Post-exposure Prophylaxis / Preemptive Therapy for SARS-Coronavirus-2

Acute Respiratory Distress Syndrome Clinical Trial

— COVID-19 PEP  

Official title:

Post-exposure Prophylaxis or Preemptive Therapy for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04308668
• Other study ID #: MED-2020-28673
• Status: Completed
• Phase: Phase 3
• Start date: March 17, 2020
• Est. completion date: May 20, 2020

Study information

• Verified date: May 2021
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.

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: 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 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 5. 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1312
• Est. completion date: May 20, 2020
• Est. primary completion date: May 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Communicable Diseases
• Corona Virus Infection
• Coronavirus
• Coronavirus Infections
• Infection
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

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:
• Placebo
4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days

Locations

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

Sponsors (4)

Lead Sponsor	Collaborator
University of Minnesota	McGill University Health Centre/Research Institute of the McGill University Health Centre, University of Alberta, University of Manitoba

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (11)

Al-Kofahi M, Jacobson P, Boulware DR, Matas A, Kandaswamy R, Jaber MM, Rajasingham R, Young JH, Nicol MR. Finding the Dose for Hydroxychloroquine Prophylaxis for COVID-19: The Desperate Search for Effectiveness. Clin Pharmacol Ther. 2020 Oct;108(4):766-769. doi: 10.1002/cpt.1874. Epub 2020 Jun 1. — View Citation

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 — View Citation

Ingraham NE, Boulware D, Sparks MA, Schacker T, Benson B, Sparks JA, Murray T, Connett J, Chipman JG, Charles A, Tignanelli CJ. Shining a light on the evidence for hydroxychloroquine in SARS-CoV-2. Crit Care. 2020 Apr 28;24(1):182. doi: 10.1186/s13054-020-02894-7. — View Citation

Lofgren SM, Nicol MR, Bangdiwala AS, Pastick KA, Okafor EC, Skipper CP, Pullen MF, Engen NW, Abassi M, Williams DA, Nascene AA, Axelrod ML, Lother SA, MacKenzie LJ, Drobot G, Marten N, Cheng MP, Zarychanski R, Schwartz IS, Silverman M, Chagla Z, Kelly LE, — View Citation

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. — View Citation

Nicol MR, Boulware DR, Rajasingham R. Reply to author. Clin Infect Dis. 2020 Dec 4. pii: ciaa1809. doi: 10.1093/cid/ciaa1809. [Epub ahead of print] — View Citation

Okafor EC, Pastick KA, Rajasingham R. Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. Reply. N Engl J Med. 2020 Sep 10;383(11):1089. doi: 10.1056/NEJMc2023617. Epub 2020 Jul 15. — View Citation

Pastick KA, Okafor EC, Wang F, Lofgren SM, Skipper CP, Nicol MR, Pullen MF, Rajasingham R, McDonald EG, Lee TC, Schwartz IS, Kelly LE, Lother SA, Mitjà O, Letang E, Abassi M, Boulware DR. Review: Hydroxychloroquine and Chloroquine for Treatment of SARS-CoV-2 (COVID-19). Open Forum Infect Dis. 2020 Apr 15;7(4):ofaa130. doi: 10.1093/ofid/ofaa130. eCollection 2020 Apr. Review. — View Citation

Pullen MF, Pastick KA, Williams DA, Nascene AA, Bangdiwala AS, Okafor EC, Hullsiek KH, Skipper CP, Lofgren SM, Engen N, Abassi M, McDonald EG, Lee TC, Rajasingham R, Boulware DR. Lessons Learned From Conducting Internet-Based Randomized Clinical Trials During a Global Pandemic. Open Forum Infect Dis. 2020 Dec 28;8(2):ofaa602. doi: 10.1093/ofid/ofaa602. eCollection 2021 Feb. Review. — View Citation

Skipper CP, Boulware DR. Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19. Ann Intern Med. 2021 Mar;174(3):434-435. doi: 10.7326/L20-1426. — View Citation

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, Ra — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Active COVID-19 Disease at Day 14 Among Those Who Were Asymptomatic at Baseline	Number of participants at 14 days post enrollment with active COVID19 disease among those who were asymptomatic at baseline.	14 days
Primary	Change in Disease Severity Over 14 Days Among Those Who Are Symptomatic at Baseline	Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)	baseline and 14 days
Secondary	Rate of Hospitalization	Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.	14 days
Secondary	Rate of Death	Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease through study completion of 14 days. For those hospitalized within the 14-day study period, the protocol specified follow up would occur for up to 90 days to capture the final outcome of participants' hospitalization. Approximately 30-days was the maximal follow up for hospitalization outcome needed in the trial.	Approximately 30 days
Secondary	Rate of Confirmed SARS-CoV-2 Detection	Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.	14 days
Secondary	Occurrence of Symptoms Compatible With COVID-19 (Possible Disease)	Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID-19 infection.	14 days
Secondary	Rate of All-Cause Study Medicine Discontinuation or Withdrawal	Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.	14 days
Secondary	Overall Symptom Severity at 5 and 14 Days	Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)	5 and 14 days
Secondary	Number of Participants With Severe COVID-19 Disease at 14 Days Among Those Who Are Symptomatic at Trial Entry	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 number of participants who report a score of 3.	14 days