Pre-exposure Prophylaxis for SARS-Coronavirus-2

• ClinicalTrials.gov Identifier: NCT04328467
• Recruitment Status: Completed
• First Posted: March 31, 2020
• Results First Posted: June 30, 2021
• Last Update Posted: July 2, 2021
• Sponsor: University of Minnesota
• Information provided by (Responsible Party): University of Minnesota

Tracking Information

• First Submitted Date: March 27, 2020
• First Posted Date: March 31, 2020
• Results First Submitted Date: June 25, 2021
• Results First Posted Date: June 30, 2021
• Last Update Posted Date: July 2, 2021
• Actual Study Start Date: April 6, 2020
• Actual Primary Completion Date: July 13, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 25, 2021)

COVID-19-free Survival [ Time Frame: 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.

Original Primary Outcome Measures (submitted: March 30, 2020)

COVID-19-free survival [ Time Frame: up to 12 weeks ]

Outcome reported as the percent of participants in each arm who are COVID-19-free at the end of study treatment.

Current Secondary Outcome Measures (submitted: June 30, 2021)

• Number of Confirmed SARS-CoV-2 Detection [ Time Frame: 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 Possible COVID-19 Symptoms [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
• Incidence of Hospitalization for COVID-19 or Death [ Time Frame: 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 [ Time Frame: up to 12 weeks ]
  Outcome reported as the number of participants in each arm who experience possible medication-related side effects during study treatment.

Original Secondary Outcome Measures (submitted: March 30, 2020)

• Incidence of confirmed SARS-CoV-2 detection [ Time Frame: up to 12 weeks ]
  Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.
• Incidence of possible COVID-19 symptoms [ Time Frame: up to 12 weeks ]
  Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment.
• Incidence of all-cause study medicine discontinuation [ Time Frame: up to 12 weeks ]
  Outcome reported as the percent 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 [ Time Frame: 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.
• Incidence of Hospitalization for COVID-19 or death [ Time Frame: up to 12 weeks ]
  Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.
• Incidence of study medication-related side effects [ Time Frame: up to 12 weeks ]
  Outcome reported as the percent of participants in each arm who experience medication-related side effects during study treatment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pre-exposure Prophylaxis for SARS-Coronavirus-2
• Official Title: Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• COVID-19
• Corona Virus Infection
• ARDS
• Acute Respiratory Distress Syndrome

Intervention

• Drug: Hydroxychloroquine
  Hydroxychloroquine; 200mg tablet; oral
  Other Name: Plaquenil
• Other: Placebo
  Placebo; tablet; oral

Study Arms

• Experimental: Intervention Once Weekly
  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
  Intervention: Drug: Hydroxychloroquine
• Experimental: Intervention Twice Weekly
  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: Drug: Hydroxychloroquine
• Placebo Comparator: Control Group
  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: Other: Placebo

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 25, 2021): 1483
• Original Estimated Enrollment (submitted: March 30, 2020): 3500
• Actual Study Completion Date: July 13, 2020
• Actual Primary Completion Date: July 13, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04328467
• Other Study ID Numbers: MED-2020-28720
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: University of Minnesota
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Minnesota
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Radha Rajasingham, MD; University of Minnesota

• PRS Account: University of Minnesota
• Verification Date: June 2021