge in hospitalized and critically ill patients. Patients hospitalized with COVID-19 typically have been symptomatic for 5-7 days prior to admission, indicating that there is a window during which an effective intervention could significantly alter the course of illness, lessen disease spread, and alleviate the stress on hospital resources.
There is no known treatment for COVID-19, though in vitro and one poorly controlled study have identified a potential antiviral activity for HCQ. The rationale for this clinical trial is to measure the efficacy and safety of hydroxychloroquine for reducing viral load and shedding in adult outpatients with confirmed COVID-19.
Detailed description
Background COVID-19 is pandemic with high mortality among hospitalized patients despite a benign course in the large majority of patients infected. Limited data are available from small outpatient studies and have not shown efficacy in preventing hospitalization. Hydroxychloroquine (HCQ) and chloroquine have antiviral and immune-modulating effects, but there are no data concerning their efficacy in reducing viral load and shedding in outpatients.
Evidence supporting possible efficacy for hydroxychloroquine. In cell models, chloroquine both interferes with terminal glycosylation of the ACE2 receptor (the cell surface receptor by which SARS-CoV2 enters human cells) and increases endosomal pH, which interferes (at least in vitro) with a crucial step in viral replication.1,2 HCQ is 5x more potent than chloroquine in a Vero cell model of SARS-CoV-2 infection. In independent experiments, chloroquine has confirmed in vitro activity against SARS-CoV-2. Additionally, HCQ has in vitro efficacy against SARS-CoV-1. According to news releases, an as-yet-unpublished set of case series in China (N reportedly 120) suggests the possibility of rapid viral clearance and low rates of progression to critical illness. In addition to in vitro anti-viral effects chloroquine and HCQ appear to have immune-modulatory effects, especially via suppression of release of TNF and IL6, especially in macrophages.
Evidence against efficacy for hydroxychloroquine. Chloroquine and HCQ have been promoted as extremely broad anti-infective agents for decades. The reported effects include suppression of fungi, atypical bacteria, and viruses. Other than the effects on ACE2 glycosylation, the mechanisms invoked as evidence for efficacy against SARS-CoV-2 have also been invoked for a wide range of viruses. However, when chloroquine and HCQ have been studied in humans, neither agent has demonstrated consistent efficacy in clinical trials, including in HIV, influenza, hepatitis, and Dengue. In one trial, chloroquine resulted in increased viral replication in Chikungunya virus [Roques et al, Viruses 2018 May 17;10(5)] while in another hydroxychloroquine was associated with increased HIV viral load [Paton et al, JAMA 2012 Jul 25;308(4):353]. Expert opinion advises against HCQ for MERS, another serious coronavirus. An underpowered (n=30) study of HCQ in COVID-19 recently published in China did not demonstrate any clinical benefit [Chen et al, J Zhejiang University, 2020 March 9]. The long history of clinical failure despite in vitro anti-viral activity suggests a low probability of efficacy.
Rationale for Trial There is significant publicity concerning the potential use of HCQ in this pandemic, and many patients are seeking access to this unproven therapy. The ANZICS guidelines emphasize that novel treatments should be administered within clinical trials; the Surviving Sepsis Campaign guidelines (http://bit.ly/SSCCOVID-19) also affirm the lack of evidence to support the clinical use of (hydroxy)chloroquine. WHO guidance (https://apps.who.int/iris/bitstream/handle/10665/331446/WHO-2019-nCoV-clinical-2020.4-eng.pdf) also strongly affirms that "investigational anti-COVID-19 therapeutics should be done under ethically approved, randomized, controlled trials." The evidence thus strongly favors equipoise.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase 2, prospective, placebo-controlled, parallel group, randomized trial
| Arm | Type | Receives |
|---|---|---|
| HCQ | Experimental | Drug: HydroxychloroquineParticipants randomized to the HCQ arm will receive HCQ 400mg po BID x 1 day, then 200mg po BID x 4 days. The drug dose (2.4 gm over 5 days) falls at the lower end of doses proposed in various international trials, but it has proven in vitro efficacy, with a ratio of lung tissue trough concentrations to the EC50 (effective concentration to suppress 50% of viral activity) of >20. |
| Placebo | Placebo comparator | Drug: Placebo oral tabletThose randomized to placebo will receive a placebo to be taken on the same schedule. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patient age ≥18 years, competent to provide consent
- Within 48 hours of positive nucleic acid test for SARS-CoV-2
Key exclusion criteria (16 listed)
- Patient already prescribed chloroquine or hydroxychloroquine
- Allergy to hydroxychloroquine
- History of bone marrow or solid organ transplant
- Known G6PD deficiency
- Chronic hemodialysis, peritoneal dialysis, continuous renal replacement therapy or Glomerular Filtration Rate < 20ml/min/1.73m2
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 |
|---|---|---|
| HydroxychloroquineHCQ 400mg po BID x 1 day, then 200mg po BID x 4 days | Drug | HCQ |
| Placebo oral tabletPlacebo to be taken on the same schedule as HCQ. | Drug | Placebo |
Primary outcome
Duration of Viral Shedding
Time frame: Days
Duration of viral shedding, as defined by time from randomization to the first of two consecutive negative swabs, measured on days 1 - 14.
4 secondary outcomes
Duration of COVID-19-attributable Symptoms
Time frame: Days 1-15
Hospitalization
Time frame: within 14 days of enrollment
Number of Participants With Viral Shedding on Day 28
Time frame: Day 28
Adult Household Contact Viral Acquisition
Time frame: Days 1-14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2023.
- 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.
Adam Spivak, MD principal investigator
University of Utah
1 site 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 in people with Coronavirus Infection and Coronavirus, run by University of Utah at 1 site 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 2 inclusion and 16 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: finished, as of the sponsor's last update on 15 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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 15 Feb 2023). 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?
Duration of Viral Shedding (time frame: Days). 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 15 Feb 2023.