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Treatment for COVID-19 in High-Risk Adult Outpatients

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ClinicalTrials.gov Identifier: NCT04354428
Recruitment Status : Recruiting
First Posted : April 21, 2020
Last Update Posted : May 28, 2020
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Christine Johnston, University of Washington

Brief 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) progression among high-risk adult outpatients with SARS-CoV-2 infection to inform public health control strategies.

Condition or disease Intervention/treatment Phase
COVID-19 SARS-CoV-2 Drug: Ascorbic Acid Drug: Hydroxychloroquine Sulfate Drug: Azithromycin Drug: Folic Acid Phase 2 Phase 3

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 in a 1:1:1 ratio to Hydrocychloroquine (HCQ) + placebo (folic acid), HCQ + azithromycin, 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 630 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of Novel Agents for Treatment of SARS-CoV-2 Infection Among High-Risk Outpatient Adults: An Adaptive Randomized Platform Trial
Actual Study Start Date : April 16, 2020
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Folic acid

Arm Intervention/treatment
Placebo Comparator: Ascorbic acid and Folic acid
Ascorbic 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)
Drug: Ascorbic Acid
Eligible participants in a household randomized to this study arm will receive ascorbic acid and folic acid therapy.
Other Name: Placebo

Drug: Folic Acid
Eligible participants in a household will receive folic acid and an additional intervention drug
Other Name: Placebo

Experimental: Hydroxychloroquine and Folic Acid
HCQ 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])
Drug: Hydroxychloroquine Sulfate
Eligible participants in a household randomized to this study arm will receive hydrochloroquine and folic acid therapy
Other Name: Intervention A

Drug: Folic Acid
Eligible participants in a household will receive folic acid and an additional intervention drug
Other Name: Placebo

Experimental: Hydroxychloroquine and Azithromycin
HCQ 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).
Drug: Hydroxychloroquine Sulfate
Eligible participants in a household randomized to this study arm will receive hydrochloroquine and folic acid therapy
Other Name: Intervention A

Drug: Azithromycin
Eligible participants in a household randomized to this study arm will receive hydrochloroquine and azithromycin therapy
Other Name: Intervention B




Primary Outcome Measures :
  1. Lower respiratory tract infection (LRTI) rates [ Time Frame: 28 days from enrolment ]
    Resting blood oxygen saturation (SpO2<93%) level sustained for 2 readings 2 hours apart and presence of subjective dyspnea or cough

  2. Incidence of hospitalization or mortality [ Time Frame: Day 28 after enrolment ]
    Cumulative incidence of hospitalization or mortality

  3. Change in upper respiratory viral shedding [ Time Frame: Day 1 through Day 14 after enrolment ]
    Time to clearance of nasal SARS-CoV-2, defined as 2 consecutive negative swabs


Secondary Outcome Measures :
  1. Rate of participant-reported adverse events [ Time Frame: 28 days from enrolment ]
    Serious adverse events (including death and hospitalization) and adverse events resulting in treatment discontinuation



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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
  • Access to device and internet for Telehealth visits
  • At increased risk of developing severe COVID-19 disease (at least one of the following)

    1. Age ≥60 years
    2. Presence of pulmonary disease, specifically moderate or severe persistent asthma, chronic obstructive pulmonary disease, pulmonary hypertension, emphysema
    3. Diabetes mellitus (type 1 or type 2), requiring oral medication or insulin for treatment
    4. Hypertension, requiring at least 1 oral medication for treatment
    5. Immunocompromised status due to disease (e.g., those living with human immunodeficiency virus with a CD4 T-cell count of <200/mm3)
    6. 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)
    7. Body mass index ≥30 (self-reported)

Exclusion Criteria:

  • 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
  • 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04354428


Contacts
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Contact: Christine Johnston, MD, MPH 206-520-4340 cjohnsto@uw.edu
Contact: Hannah Leingang 206-520-3827 hannal2@uw.edu

Locations
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United States, Illinois
Ruth M. Rothstein CORE Center - Cook County Health Recruiting
Chicago, Illinois, United States, 60612
Contact: Dorothy Rego       Drego@cookcountyhhs.org   
Principal Investigator: Sybil Hosek, PhD         
United States, Louisiana
Tulane University Recruiting
New Orleans, Louisiana, United States, 70118
Contact: Norine Schmidt       nschmid1@tulane.edu   
Principal Investigator: Patricia Kissinger, PhD         
Principal Investigator: Alfred Luk, MD         
United States, Massachusetts
Boston University Recruiting
Boston, Massachusetts, United States, 02215
Contact: Lori Henault       Lori.Henault@bmc.org   
Principal Investigator: Michael Paasche-Orlow, MD         
United States, New York
NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: Stefanie Bendik         
Principal Investigator: Anna Bershteyn, PhD         
SUNY Upstate Medical University Recruiting
Syracuse, New York, United States, 13210
Contact: Michelle Klick       klickm@upstate.edu   
Principal Investigator: Kristopher Paolino, MD         
United States, Washington
University of Washington Coordinating Center Active, not recruiting
Seattle, Washington, United States, 98104
UW Virology Research Clinic Recruiting
Seattle, Washington, United States, 98104
Contact: Kirsten Hauge    206-520-4341    kahauge@uw.edu   
Sponsors and Collaborators
University of Washington
Bill and Melinda Gates Foundation
Investigators
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Principal Investigator: Christine Johnston, MD, MPH University of Washington
  Study Documents (Full-Text)

Documents provided by Christine Johnston, University of Washington:
Study Protocol  [PDF] April 11, 2020
Informed Consent Form  [PDF] April 15, 2020

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Responsible Party: Christine Johnston, Associate Professor, University of Washington
ClinicalTrials.gov Identifier: NCT04354428    
Other Study ID Numbers: STUDY00009878
INV-017062 ( Other Grant/Funding Number: Bill and Melinda Gates Foundation )
First Posted: April 21, 2020    Key Record Dates
Last Update Posted: May 28, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified data from the study will be made available in accordance with the funder's open access policy.
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: Within 3 months of publication of primary results.
Access Criteria: De-identified data from the study will be made available in accordance with the funder's open access policy.
URL: https://www.gatesfoundation.org/how-we-work/general-information/open-access-policy

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Christine Johnston, University of Washington:
Outpatient
Treatment
Additional relevant MeSH terms:
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Folic Acid
Ascorbic Acid
Azithromycin
Hydroxychloroquine
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Hematinics
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antioxidants
Protective Agents