Back to resultsHydroxychloroquine in Patients With Newly Diagnosed COVID-19 Compared to Standard of Care
Primary Purpose
COVID-19, Corona Virus Infection, SARS-CoV-2
Status
Suspended
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Hydroxychloroquine
Vitamin C
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19
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.
Sites / Locations
- Portland Providence Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Treatment Arm
Control Arm
Arm Description
Patients 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).
Patients 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).
Outcomes
Primary Outcome Measures
Total Hospitalization
This outcome will be assessed by comparing the percentages of enrolled patients that are hospitalized in the treatment and control arms.
Total Mechanical Ventilation
This outcome will be assessed by comparing the percentages of enrolled patients that have received mechanical ventilation in the treatment and control arms.
Secondary Outcome Measures
Fever intensity measure
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.
Fever intensity measure
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.
Fever intensity measure
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.
Fever intensity measure
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.
Shortness of breath measure
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.
Shortness of breath measure
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.
Shortness of breath measure
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.
Shortness of breath measure
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 measure
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.
Changes in daytime cough measure
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.
Changes in daytime cough measure
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.
Changes in daytime cough measure
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.
Changes in nighttime cough measure
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.
Changes in nighttime cough measure
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.
Changes in nighttime cough measure
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.
Changes in nighttime cough measure
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 mortality
Number of enrolled patients who have died within the specified time frame
Full Information
NCT ID
NCT04334967
First Posted
April 2, 2020
Last Updated
September 14, 2020
Sponsor
Providence Health & Services
Collaborators
Center for Outcomes Research and Education, Providence Cancer Center, Earle A. Chiles Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT04334967
Brief Title
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
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Suspended
Why Stopped
suspected unfavorable risk/benefit assessment
Study Start Date
March 30, 2020 (Actual)
Primary Completion Date
May 27, 2021 (Anticipated)
Study Completion Date
May 27, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Providence Health & Services
Collaborators
Center for Outcomes Research and Education, Providence Cancer Center, Earle A. Chiles Research Institute
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, Corona Virus Infection, SARS-CoV-2, 2019-nCoV, 2019 Novel Coronavirus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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.
Masking
Outcomes Assessor
Masking Description
Analysts will be blinded to patient randomization; outcome data analyses will be conducted with patient identifiers removed.
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
Patients 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).
Arm Title
Control Arm
Arm Type
Active Comparator
Arm Description
Patients 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).
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
Treatment arm medication will be administered on an outpatient basis. Due to the emergent health crisis, study drug will be delivered to patients by institution staff or contract courier using a non-contact protocol.
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin C
Other Intervention Name(s)
ascorbic acid
Intervention Description
Control arm supplement will be administered on an outpatient basis. Due to the emergent health crisis, study supplies will be delivered to patients by institution staff or contract courier using a non-contact protocol.
Primary Outcome Measure Information:
Title
Total Hospitalization
Description
This outcome will be assessed by comparing the percentages of enrolled patients that are hospitalized in the treatment and control arms.
Time Frame
14 days
Title
Total Mechanical Ventilation
Description
This outcome will be assessed by comparing the percentages of enrolled patients that have received mechanical ventilation in the treatment and control arms.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Fever intensity measure
Description
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.
Time Frame
2 days
Title
Fever intensity measure
Description
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.
Time Frame
5 days
Title
Fever intensity measure
Description
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.
Time Frame
10 days
Title
Fever intensity measure
Description
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.
Time Frame
14 days
Title
Shortness of breath measure
Description
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.
Time Frame
2 days
Title
Shortness of breath measure
Description
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.
Time Frame
5 days
Title
Shortness of breath measure
Description
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.
Time Frame
10 days
Title
Shortness of breath measure
Description
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.
Time Frame
14 days
Title
Changes in daytime cough measure
Description
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.
Time Frame
2 days
Title
Changes in daytime cough measure
Description
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.
Time Frame
5 days
Title
Changes in daytime cough measure
Description
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.
Time Frame
10 days
Title
Changes in daytime cough measure
Description
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.
Time Frame
14 days
Title
Changes in nighttime cough measure
Description
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.
Time Frame
2 days
Title
Changes in nighttime cough measure
Description
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.
Time Frame
5 days
Title
Changes in nighttime cough measure
Description
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.
Time Frame
10 days
Title
Changes in nighttime cough measure
Description
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.
Time Frame
14 days
Title
Total mortality
Description
Number of enrolled patients who have died within the specified time frame
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian Kendal, MD
Organizational Affiliation
Providence Medical Group Infectious Disease
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Trista Johnson, PhD, MPH
Organizational Affiliation
Providence Ambulatory Quality and Clinical Services
Official's Role
Study Director
Facility Information:
Facility Name
Portland Providence Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
32214079
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.
Results Reference
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PubMed Identifier
32173110
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.
Results Reference
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PubMed Identifier
32171740
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.
Results Reference
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PubMed Identifier
32074550
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.
Results Reference
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Citation
Novel Coronavirus (2019-nCOV) Situation Report - 1. World Health Organization (WHO), 21 January 2020.
Results Reference
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Citation
Novel Coronavirus disease 2019 (2019-nCOV) Situation Report - 60. World Health Organization (WHO), 19 March 2020.
Results Reference
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PubMed Identifier
20706626
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. Erratum In: PLoS Negl Trop Dis. 2012 Jun;6(6). doi:10.1371/annotation/8683caec-b309-46d7-bc47-dc9cc27108e4. PLoS Negl Trop Dis. 2012 Jun;6(6). doi:10.1371/annotation/c5c14905-8792-4d2e-8179-f8c70064e773. PLoS Negl Trop Dis. 2012 Jun;6(6). doi:10.1371/annotation/e00ee8fb-4ab9-46db-be8e-3696bb362db4.
Results Reference
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PubMed Identifier
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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.
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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.
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Hydroxychloroquine in Patients With Newly Diagnosed COVID-19 Compared to Standard of Care
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