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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04397328
• Other study ID #: 9881
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 19, 2020
• Est. completion date: April 30, 2021

Study information

• Verified date: May 2020
• Source: Lawson Health Research Institute
• Contact: Michael J Borrie, MB ChB
• Phone: 519-685-4292
• Email: memory[@]sjhc.london.on.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 336
• Est. completion date: April 30, 2021
• Est. primary completion date: April 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Hydroxychloroquine
Hydroxychloroquine vs placebo (1:1 design) double blind intervention
• Placebo
Hydroxychloroquine vs placebo (1:1 design) double blind intervention

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Lawson Health Research Institute

References & Publications (13)

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Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, Ma K, Xu D, Yu H, Wang H, Wang T, Guo W, Chen J, Ding C, Zhang X, Huang J, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 26;368:m1091. doi: 10.1136/bmj.m1091. Erratum in: BMJ. 2020 Mar 31;368:m1295. — View Citation

Filatov A, Sharma P, Hindi F, Espinosa PS. Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy. Cureus. 2020 Mar 21;12(3):e7352. doi: 10.7759/cureus.7352. — View Citation

Ghasemnejad-Berenji H, Ghaffari Novin M, Hajshafiha M, Nazarian H, Hashemi SM, Ilkhanizadeh B, Ghasemnejad T, Sadeghpour S, Ghasemnejad-Berenji M. Immunomodulatory effects of hydroxychloroquine on Th1/Th2 balance in women with repeated implantation failure. Biomed Pharmacother. 2018 Nov;107:1277-1285. doi: 10.1016/j.biopha.2018.08.027. Epub 2018 Aug 29. — View Citation

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28. — View Citation

Juurlink DN. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. CMAJ. 2020 Apr 8. pii: cmaj.200528. doi: 10.1503/cmaj.200528. [Epub ahead of print] — View Citation

Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Li Y, Hu B. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Apr 10. doi: 10.1001/jamaneurol.2020.1127. [Epub ahead of print] — View Citation

McMichael TM, Currie DW, Clark S, Pogosjans S, Kay M, Schwartz NG, Lewis J, Baer A, Kawakami V, Lukoff MD, Ferro J, Brostrom-Smith C, Rea TD, Sayre MR, Riedo FX, Russell D, Hiatt B, Montgomery P, Rao AK, Chow EJ, Tobolowsky F, Hughes MJ, Bardossy AC, Oakley LP, Jacobs JR, Stone ND, Reddy SC, Jernigan JA, Honein MA, Clark TA, Duchin JS. Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington. N Engl J Med. 2020 Mar 27. doi: 10.1056/NEJMoa2005412. [Epub ahead of print] — View Citation

Mercuro NJ, Yen CF, Shim DJ, Maher TR, McCoy CM, Zimetbaum PJ, Gold HS. Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020 May 1. doi: 10.1001/jamacardio.2020.1834. [Epub ahead of print] — View Citation

Troyer EA, Kohn JN, Hong S. Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun. 2020 Apr 13. pii: S0889-1591(20)30489-X. doi: 10.1016/j.bbi.2020.04.027. [Epub ahead of print] Review. — View Citation

Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, Cuomo-Dannenburg G, Thompson H, Walker PGT, Fu H, Dighe A, Griffin JT, Baguelin M, Bhatia S, Boonyasiri A, Cori A, Cucunubá Z, FitzJohn R, Gaythorpe K, Green W, Hamlet A, Hinsley W, Laydon D, Nedjati-Gilani G, Riley S, van Elsland S, Volz E, Wang H, Wang Y, Xi X, Donnelly CA, Ghani AC, Ferguson NM. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020 Mar 30. pii: S1473-3099(20)30243-7. doi: 10.1016/S1473-3099(20)30243-7. [Epub ahead of print] Erratum in: Lancet Infect Dis. 2020 Apr 15;:. Lancet Infect Dis. 2020 May 4;:. — View Citation

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* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		baseline through day 90
Secondary	Requirement for admission to acute care hospital and/or ICU admission or death		baseline through day 90
Secondary	Asymptomatic PCR+ SARS-CoV-2 test result		baseline, days 2, 5, 12, and 19
Secondary	Time to clinical recovery (TTCR).		baseline through day 90