Clinical trial NCT04328467: Pre-exposure Prophylaxis for SARS-Coronavirus-2
Official title: Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Corona Virus Infection
ARDS
Acute Respiratory Distress Syndrome
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2020-03-31
Enrollment: 1483
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: COVID-19-free Survival
timeFrame: up to 12 weeks
Secondary outcomes:
measure: Number of Confirmed SARS-CoV-2 Detection
timeFrame: up to 12 weeks
measure: Incidence of Possible COVID-19 Symptoms
timeFrame: up to 12 weeks
measure: Incidence of All-cause Study Medicine Discontinuation
timeFrame: up to 12 weeks
measure: Ordinal Scale of COVID-19 Disease Maximum Severity if COVID-19 Diagnosed at Study End
timeFrame: up to 12 weeks
measure: Incidence of Hospitalization for COVID-19 or Death
timeFrame: up to 12 weeks
measure: Incidence of Possible Study Medication-related Side Effects
timeFrame: up to 12 weeks
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Nationwide Enrollment via Internet, please email: covid19@umn.edu
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Radha Rajasingham, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rajasingham R, Bangdiwala AS, Nicol MR, Skipper CP, Pastick KA, Axelrod ML, Pullen MF, Nascene AA, Williams DA, Engen NW, Okafor EC, Rini BI, Mayer IA, McDonald EG, Lee TC, Li P, MacKenzie LJ, Balko JM, Dunlop SJ, Hullsiek KH, Boulware DR, Lofgren SM; COVID PREP team. Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial. Clin Infect Dis. 2021 Jun 1;72(11):e835-e843. doi: 10.1093/cid/ciaa1571.
citation: Lofgren SM, Nicol MR, Bangdiwala AS, Pastick KA, Okafor EC, Skipper CP, Pullen MF, Engen NW, Abassi M, Williams DA, Nascene AA, Axelrod ML, Lother SA, MacKenzie LJ, Drobot G, Marten N, Cheng MP, Zarychanski R, Schwartz IS, Silverman M, Chagla Z, Kelly LE, McDonald EG, Lee TC, Hullsiek KH, Boulware DR, Rajasingham R. Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19. Open Forum Infect Dis. 2020 Oct 19;7(11):ofaa500. doi: 10.1093/ofid/ofaa500. eCollection 2020 Nov.