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.
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.
Drug: Ascorbic Acid
Eligible participants in a household randomized to this study arm will receive ascorbic acid only or ascorbic acid and additional drug therapy
Other Name: Placebo
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
Drug: Folic Acid
Eligible participants in a household will receive folic acid and an additional intervention drug
Other Name: Placebo
Drug: Lopinavir 200 MG / Ritonavir 50 MG [Kaletra]
Eligible participants in a household randomized to this study arm will receive lopinavir-ritonavir therapy
Other Name: Intervention C
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
- 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)
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 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
Ruth M. Rothstein CORE Center - Cook County Health
Chicago, Illinois, United States
Tulane University
New Orleans, Louisiana, United States
Boston University
Boston, Massachusetts, United States
SUNY Upstate Medical University
Syracuse, New York, United States
University of Washington Coordinating Center
Seattle, Washington, United States
UW Virology Research Clinic
Seattle, Washington, United States
Christine Johnston, MD, MPH, Principal Investigator
University of Washington