Treatment for COVID-19 in High-Risk Adult Outpatients

University of Washington

Status and phase: Terminated; Phase 3; Phase 2

Conditions: COVID-19; SARS-CoV-2

Treatments: Drug: Folic Acid; Drug: Lopinavir 200 MG / Ritonavir 50 MG [Kaletra]; Drug: Azithromycin; Drug: Ascorbic Acid; Drug: Hydroxychloroquine Sulfate

Study type: Interventional

Funder types: Other

Identifiers

NCT04354428

INV-017062 (Other Grant/Funding Number)

STUDY00009878

Details and patient eligibility

About

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.

Full 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.

Enrollment: 289 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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289 participants in 5 patient groups, including a placebo group

Ascorbic acid and Folic acid

Placebo Comparator group

Description:

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)

Treatment:

Drug: Ascorbic Acid

Drug: Folic Acid

Hydroxychloroquine and Folic Acid

Experimental group

Description:

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 \[Days 2 to 5\])

Treatment:

Drug: Hydroxychloroquine Sulfate

Drug: Folic Acid

Hydroxychloroquine and Azithromycin

Experimental group

Description:

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).

Treatment:

Drug: Hydroxychloroquine Sulfate

Drug: Azithromycin

Lopinavir-ritonavir

Experimental group

Description:

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)

Treatment:

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

Ascorbic acid

Placebo Comparator group

Description:

Ascorbic acid 1 gm orally twice on Day 1, followed by 500 mg orally twice daily for 9 days

Treatment:

Drug: Ascorbic Acid