Treatment for COVID-19 in High-Risk Adult Outpatients

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04354428
• Other study ID #: STUDY00009878
• Secondary ID: INV-017062
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: April 16, 2020
• Est. completion date: November 30, 2020

Study information

• Verified date: July 2022
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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

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 information / eligibility

• Status: Terminated
• Enrollment: 289
• Est. completion date: November 30, 2020
• Est. primary completion date: November 3, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2

Intervention

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
• Hydroxychloroquine Sulfate
Eligible participants in a household randomized to this study arm will receive hydrochloroquine and folic acid therapy
• Azithromycin
Eligible participants in a household randomized to this study arm will receive hydrochloroquine and azithromycin therapy
• Folic Acid
Eligible participants in a household will receive folic acid and an additional intervention drug
• Lopinavir 200 MG / Ritonavir 50 MG [Kaletra]
Eligible participants in a household randomized to this study arm will receive lopinavir-ritonavir therapy

Locations

Country	Name	City	State
United States	Boston University	Boston	Massachusetts
United States	Ruth M. Rothstein CORE Center - Cook County Health	Chicago	Illinois
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	SUNY Upstate Medical University	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Bill and Melinda Gates Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	28 days from enrolment
Primary	Number of Participants With Hospitalization or Mortality	Number of participants with hospitalization or mortality	Day 28 after enrolment
Primary	Time to Clearance of Nasal SARS-CoV-2	Time to clearance of nasal SARS-CoV-2, defined as 2 consecutive negative swabs	Day 1 through Day 14 after enrolment
Primary	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.	Day 1 through Day 14 after enrolment
Secondary	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	28 days from enrolment
Secondary	COVID-19-related Hospitalization Days	Duration of hospitalization among persons who become hospitalized with COVID-19 disease	28 days from enrolment