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

NCT ID: NCT04334967

Last Updated: 2020-09-16

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE4
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-30
• Study Completion Date: 2022-05-27

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.

Conditions

COVID-19; Corona Virus Infection; SARS-CoV-2; 2019-nCoV; 2019 Novel Coronavirus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Treatment Arm

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).

Group Type: EXPERIMENTAL

Hydroxychloroquine

Intervention Type: DRUG

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.

Control Arm

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).

Group Type: ACTIVE_COMPARATOR

Vitamin C

Intervention Type: DIETARY_SUPPLEMENT

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.

Interventions

Hydroxychloroquine

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: DRUG

Vitamin C

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.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

ascorbic acid

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.

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Center for Outcomes Research and Education

UNKNOWN

Sponsor Role: collaborator

Providence Cancer Center, Earle A. Chiles Research Institute

OTHER

Sponsor Role: collaborator

Providence Health & Services

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian Kendal, MD

Role: PRINCIPAL_INVESTIGATOR

Providence Medical Group Infectious Disease

Trista Johnson, PhD, MPH

Role: STUDY_DIRECTOR

Providence Ambulatory Quality and Clinical Services

Locations

Portland Providence Medical Center

Portland, Oregon, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 32214079 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32173110 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32171740 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32074550 (View on PubMed)

Novel Coronavirus (2019-nCOV) Situation Report - 1. World Health Organization (WHO), 21 January 2020.

Reference Type: BACKGROUND

Novel Coronavirus disease 2019 (2019-nCOV) Situation Report - 60. World Health Organization (WHO), 19 March 2020.

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 20706626 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32147496 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32150618 (View on PubMed)

Other Identifiers

2020000186

Identifier Type: -

Identifier Source: org_study_id