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Hydroxychloroquine in Patients With Newly Diagnosed COVID-19 Compared to Standard of Care

Phase 4
Suspended
Conditions
2019 Novel Coronavirus
SARS-CoV-2
COVID-19
Corona Virus Infection
2019-nCoV
Interventions
Dietary Supplement: Vitamin C
Registration Number
NCT04334967
Lead Sponsor
Providence Health & Services
Brief Summary

This study will assess the efficacy of hydroxychloroquine in reducing the severity of symptoms in patients with COVID-19

Detailed Description

Hydroxychloroquine has primarily been raised as a potential treatment of SARS-Cov-2 based on in vitro antiviral activity. A draft paper was released recently in March by Didier Raoult from Aix-Marseille University in France on a preliminary trial of 36 COVID-19 patients. In this trial, 6 patients were asymptomatic, 22 had upper respiratory symptoms, and 8 had lower respiratory symptoms. Between early and mid-March, they treated 20 of these patients with 600 mg of hydroxychloroquine daily in a hospital setting. Some patient also received the antibiotic azithromycin. 16 patients served as the controls. They observed a significant reduction in viral load in patients with hydroxychloroquine. After 6 days, 70% of the treated patients were considered cured (no virus detected in their samples) compared to 12.5% of controls. All 6 patients who received both hydroxychloroquine and azithromycin were negative for the virus after 6 days. This was an unblinded, non-randomized trial.

Vitamin C has multiple in-vivo effects on immune modulation that may, in sum, limit the development of the cytokine excess associated with critical illness. It is currently being studied in a clinical trial as a treatment for severe SARS-CoV-2 pneumonia in China and recommended as a supplement in standard treatment of COVID-19.

There are no medications currently approved for treatment of COVID-19. Hydroxychloroquine is a known drug with low toxicity that may reduce progression of respiratory symptoms and resulting hospitalizations. This randomized control study will assess its potential as an off-label treatment in reducing the rates of hospitalization and subsequent mechanical ventilation from COVID-19 infection compared to standard of care treatment with Vitamin C. A randomized control trial with placebo is impractical due to the increasing availability of this medication to the public.

Recruitment & Eligibility

Status
SUSPENDED
Sex
All
Target Recruitment
13
Inclusion Criteria
  • Must have positive nasopharyngeal swab for SARS-CoV-2 diagnosed via outpatient testing within the previous 48 hours
  • Age ≥ 45 years
  • Not hospitalized at the time of enrollment
  • Established care with Providence provider
  • Ability to understand a written or electronic informed consent document
  • Reliable access to a computer or smartphone that can facilitate study communications via remote messaging or telephone and willingness to provide daily verbal check ins
Exclusion Criteria
  • Hypersensitivity to chloroquine or hydroxychloroquine
  • History of retinal disease (macular degeneration, diabetic retinopathy, retinal rear/detachment, retinitis pigmentosa)
  • History of seizure disorder
  • History of ventricular tachycardia/fibrillation, history of long-QT syndrome, or ICD
  • Current creatinine clearance <10 ml/min or on hemodialysis (as evidenced in EMR)
  • Known G6PD deficiency
  • Current use of the following medications: digoxin, amiodarone, flecainide, procainamide, oral dapsone. If other meds of concern, route to pharmacist to evaluate
  • Concomitant use of the following only at Pharmacist/Investigator discretion: Abiraterone acetate, agalsidase, conivaptan, dabrafenib, dacomitinib, dapsone (systemic), digoxin, enzalutamide, fexinidazole, flecainide, fusidic acid (systemic), idelalisib, mifepristone, mitotane, pimozide, amiodarone, digoxin, procainamide, propafenone, stiripentol
  • Currently on hospice
  • Women of childbearing potential must not be pregnant, and must avoid becoming pregnant while on treatment and for 30 days following treatment discontinuation. Men must avoid fathering a child while on treatment and for 30 days following treatment discontinuation
  • Any clinical factors such as bleeding, active infection, or psychiatric factors that in the judgment of the investigator would preclude safe participation and compliance with study procedures.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Control ArmVitamin CPatients in the control arm will receive 500 mg oral Vitamin C. Day 1: 1000 mg dose twice (2000 mg total) Days 2-5: 500 mg dose twice (1000 mg total daily).
Treatment ArmHydroxychloroquinePatients in the treatment arm will receive 200 mg oral hydroxychloroquine. Day 1: 400 mg doses twice (800 mg total). Days 2-5: 200 mg dose twice (400 mg total daily).
Primary Outcome Measures
NameTimeMethod
Total Mechanical Ventilation14 days

This outcome will be assessed by comparing the percentages of enrolled patients that have received mechanical ventilation in the treatment and control arms.

Total Hospitalization14 days

This outcome will be assessed by comparing the percentages of enrolled patients that are hospitalized in the treatment and control arms.

Secondary Outcome Measures
NameTimeMethod
Fever intensity measure14 days

Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.

Changes in nighttime cough measure14 days

Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.

Total mortality28 days

Number of enrolled patients who have died within the specified time frame

Shortness of breath measure14 days

Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.

Changes in daytime cough measure14 days

Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.

Trial Locations

Locations (1)

Portland Providence Medical Center

🇺🇸

Portland, Oregon, United States

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