Post-exposure Prophylaxis / Preemptive Therapy for SARS-Coronavirus-2 (COVID-19 PEP)

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ClinicalTrials.gov Identifier: NCT04308668

Recruitment Status : Completed

First Posted : March 16, 2020

Last Update Posted : July 17, 2020

Sponsor:

Collaborators:

McGill University Health Centre/Research Institute of the McGill University Health Centre

University of Manitoba

University of Alberta

Information provided by (Responsible Party):

University of Minnesota

Study Description

Brief Summary:

Study Objective:

To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus.
To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.

Condition or disease	Intervention/treatment	Phase
Corona Virus Infection Acute Respiratory Distress Syndrome SARS-CoV Infection Coronavirus Coronavirus Infections	Drug: Hydroxychloroquine Other: Placebo	Phase 3

Detailed Description:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing COVID19. The current strategy uses a public health model of identifying infected cases, isolation, and quarantine to stop transmission. Once exposed, observation is standard-of-care. Therapy is generally not given to persons who are not hospitalized. The doses of hydroxychloroquine being used are within the normal standard FDA-approved doses.

Hydroxychloroquine may have antiviral effects against SARS-COV2 which may prevent COVID-19 disease or early preemptive therapy may decrease disease severity. This trial will use a modification of standard malaria dosing of hydroxychloroquine to provide post-exposure prophylaxis to prevent disease or preemptive therapy for those with early symptoms. People around the the United States and Canada can participate to help answer this critically important question. No in-person visits are needed.

This trial is targeting 5 groups of people NATIONWIDE to participate:

If you are symptomatic with a positive COVID-19 test within the first 4 days of symptoms and are not hospitalized; OR
If you live with someone who has been diagnosed with COVID-19, with your last exposure within the last 4 days, and do not have any symptoms; OR
If you live with someone who has been diagnosed with COVID-19, and your symptoms started within the last 4 days; OR
If you have had occupational exposure with known exposure to someone with lab-confirmed COVID-19 within the last 4 days and do not have symptoms; OR
If you have had occupational exposure with known exposure to someone with lab-confirmed COVID-19 within the last 4 days AND have compatible symptoms starting within the last 4 days;

You may participate if you live anywhere in the United States (including territories) or in the Canadian Provinces of Quebec, Manitoba, Alberta, or Ontario.

For information on how to participate in the research trial, go to covidpep.umn.edu or email covid19@umn.edu for instructions. Please check your spam folder if you email.

In Canada, for trial information, please go to: www.covid-19research.ca

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	1309 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	Asymptomatic participants are randomized and analyzed separate from symptomatic participants.
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Post-exposure Prophylaxis or Preemptive Therapy for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial
Actual Study Start Date :	March 17, 2020
Actual Primary Completion Date :	May 20, 2020
Actual Study Completion Date :	May 20, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Coronavirus Infections

Drug Information available for: Hydroxychloroquine Hydroxychloroquine sulfate

Genetic and Rare Diseases Information Center resources: Respiratory Distress Syndrome, Infant Acute Respiratory Distress Syndrome Severe Acute Respiratory Syndrome

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment Participants in this arm will receive the study drug.	Drug: Hydroxychloroquine 200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days Other Name: Plaquenil
Placebo Comparator: Placebo Participants in this arm will receive a placebo treatment.	Other: Placebo 4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Outcome Measures

Primary Outcome Measures :

Incidence of COVID19 Disease among those who are asymptomatic at baseline [ Time Frame: 14 days ]
Number of participants at 14 days post enrollment with active COVID19 disease.
Overall change in disease severity over 14 days among those who are symptomatic at baseline [ Time Frame: 14 days ]
Repeated Measure mixed regression model of change in: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

Secondary Outcome Measures :

Incidence of Hospitalization [ Time Frame: 14 days ]
Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Incidence of Death [ Time Frame: 90 days ]
Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.
Incidence of Confirmed SARS-CoV-2 Detection [ Time Frame: 14 days ]
Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.
Incidence of Symptoms Compatible with COVID19 (possible disease) [ Time Frame: 90 days ]
Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID19 infection.
Incidence of All-Cause Study Medicine Discontinuation or Withdrawal [ Time Frame: 14 days ]
Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.
Overall symptom severity at 5 and 14 days [ Time Frame: 5 and 14 days ]
Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Ordinal Scale of COVID19 Disease Severity at 14 days among those who are symptomatic at trial entry [ Time Frame: 14 days ]
Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the percent of participants who fall into each category per arm.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

Provision of informed consent
Exposure to a COVID19 case within 4 days as either a household contact or occupational exposure, OR
Symptomatic COVID19 case with confirmed diagnosis within 4 days of symptom onset OR symptomatic high risk exposure with known COVID19 contact and within 4 days of symptom onset;

Exclusion Criteria:

Current hospitalization
Allergy to hydroxychloroquine
Retinal eye disease
Known glucose-6 phosphate dehydrogenase (G-6-PD) deficiency
Known chronic kidney disease, stage 4 or 5 or receiving dialysis
Structural or ischemic heart disease
Personal or Family History of Prolonged QT syndrome
Weight < 50 kg
Known Porphyria
Current use of: hydroxychloroquine or cardiac medicines of: flecainide, Tambocor; amiodarone, Cordarone, Pacerone; digoxin or Digox, Digitek, Lanoxin; procainamide or Procan, Procanbid, propafenone, Rythmal, sotalol;
Current use of medicines which prolong the QT interval including:
- Antimicrobials: levofloxacin, ciprofloxacin, moxifloxacin, azithromycin, clarithromycin, erythromycin, ketoconazole, itraconazole, or mefloquine
- Antidepressants: amitriptyline, citalopram, desipramine, escitalopram, imipramine, doxepin, fluoxetine, wellbutrin, or venlafaxine
- Antipsychotic or mood stabilizers: haloperidol, droperidol, lithium, quetiapine, thioridazine, ziprasidone
- Methadone
- Sumatriptan, zolmitriptan

Contacts and Locations

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): NCT04308668

Locations

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United States, Minnesota
Nationwide Enrollment via Internet, please email: covid19@umn.edu
Minneapolis, Minnesota, United States, 55455
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada
Canada, Manitoba
University of Manitoba
Winnipeg, Manitoba, Canada
Canada, Quebec
Research Institute of the McGill University Heath Centre
Montréal, Quebec, Canada

Sponsors and Collaborators

University of Minnesota

McGill University Health Centre/Research Institute of the McGill University Health Centre

University of Manitoba

University of Alberta

Investigators

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Principal Investigator:	David Boulware, MD, MPH	University of Minnesota

Study Documents (Full-Text)

Documents provided by University of Minnesota:

Study Protocol and Statistical Analysis Plan [PDF] April 24, 2020

Informed Consent Form [PDF] April 24, 2020

More Information

Publications of Results:

Boulware DR, Pullen MF, Bangdiwala AS, Pastick KA, Lofgren SM, Okafor EC, Skipper CP, Nascene AA, Nicol MR, Abassi M, Engen NW, Cheng MP, LaBar D, Lother SA, MacKenzie LJ, Drobot G, Marten N, Zarychanski R, Kelly LE, Schwartz IS, McDonald EG, Rajasingham R, Lee TC, Hullsiek KH. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med. 2020 Aug 6;383(6):517-525. doi: 10.1056/NEJMoa2016638. Epub 2020 Jun 3.

Other Publications:

Lother SA, Abassi M, Agostinis A, Bangdiwala AS, Cheng MP, Drobot G, Engen N, Hullsiek KH, Kelly LE, Lee TC, Lofgren SM, MacKenzie LJ, Marten N, McDonald EG, Okafor EC, Pastick KA, Pullen MF, Rajasingham R, Schwartz I, Skipper CP, Turgeon AF, Zarychanski R, Boulware DR. Post-exposure prophylaxis or pre-emptive therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): study protocol for a pragmatic randomized-controlled trial. Can J Anaesth. 2020 Sep;67(9):1201-1211. doi: 10.1007/s12630-020-01684-7. Epub 2020 May 7.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Akhtar S, Das JK, Ismail T, Wahid M, Saeed W, Bhutta ZA. Nutritional perspectives for the prevention and mitigation of COVID-19. Nutr Rev. 2021 Feb 11;79(3):289-300. doi: 10.1093/nutrit/nuaa063.

Skipper CP, Pastick KA, Engen NW, Bangdiwala AS, Abassi M, Lofgren SM, Williams DA, Okafor EC, Pullen MF, Nicol MR, Nascene AA, Hullsiek KH, Cheng MP, Luke D, Lother SA, MacKenzie LJ, Drobot G, Kelly LE, Schwartz IS, Zarychanski R, McDonald EG, Lee TC, Rajasingham R, Boulware DR. Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19 : A Randomized Trial. Ann Intern Med. 2020 Oct 20;173(8):623-631. doi: 10.7326/M20-4207. Epub 2020 Jul 16.

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Responsible Party:	University of Minnesota
ClinicalTrials.gov Identifier:	NCT04308668
Other Study ID Numbers:	MED-2020-28673
First Posted:	March 16, 2020 Key Record Dates
Last Update Posted:	July 17, 2020
Last Verified:	July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	De-identified dataset will be available within 1 month of publication.
Supporting Materials:	Study Protocol Statistical Analysis Plan (SAP)
Time Frame:	at time of publication
Access Criteria:	To be publicly provided
URL:	http://covidpep.umn.edu

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

Keywords provided by University of Minnesota:


COVID-19 Corona Virus SARS-COV-2 Coronavirus

Additional relevant MeSH terms:

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Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Coronaviridae Infections Nidovirales Infections RNA Virus Infections Virus Diseases Lung Diseases Respiratory Tract Diseases	Respiration Disorders Infant, Premature, Diseases Infant, Newborn, Diseases Lung Injury Respiratory Tract Infections Hydroxychloroquine Antimalarials Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antirheumatic Agents

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