Pre-exposure Prophylaxis for SARS-Coronavirus-2

University of Minnesota (UMN)

Status and phase: Completed; Phase 3

Conditions: COVID-19; Corona Virus Infection; Acute Respiratory Distress Syndrome; ARDS

Treatments: Drug: Hydroxychloroquine; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04328467

MED-2020-28720

Details and patient eligibility

About

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

Full 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.

Enrollment: 1,483 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,483 participants in 3 patient groups, including a placebo group

Intervention Once Weekly

Experimental group

Description:

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

Treatment:

Drug: Hydroxychloroquine

Intervention Twice Weekly

Experimental group

Description:

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

Treatment:

Drug: Hydroxychloroquine

Control Group

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo