High-dose Hydroxychloroquine for the Treatment of Ambulatory Patients With Mild COVID-19

This study aims to examine the tolerability of high dose hydroxychloroquine in patients with COVID-19 who are not yet hospitalized, but have risk factors for disease progression and complications.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Hydroxychloroquine

Detailed Description

This is a single arm and single-center tolerability study of high dose HCQ therapy in outpatient adult participants with mild COVID-19. In vitro studies have shown antiviral effects of HCQ against SARS Cov-2, but the clinical outcomes in the disease have been variable. The hypothesis is that targeting high risk patients earlier in the disease course and with a higher dose regimen are both required to see improvement in disease outcome measures in COVID-19. This study aims to prove the tolerability of high dose HCQ in this setting.

Patients are selected based on the identification of risk factors associated with more severe disease outcomes. Investigators will enroll twenty patients and perform a detailed Tele-health interview to ensure they meet eligibility criteria and provide informed consent. 1200 mg hydroxychloroquine daily will be prescribed, in divided doses.The subjects will be required to monitor their temperatures twice daily and a daily telephone call with an investigator will review symptoms of disease and potential side effects of the drug. Subjects can discontinue the medication after five days if they no longer have fever, or take the medication for up to ten days if required for fever resolution.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reem Jan, MBBS BSc; Phone Number: 734-972-7953; Email: rjan@medicine.bsd.uchicago.edu
• Study Contact Backup: Name: Iazsmin Ventura, MD; Email: iazsmin.ventura@uchospitals.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Being tested positive for SARS-Cov-2 in outpatient setting in drive-thru, ED, or ambulatory clinics at the University of Chicago within 72 hours of enrollment.
• Age >18
• Fever >100.4 F by any conventional clinical method (forehead, tympanic, oral, axillary, rectal) within 48h prior to enrollment
• Mild COVID-19, defined as the presence of any symptom consistent with an upper respiratory tract infection, including dry cough, sore throat, nasal congestion, fatigue, myalgia, headaches.

Subjects must meet all the above-mentioned criteria, in addition to at least one of the following criteria:

• Age > 55
• Pre-existing pulmonary disease: airway diseases (asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis), history of active or treated lung cancer, history of pneumectomy, interstitial lung diseases, pulmonary hypertension, sleep apnea.
• Diabetes: uncontrolled or controlled diabetes
• Hypertension
• Chronic kidney disease stage 1-3
• History of cardiovascular disease with an electrocardiogram available to the physician-investigator through the subject's electronical medical record within the past thirty days showing a normal QT interval (QT < 500 ms).
• History of immunosuppression
• Active cancer diagnosis, on palliative treatment or requiring current therapy with antimetabolic agents, immunotherapy or radiotherapy.
• At least one fever every 24 hours for > 72h

Exclusion Criteria:

• Participation in any other clinical trial of an experimental agent treatment for COVID-19
• Current hospitalization
• Known hypersensitivity to hydroxyxhloroquine or chloroquine
• Known chronic kidney disease, stage 4-5, or receiving dialysis
• History of retinal disease
• History of uncontrolled hypertension, defined as systolic blood pressure > 180 mmHg and or diastolic blood pressure > 100 mmHg at the most recent physical medical encounter or by patient report.
• History of QT prolongation (QT > 500 ms) or history of Torsades de Pointes
• History of arrhythmias
• Current use of loop diuretics and potassium supplementation or documented history of hypokalemia.
• Pregnancy and lactation
• Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Current use of any of the following medications: flecainide (Tambocor), amiodarone (Cordarone, Pacerone), digoxin (Digox, Digitek), procainamide (Procan, Procanbid), propafenone (Rythmal), antiepileptic agents (phenytoin, phenobarbital, valproic acid, lamotrigine, topiramate), tamoxifen, tricyclic antidepressants (nortriptyline, amitriptyline, imipramine, clomipramine)
• Inability to monitor body temperature (oral, axillary, tympanic or frontal) at least twice a day from study enrollment day (Day 1) to the end of the study (Day 14).
• Inability to provide informed consent to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydroxychloroquine; Hydroxychloroquine 1200 mg daily administered as 600 mg BID for five days or until fevers abate (maximum ten days of treatment allowed). If patients report gastrointestinal discomfort, the dose will be administered as 400 mg TID.	Drug: Hydroxychloroquine; Tolerability study of HCQ 1200 mg administered daily in divided doses for a duration of 5-10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of High Dose HCQ as measured by Adverse Events	Number of Adverse Events observed in all subjects for the duration of the study	14 days
Tolerability of high dose HCQ as measured by HCQ dose modification and ability to complete course	Number of subjects requiring HCQ dose modifications	14 days
Tolerability of high dose HCQ as measured by discontinuation of HCQ before end of course	Number of subjects that discontinue HCQ	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of hospitalization due to COVID-19 as measured by number of patients hospitalized	Number of patients admitted to hospital during study period	14 days
Time to defervescence as measured in days while on treatment protocol	The number of days to reach first fever normalization (criteria for normalization: temperature < 100.4 F)	14 days
Resolution of other COVID-19 symptoms measured in days while on treatment protocol	Number of days to resolve other symptoms, as assessed by a standardized questionnaire for symptom assessment.	14 days

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Reem Jan, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2020
• Primary Completion (Actual): June 10, 2020
• Study Completion (Actual): June 10, 2020

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 14, 2020
• First Posted (Actual): April 17, 2020

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 21, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: hydroxychloroquine
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: IRB20-0572

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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