COVID-19 PEP- High-risk Individuals in Long-term and Specialized Care - Canada

May 20, 2020 updated by: Lawson Health Research Institute

Safety and Efficacy of Post-exposure Prophylaxis With Hydroxychloroquine (HCQ) for the Prevention of COVID-19 in High-risk Older Individuals in Long-term and Specialized Care: A Double-blind Randomized Control Trial

Older adults are at the highest risk of complications and severe illness for 2019-nCoV infections. Hydroxychloroquine (HCQ), an emerging chemoprophylaxis, which holds clinical and mechanistic plausibility, will help to reduce disease incidence and mitigate disease severity across in-patient settings. This study is designed to assess the safety and efficacy of post-exposure prophylaxis with hydroxychloroquine (HCQ) for the prevention of Coronavirus Infectious Disease-19 (COVID-19) in high-risk older individuals in long-term and specialized care.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Rationale: HCQ blocks SARS-CoV-2 entry into host cells in vitro, and it also has immunomodulatory effects; therefore, it may be effective in reducing viral presence and inhibiting immunopathological mechanisms of COVID-19 in patients if administered before manifestation of clinical symptoms.

Hypothesis: the investigators hypothesize that prophylactic HCQ treatment in high-risk individuals Long Term Care (LTC) and Specialized Care (SC) settings post confirmed exposure to SARS-CoV-2 will reduce morbidity and mortality to COVID-19 via a) reduced viral presence during the acute phase of the infection, and b) inducing protective immune cell populations, c) reducing the production of inflammatory cytokines in peripheral blood.

Objectives:

Test if HCQ can prevent the development of COVID-19 in high-risk individuals in institutions which provide LTC or SC after known accidental exposure to the SARS-CoV-2.

Test if early presumptive therapy in asymptomatic high-risk individuals exposed to SARS-CoV-2 can limit disease progression and acute care hospitalization.

Study drug or placebo initiated after exposure, but before symptoms of elevated temperature, cough, or shortness of breath.

If the exposed patients developed respiratory symptoms, specifically fever, cough or dyspnea, the blinded treatment will be continued and usual supportive care added as per clinician preference. If antiviral or immunomodulatory therapy is recommended, the patient treatment allocation will be unblinded, and treatment may be administered as per clinician preference with consideration of locally available agents.

Safety will be closely monitored during the study conduct with safety labs and 6 lead ECGs at baseline, day 2, 5, 12, and 19

Study Type

Interventional

Enrollment (Anticipated)

336

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age over 40 with two or more high-risk comorbidities that have been found to confer a higher risk of mortality including but not limited to :

    chronic lung disease to include: Chronic obstructive lung disease, interstitial lung disease or diffuse parenchymal disease moderate to severe asthma

    • Cardiac conditions to include: recent myocardial infarction (within the last three months) or poorly controlled heart failure
    • severe obesity (body mass index [BMI] of 40 or higher)
    • Diabetes (type 1 or 2)
    • chronic kidney disease undergoing dialysis
    • liver cirrhosis

    OR Age over 60.

  2. Patient/resident in an Institute (to include a rehabilitation, long term care facility, mental health facility or veteran's care) that provides bed-based care in shared semi-private or ward rooms (i.e. two or more to a room) with a patient with confirmed COVID-19 for at least 6 hours in the absence of contact and droplet precautions.
  3. Exposure with a documented or suspected COVID-19 case or from a symptomatic ( defined as common symptoms of COVID-19 including but not limited to fever, lethargy, dry cough, shortness of breath) health care worker providing direct patient contact within 3 feet without a mask for > 15min or any physical contact with the staff. Exposure may occur in single or shared bedrooms. Exposure may occur in a common dining or activity or sitting area. Any patient sharing a room or within 3 feet for > 15min or any physical contact without a mask will be considered as a contact. Patients or staff are considered as infectious for 48hrs before any symptoms onset and until masked or cleared by 2 negative swabs.
  4. No prior treatment with acetaminophen or NSAIDs or willing to stop present prescription of regular or PRN acetaminophen.
  5. Informed consent (in person or by telephone/e-mail with SDM)

Exclusion Criteria:

