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COVID-19Phase 2/3NCT04354428

Treatment for COVID-19 in High-Risk Adult Outpatients

A Phase 2/3 study testing Ascorbic Acid, Hydroxychloroquine Sulfate and Azithromycin in people with COVID-19 and SARS-CoV-2, run by University of Washington at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a randomized trial for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in high-risk adults not requiring hospital admission.The overarching goal of this study is to assess the effectiveness of interventions on the incidence of lower respiratory tract infection (LRTI)… Read more about this study

Who is it for?
Ages 18 to 80 yearsHealthy volunteers can take part
Conditions the study is for
COVID-19, SARS-CoV-2
What is being tested?
Ascorbic Acid, Hydroxychloroquine Sulfate and Azithromycin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
289 participants
Where
6 sitesUnited States
Study dates
16 Apr 2020to 30 Nov 2020
Phase
Phase 2/3
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 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Men or women 18 to 80 years of age, inclusive, at the time of signing the informed consent
  • Willing and able to provide informed consent
  • Laboratory confirmed SARS-CoV-2 infection, with test results within past 72 hours
  • COVID-19 symptoms, based on the following criteria: At least TWO of the following symptoms: Fever (≥ 38ºC), chills, rigors, myalgia, headache, sore throat, new olfactory and taste disorder(s), OR o At least ONE of the following symptoms: cough, shortness of breath or difficulty breathing (Lopinavir-Ritonavir Platform)
  • Access to device and internet for Telehealth visits
  • At increased risk of developing severe COVID-19 disease (at least one of the following)
Show all 13Show fewer
  • Age ≥60 years
  • Presence of pulmonary disease, specifically moderate or severe persistent asthma, chronic obstructive pulmonary disease, pulmonary hypertension, emphysema
  • Diabetes mellitus (type 1 or type 2), requiring oral medication or insulin for treatment
  • Hypertension, requiring at least 1 oral medication for treatment
  • Immunocompromised status due to disease (e.g., those living with human immunodeficiency virus with a CD4 T-cell count of <200/mm3)
  • Immunocompromised status due to medication (e.g., persons taking 20 mg or more of prednisone equivalents a day, anti-inflammatory monoclonal antibody therapies, or cancer therapies)
  • Body mass index ≥30 (self-reported)

Who cannot join

  • Known hypersensitivity to HCQ or other 4-aminoquinoline compounds
  • Known hypersensitivity to azithromycin or other azalide or macrolide antibiotics
  • Currently hospitalized
  • Signs of respiratory distress prior to randomization, including respiratory rate >24
  • Current medications include HCQ
  • Concomitant use of other anti-malarial treatment or chemoprophylaxis
Show all 21Show fewer
  • History of retinopathy of any etiology
  • Psoriasis
  • Porphyria
  • Chronic kidney disease (Stage IV or receiving dialysis)
  • Known bone marrow disorders with significant neutropenia (polymorphonuclear leukocytes <1500) or thrombocytopenia (<100 K)
  • Concomitant use of digoxin, cyclosporin, cimetidine, amiodarone, or tamoxifen
  • Known cirrhosis
  • Known personal or family history of long QT syndrome
  • History of coronary artery disease with a history of graft or stent
  • History of heart failure, Class 2 or greater using the New York Heart Association functional class
  • Taking medications associated with prolonged QT and known risk of torsades de points. These medications may include some antipsychotic and antidepressant medications. (Lopinavir-Ritonavir Platform)
  • Taking medications associated with prolonged QT such as antipsychotic medications or antidepressants (e.g., citalopram, venlafaxine, and bupropion) and unable to stop during the trial
  • Taking warfarin (Coumadin or Jantoven)
  • Known history of glucose-6-phosphate-dehydrogenase deficiency
  • History of myasthenia gravis

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Boston University

    Boston, Massachusetts, 02215

  • Ruth M. Rothstein CORE Center - Cook County Health

    Chicago, Illinois, 60612

  • Tulane University

    New Orleans, Louisiana, 70118

  • University of Washington Coordinating Center

    Seattle, Washington, 98104

  • UW Virology Research Clinic

    Seattle, Washington, 98104

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

Other trials in United States

About this study

Official title: Efficacy of Novel Agents for Treatment of SARS-CoV-2 Infection Among High-Risk Outpatient Adults: An Adaptive Randomized Platform Trial

This is a randomized trial for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in high-risk adults not requiring hospital admission.The overarching goal of this study is to assess the effectiveness of interventions on the incidence of lower respiratory tract infection (LRTI) progression among high-risk adult outpatients with SARS-CoV-2 infection to inform public health control strategies.

Read the detailed description

This is a randomized, multi-center, placebo-equivalent (ascorbic acid + folic acid)-controlled, blinded platform trial. Eligible participants will be enrolled and randomized to Hydrocychloroquine (HCQ) + placebo (folic acid), HCQ + azithromycin, lopinavir-ritonavir (LPV/r) or placebo (ascorbic acid + folic acid). Initially, this study will enroll up to 495 eligible adults ( with high risk for Lower respiratory tract infection (LRTI) progression at baseline who are PCR-confirmed SARS-CoV-2 infection (165 per arm). An additional cohort of 135 eligible adults without risk factors for LRTI progression at baseline who are PCR-confirmed SARS-CoV-2 infection will be enrolled for the co-primary virologic outcome. During the 28 study days, participants will take the medication, complete surveys, collect mid nasal swab for viral quantification, and assess symptoms for progression to LRTI. Additional arms will be added should new potential agents be discovered or combination treatments be proposed. In addition, arms may be dropped prior to completion if deemed futile or if there is a safety signal.

Conditions
COVID-19, SARS-CoV-2
Being tested
Ascorbic Acid, Hydroxychloroquine Sulfate, Azithromycin, Folic Acid, Lopinavir 200 MG / Ritonavir 50 MG [Kaletra]
Keywords
Outpatient, Treatment, 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.

  • Ascorbic AcidDrug

    Also called Placebo

    Eligible participants in a household randomized to this study arm will receive ascorbic acid only or ascorbic acid and additional drug therapy

  • Hydroxychloroquine SulfateDrug

    Also called Intervention A

    Eligible participants in a household randomized to this study arm will receive hydrochloroquine and folic acid therapy

  • AzithromycinDrug

    Also called Intervention B

    Eligible participants in a household randomized to this study arm will receive hydrochloroquine and azithromycin therapy

  • Folic AcidDrug

    Also called Placebo

    Eligible participants in a household will receive folic acid and an additional intervention drug

  • Lopinavir 200 MG / Ritonavir 50 MG [Kaletra]Drug

    Also called Intervention C

    Eligible participants in a household randomized to this study arm will receive lopinavir-ritonavir therapy

Study groups in NCT04354428
Study groupRoleWhat they receive
Ascorbic acid and Folic acidPlacebo comparatorAscorbic acid 500 mg orally twice on Day 1, followed by 250 mg orally twice daily for 9 days + folic acid 800 µg orally once on Day 1, followed by 400 µg orally once daily for an additional 4 days (Days 2 to 5)
Receives: Drug: Ascorbic Acid; Drug: Folic Acid
Hydroxychloroquine and Folic AcidExperimentalHCQ 400 mg orally twice on Day 1, followed by 200 mg orally twice daily for an additional 9 days (Days 2 to 10) + placebo (folic acid 800 µg orally once on Day 1, followed by 400 µg orally once daily for an additional 4 days [Days 2 to 5])
Receives: Drug: Hydroxychloroquine Sulfate; Drug: Folic Acid
Hydroxychloroquine and AzithromycinExperimentalHCQ 400 mg orally twice on Day 1, followed by 200 mg orally twice daily for an additional 9 days (Days 2 to 10) + azithromycin 500 mg orally once on Day 1, followed by 250 mg orally once daily for an additional 4 days (Days 2 to 5).
Receives: Drug: Hydroxychloroquine Sulfate; Drug: Azithromycin
Lopinavir-ritonavirExperimentalLPV/r 800 mg-200 mg orally twice on Day 1, followed by 400 mg 100 mg orally twice daily for an additional 9 days (Days 2 to 10)
Receives: Drug: Lopinavir 200 MG / Ritonavir 50 MG [Kaletra]
Ascorbic acidPlacebo comparatorAscorbic acid 1 gm orally twice on Day 1, followed by 500 mg orally twice daily for 9 days
Receives: Drug: Ascorbic Acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Persons With Lower Respiratory Tract Infection (LRTI), Defined as Resting Blood Oxygen Saturation (SpO2<93%) Level Sustained for 2 Readings 2 Hours Apart and Presence of Subjective Dyspnea or Cough

