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

• ClinicalTrials.gov Identifier: NCT04308668
• Recruitment Status: Recruiting
• First Posted: March 16, 2020
• Last Update Posted: April 3, 2020
• Sponsor: University of Minnesota
• 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:

1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus.
2. To test if preemptive therapy with hydroxychloroquine early in the sypmptomatic COVID-19 disease course can prevent progression of persons with known symptomatic COVID19 disease, decrease hospitalization.

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.

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:

1. If you are symptomatic with a positive COVID-19 test within the first 4 days of symptoms and are not hospitalized; OR
2. 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
3. If you live with someone who has been diagnosed with COVID-19, and your symptoms started within the last 4 days; OR
4. If you are a healthcare worker or first responder with known exposure to someone with lab-confirmed COVID-19 within the last 4 days and do not have symptoms; OR
5. If you are a healthcare worker or first responder 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, or Alberta.

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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 3000 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 and Preemptive Therapy for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial
• Actual Study Start Date: March 17, 2020
• Estimated Primary Completion Date: April 21, 2020
• Estimated Study Completion Date: May 12, 2020

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 :

1. Incidence of COVID19 Disease among those who are asymptomatic at trial entry [ Time Frame: 14 days ]
   Number of participants at 14 days post enrollment with active COVID19 disease.
2. 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.

Secondary Outcome Measures :

1. Incidence of Hospitalization [ Time Frame: 14 days ]
   Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
2. 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.
3. 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.
4. 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.
5. 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.
6. Overall symptom severity at 5 and 14 day [ Time Frame: 5 and 14 days ]
   Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

Eligibility Criteria

• 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 healthcare worker or household contact, OR
• Symptomatic COVID19 case with confirmed diagnosis within 4 days of symptom onset OR symptomatic healthcare worker 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
• Weight < 40 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)

Contacts and Locations

Contacts

Contact: David Boulware (Please email), MD, MPH; 6126249996; covid19@umn.edu

Locations

United States, Minnesota

Nationwide Enrollment via Internet, please email: covid19@umn.edu; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: David Boulware covid19@umn.edu

University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: David R Boulware, MD, MPH covid19@umn.edu

Sub-Investigator: Matt Pullen, MD

Sub-Investigator: Sarah Lofgren, MD

Sub-Investigator: Caleb Skipper, MD

Sub-Investigator: Radha Rajasingham, MD

Sub-Investigator: Mahsa Abassi, DO, MPH

Sub-Investigator: Ananta Bangdiwala, MS

Sub-Investigator: Kathy Hullsiek, PhD

Sub-Investigator: Katelyn Pastick

Sub-Investigator: Elizabeth Okafor

United States, New York

Internet; Recruiting

New York, New York, United States, 10001

Contact: David Boulware, MD covid19@umn.edu

Canada, Alberta

University of Alberta; Recruiting

Edmonton, Alberta, Canada

Contact: Ilan Schwartz, MD alberta@idtrials.com

Canada, Manitoba

University of Manitoba; Recruiting

Winnipeg, Manitoba, Canada

Contact: Ryan Zarychanski, MD manitoba@idtrials.com

Contact: Lauren E Kelly, PhD manitoba@idtrials.com

Sub-Investigator: Glen Drobot, MD

Sub-Investigator: Lauren MacKenzie, MD

Sub-Investigator: Sylvain Lother, MD

Canada, Quebec

Research Institute of the McGill University Heath Centre; Recruiting

Montréal, Quebec, Canada

Contact: Todd C Lee, MD 5149341934 ext 32965 quebec@idtrials.com

Sub-Investigator: Emily G McDonald, MDCM MSc

Sub-Investigator: Matthew P Chang, MDCM

Sub-Investigator: Alek Lefebvre

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

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

More Information

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT04308668
• Other Study ID Numbers: STUDY00009267
• First Posted: March 16, 2020
• Last Update Posted: April 3, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

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