  1. Greater than 96 hours since last exposure
  2. Presence of fever (T>37.8), new onset cough, or shortness of breath at enrollment
  3. A baseline O2 saturation less than 90% (as measured by pulse oximetry) on room air
  4. Screening ECG QTc interval greater than 500ms by either a 12 lead or 6 lead ECG.
  5. Concomitant drug-drug interactions (Artemether, Dapsone, Lumefantrine or Mefloquine amiodarone, digoxin, dofetilide, flecainide, procainamide, sotalol, or propafenone levofloxacin, ciprofloxacin, moxifloxacin, azithromycin, clarithromycin, erythromycin, ketoconazole, or itraconazole methadone sumatriptan, or zolmitriptan systemic chemotherapy.)
  6. Already on active palliative care measures (Palliative performance score (PPS) less than 30%)
  7. Hypersensitivity reaction to chloroquine, hydroxychloroquine or aminoquinolines
  8. History of retinal disease due to previous use of 4-aminoquinoline
  9. Prior documented and known at enrollment, retinal eye disease or maculopathy including but not limited to diabetic retinopathy, retinal detachment, retinitis pigmentosa or macular degeneration
  10. Known glucose-6 phosphate dehydrogenase (G6PD) deficiency
  11. Known Porphyria
  12. Acute delirium
  13. Inability to swallow oral study drug/placebo (even after crushed in the same manner as regular prescribed medications)
  14. Diagnosis of immunodeficiency (e.g. HIV, transplantation) or receiving systemic steroid therapy (>10mg prednisone daily or equivalent) or any other form of immunosuppressive therapy prior to trial treatment
  15. Women who are pregnant or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Hydroxychloroquine 200mg
Regular Dose 400mg orally once, followed in 8 hours by 400mg, then 200mg twice a day for 4 consecutive days (5 days in total) Modified Dose 400mg orally once, followed in 8 hours by 400mg, then 200mg once a day for 4 consecutive days (5 days in total) Modified doses are for individuals with body weight below 40 kg, renal impairment with a creatinine clearance less than 10mls/min or QTc interval greater than 480 but less than 500.
Drug: Hydroxychloroquine
Hydroxychloroquine vs placebo (1:1 design) double blind intervention
PLACEBO_COMPARATOR: Placebo Arm
The placebo arm will be matched to study drug to maintain the study blind. Regular Dose Placebo 2 tabs once, followed in 8 hours by 2 tabs, then 1 tab twice a day for 4 consecutive days (5 days in total) Modified Dose Placebo 2 tabs once, followed in 8 hours by 2 tabs, then 1 tab once a day for 4 consecutive days (5 days in total) Modified doses are for individuals with body weight below 40 kg, renal impairment with a creatinine clearance less than 10mls/min or QTc interval greater than 480 but less than 500.
Drug: Placebo
Hydroxychloroquine vs placebo (1:1 design) double blind intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of symptomatic fever >37.8, dry cough, or shortness of breath (resident/patient report or nurse observation) respiratory infection with confirmed PCR+ result for SARS-CoV-2.
Time Frame: baseline through day 90
baseline through day 90

Secondary Outcome Measures

Outcome Measure
Time Frame
Requirement for admission to acute care hospital and/or ICU admission or death
Time Frame: baseline through day 90
baseline through day 90
Asymptomatic PCR+ SARS-CoV-2 test result
Time Frame: baseline, days 2, 5, 12, and 19
baseline, days 2, 5, 12, and 19
Time to clinical recovery (TTCR).
Time Frame: baseline through day 90
baseline through day 90

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lawson Health Research Institute

Investigators

  • Principal Investigator: Michael J Borrie, MB ChB, Lawson Health Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

May 19, 2020

Primary Completion (ANTICIPATED)

April 30, 2021

Study Completion (ANTICIPATED)

April 30, 2021

Study Registration Dates

First Submitted

May 13, 2020

First Submitted That Met QC Criteria

May 20, 2020

First Posted (ACTUAL)

May 21, 2020

Study Record Updates

Last Update Posted (ACTUAL)

May 21, 2020

Last Update Submitted That Met QC Criteria

May 20, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9881 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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