Pre-exposure Prophylaxis for SARS-Coronavirus-2

Phase 3

Completed

• Conditions: Corona Virus Infection; Acute Respiratory Distress Syndrome; COVID-19; ARDS
• Interventions: Other: Placebo; Drug: Hydroxychloroquine

• Registration Number: NCT04328467
• Lead Sponsor: University of Minnesota

Brief Summary

Objective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.

Detailed Description

The current standard of care is observation and quarantine after exposure to COVID-19. There is no approved treatment or prophylaxis for COVID-19.

As of March 6, 2020, the CDC estimates that the transmission of SARS-CoV2 after a U.S. household close contract is 10.5% (95%CI, 2.9 to 31.4%). Among all close contacts, the SARS-CoV2 transmission rate is estimated at 0.45% (95%CI, 0.12 to 1.6%) by the CDC. These estimates are based on monitoring of travel-associated COVID19 cases. Conversely, in a setting with community transmission, the secondary attack rate in China was 35% (95%CI, 27-44%) based on 48 transmissions among 137 persons in 9 index patients.

Chloroquine or Hydroxychloroquine may have antiviral effects against SARS-COV2 which may prevent COVID-19 disease or reduce disease severity. It is not known at what dosing hydroxychloroquine may be effective for pre-exposure prophylaxis.

Study Timeline

• Study First Submitted: 2020-03-27
• Study First Submitted QC: 2020-03-30
• Study First Posted: 2020-03-31
• Study Start: 2020-04-06
• Primary Completion: 2020-07-13
• Study Completion: 2020-07-13
• Status Verified: 2021-06
• Results First Submitted: 2021-06-25
• Results First Submitted QC: 2021-06-25
• Results First Posted: 2021-06-30
• Last Update Submitted: 2021-06-30
• Last Update Posted: 2021-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1483

Inclusion Criteria

• A healthcare worker at high risk for COVID-19 exposure (defined below):

• Persons primarily working in emergency departments (physicians, nurses, ancillary staff, triage personnel)
• Persons primarily working in intensive care units (physicians, nurses, ancillary staff, respiratory therapists)
• Persons performing aerosol generating procedures (i.e. anesthesiologists, nurse anesthetists (CRNAs)
• First responders (i.e. EMTs, paramedics)

Exclusion Criteria

• Active COVID-19 disease
• Prior COVID-19 disease
• Current fever, cough, shortness of breath
• Allergy to chloroquine or hydroxychloroquine
• Prior retinal eye disease
• Known Chronic Kidney disease, Stage 4 or 5 or dialysis
• Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency
• Weight <40 kg
• Prolonged QT syndrome
• Current use of hydroxychloroquine, chloroquine, or cardiac medicines of flecainide, amiodarone, digoxin, procainamide, or propafenone
• Current use of medications with known significant drug-drug interactions: artemether, lumefantrine, mefloquine, tamoxifen, or methotrexate.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Group	Placebo	Placebo 2 tabs once, followed by 2 tabs 6 to 8 hours later, thereafter two tabs weekly or twice weekly for the duration of follow up, up to 12 weeks
Intervention Twice Weekly	Hydroxychloroquine	400mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg twice weekly for the duration of follow up, up to 12 weeks
Intervention Once Weekly	Hydroxychloroquine	400 mg orally once, followed by 400mg 6 to 8 hours later, thereafter 400mg weekly for the duration of follow up, up to 12 weeks

Primary Outcome Measures

Name	Time	Method
COVID-19-free Survival	up to 12 weeks	Outcome reported as the number of participants in each arm who are COVID-19-free at the end of study treatment.

Secondary Outcome Measures

Name	Time	Method
Incidence of Possible COVID-19 Symptoms	up to 12 weeks	Outcome reported as the count of participants in each arm who report COVID-19-related symptoms during study treatment.
Incidence of All-cause Study Medicine Discontinuation	up to 12 weeks	Outcome reported as the count of participants in each arm who discontinue study medication use for any reason during treatment.
Ordinal Scale of COVID-19 Disease Maximum Severity if COVID-19 Diagnosed at Study End	up to 12 weeks	Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.
Number of Confirmed SARS-CoV-2 Detection	up to 12 weeks	Outcome reported as the number of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.
Incidence of Hospitalization for COVID-19 or Death	up to 12 weeks	Outcome reported as the number of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.
Incidence of Possible Study Medication-related Side Effects	up to 12 weeks	Outcome reported as the number of participants in each arm who experience possible medication-related side effects during study treatment.

Trial Locations

Locations (2)

Nationwide Enrollment via Internet, please email: covid19@umn.edu; 🇺🇸 Minneapolis, Minnesota, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States