    Resting blood oxygen saturation (SpO2<93%) level sustained for 2 readings 2 hours apart and presence of subjective dyspnea or cough

    Measured: 28 days from enrolment

  2. Number of Participants With Hospitalization or Mortality

    Number of participants with hospitalization or mortality

    Measured: Day 28 after enrolment

  3. Time to Clearance of Nasal SARS-CoV-2

    Time to clearance of nasal SARS-CoV-2, defined as 2 consecutive negative swabs

    Measured: Day 1 through Day 14 after enrolment

  4. Time to Resolution of COVID-19 Symptom Resolution in Days

    COVID-19 symptoms are based on the following criteria:

    • At least TWO of the following symptoms: Fever (≥ 38ºC), chills, rigors, myalgia, headache, sore throat, new olfactory and taste disorder(s), OR
    • At least ONE of the following symptoms: cough, shortness of breath or difficulty breathing, OR
    • Severe respiratory illness with at least 1 of the following:
    • Clinical or radiological evidence of pneumonia, OR
    • Acute respiratory distress syndrome (ARDS), OR
    • LRTI, defined by resting SpO2<93% sustained for 2 readings 2 hours apart AND presence of subjective dyspnea or cough Death or COVID-19-related hospitalizations will count as a failure to resolve symptoms.

    Measured: Day 1 through Day 14 after enrolment

Secondary outcomes (2)

  1. Number of Participants With Serious Adverse Events and Adverse Events Resulting in Treatment Discontinuation

    Serious adverse events (including death and hospitalization) and adverse events resulting in treatment discontinuation

    Measured: 28 days from enrolment

  2. COVID-19-related Hospitalization Days

    Duration of hospitalization among persons who become hospitalized with COVID-19 disease

    Measured: 28 days from enrolment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2020
  2. Study start16 Apr 2020
  3. Primary completion3 Nov 2020
  4. Study completion30 Nov 2020

Why it stopped: Low number of events contributing to primary outcome

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
289 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04354428
Sponsor's protocol ID
STUDY00009878
Other IDs
INV-017062
Status last verified
Jul 2022
First submitted
16 Apr 2020
Last updated
8 Aug 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified data from the study will be made available in accordance with the funder's open access policy.

Publications

  • Mayfield JJ, Chatterjee NA, Noseworthy PA, Poole JE, Ackerman MJ, Stewart J, Kissinger PJ, Dwyer J, Hosek S, Oyedele T, Paasche-Orlow MK, Paolino K, Friedman PA, Waters C, Moreno J, Leingang H, Heller KB, Morrison SA, Krows ML, Barnabas RV, Baeten J, Johnston C; COVID-19 Early Treatment Team; Sridhar AR. Implementation of a fully remote randomized clinical trial with cardiac monitoring. Commun Med (Lond). 2021 Dec 20;1:62. doi: 10.1038/s43856-021-00052-w. eCollection 2021.

    PubMed 35604806

  • Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

    PubMed 34473343

  • Johnston C, Brown ER, Stewart J, Karita HCS, Kissinger PJ, Dwyer J, Hosek S, Oyedele T, Paasche-Orlow MK, Paolino K, Heller KB, Leingang H, Haugen HS, Dong TQ, Bershteyn A, Sridhar AR, Poole J, Noseworthy PA, Ackerman MJ, Morrison S, Greninger AL, Huang ML, Jerome KR, Wener MH, Wald A, Schiffer JT, Celum C, Chu HY, Barnabas RV, Baeten JM; COVID-19 Early Treatment Study Team. Hydroxychloroquine with or without azithromycin for treatment of early SARS-CoV-2 infection among high-risk outpatient adults: A randomized clinical trial. EClinicalMedicine. 2021 Mar;33:100773. doi: 10.1016/j.eclinm.2021.100773. Epub 2021 Feb 27.

    PubMed 33681731

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Ascorbic Acid, Hydroxychloroquine Sulfate and Azithromycin in people with COVID-19 and SARS-CoV-2, run by University of Washington at 6 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 13 inclusion and 21 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 8 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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. 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 8 Aug 2022). 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?

Number of Persons With Lower Respiratory Tract Infection (LRTI), Defined as Resting Blood Oxygen Saturation (SpO2<93%) Level Sustained for 2 Readings 2 Hours Apart and Presence of Subjective Dyspnea or Cough (time frame: 28 days from enrolment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04354428, which also lists 3 linked publications.

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 8 Aug 2022.

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