Treatment for COVID-19 in High-Risk Adult Outpatients
- Conditions
- SARS-CoV-2COVID-19
- Interventions
- Registration Number
- NCT04354428
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 289
-
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)
- 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)
- 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 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lopinavir-ritonavir Lopinavir 200 MG / Ritonavir 50 MG [Kaletra] LPV/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) Ascorbic acid and Folic acid 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) Ascorbic acid and Folic acid Ascorbic 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) Hydroxychloroquine and Folic Acid 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 \[Days 2 to 5\]) Hydroxychloroquine and Folic Acid Hydroxychloroquine Sulfate 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 \[Days 2 to 5\]) Hydroxychloroquine and Azithromycin Hydroxychloroquine Sulfate 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). Hydroxychloroquine and Azithromycin 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). Ascorbic acid Ascorbic Acid Ascorbic acid 1 gm orally twice on Day 1, followed by 500 mg orally twice daily for 9 days
- Primary Outcome Measures
Name Time Method 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 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
Number of Participants With Hospitalization or Mortality Day 28 after enrolment Number of participants with hospitalization or mortality
Time to Clearance of Nasal SARS-CoV-2 Day 1 through Day 14 after enrolment Time to clearance of nasal SARS-CoV-2, defined as 2 consecutive negative swabs
Time to Resolution of COVID-19 Symptom Resolution in Days Day 1 through Day 14 after enrolment 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With Serious Adverse Events and Adverse Events Resulting in Treatment Discontinuation 28 days from enrolment Serious adverse events (including death and hospitalization) and adverse events resulting in treatment discontinuation
COVID-19-related Hospitalization Days 28 days from enrolment Duration of hospitalization among persons who become hospitalized with COVID-19 disease
Trial Locations
- Locations (6)
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Tulane University
🇺🇸New Orleans, Louisiana, United States
University of Washington Coordinating Center
🇺🇸Seattle, Washington, United States
UW Virology Research Clinic
🇺🇸Seattle, Washington, United States
Boston University
🇺🇸Boston, Massachusetts, United States
Ruth M. Rothstein CORE Center - Cook County Health
🇺🇸Chicago, Illinois, United States