Clinical trial NCT04334967: Hydroxychloroquine in Patients With Newly Diagnosed COVID-19 Compared to Standard of Care
Official title: Randomized Study to Evaluate the Safety and Antiviral Efficacy of Hydroxychloroquine in Patients With Newly Diagnosed COVID-19 Compared to Standard of Care Treatment
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE4
Conditions: COVID-19
Corona Virus Infection
SARS-CoV-2
2019-nCoV
2019 Novel Coronavirus
Lead sponsor: Providence Health & Services
Sponsor class: OTHER
Collaborators: name: Center for Outcomes Research and Education
name: Providence Cancer Center, Earle A. Chiles Research Institute
First posted: 2020-04-06
Enrollment: 13
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Upon confirmation of positive nasopharyngeal test for SARS-CoV-2, eligible patients will be randomized 1:1 to either a treatment group or control group.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Total Hospitalization
timeFrame: 14 days
measure: Total Mechanical Ventilation
timeFrame: 14 days
Secondary outcomes:
measure: Fever intensity measure
timeFrame: 2 days
measure: Fever intensity measure
timeFrame: 5 days
measure: Fever intensity measure
timeFrame: 10 days
measure: Fever intensity measure
timeFrame: 14 days
measure: Shortness of breath measure
timeFrame: 2 days
measure: Shortness of breath measure
timeFrame: 5 days
measure: Shortness of breath measure
timeFrame: 10 days
measure: Shortness of breath measure
timeFrame: 14 days
measure: Changes in daytime cough measure
timeFrame: 2 days
measure: Changes in daytime cough measure
timeFrame: 5 days
measure: Changes in daytime cough measure
timeFrame: 10 days
measure: Changes in daytime cough measure
timeFrame: 14 days
measure: Changes in nighttime cough measure
timeFrame: 2 days
measure: Changes in nighttime cough measure
timeFrame: 5 days
measure: Changes in nighttime cough measure
timeFrame: 10 days
measure: Changes in nighttime cough measure
timeFrame: 14 days
measure: Total mortality
timeFrame: 28 days
Other outcomes:
Locations:
city: Portland
country: United States
facility: Portland Providence Medical Center
state: Oregon
Study officials:
affiliation: Providence Medical Group Infectious Disease
name: Brian Kendal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Providence Ambulatory Quality and Clinical Services
name: Trista Johnson, PhD, MPH
role: STUDY_DIRECTOR
References:
citation: CDC COVID-19 Response Team. Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) - United States, February 12-March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):343-346. doi: 10.15585/mmwr.mm6912e2.
citation: Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care. 2020 Jun;57:279-283. doi: 10.1016/j.jcrc.2020.03.005. Epub 2020 Mar 10.
citation: Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents. 2020 May;55(5):105938. doi: 10.1016/j.ijantimicag.2020.105938. Epub 2020 Mar 12.
citation: Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73. doi: 10.5582/bst.2020.01047. Epub 2020 Feb 19.
citation: Novel Coronavirus (2019-nCOV) Situation Report - 1. World Health Organization (WHO), 21 January 2020.
citation: Novel Coronavirus disease 2019 (2019-nCOV) Situation Report - 60. World Health Organization (WHO), 19 March 2020.
citation: Tricou V, Minh NN, Van TP, Lee SJ, Farrar J, Wills B, Tran HT, Simmons CP. A randomized controlled trial of chloroquine for the treatment of dengue in Vietnamese adults. PLoS Negl Trop Dis. 2010 Aug 10;4(8):e785. doi: 10.1371/journal.pntd.0000785.
citation: Touret F, de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res. 2020 May;177:104762. doi: 10.1016/j.antiviral.2020.104762. Epub 2020 Mar 5.
citation: Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Jul 28;71(15):732-739. doi: 10.1093/cid/ciaa237.