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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04397328
Recruitment Status : Not yet recruiting
First Posted : May 21, 2020
Last Update Posted : May 21, 2020
Sponsor:
Information provided by (Responsible Party):
Lawson Health Research Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Hydroxychloroquine Drug: Placebo Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 336 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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
Estimated Study Start Date : May 19, 2020
Estimated Primary Completion Date : April 30, 2021
Estimated Study Completion Date : April 30, 2021

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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 ]

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


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04397328


Contacts
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Contact: Michael J Borrie, MB ChB 519-685-4292 ext 46600 memory@sjhc.london.on.ca

Sponsors and Collaborators
Lawson Health Research Institute
Investigators
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Principal Investigator: Michael J Borrie, MB ChB Lawson Health Research Institute
Publications:

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Responsible Party: Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT04397328    
Other Study ID Numbers: 9881
First Posted: May 21, 2020    Key Record Dates
Last Update Posted: May 21, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Lawson Health Research Institute:
COVID-19
Hydroxychloroquine
Double Blind Randomized Control Trial
Prophylaxis
High risk
Long term / specialized care
Additional relevant MeSH terms:
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Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents