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

NCT04308668 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: MED-2020-28673
• Study Type: interventional
• Target: 1,312
• Locations: 2 countries
• Sites: 5

Brief Summary

Study Objective:

1. 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. 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.

Conditions

Corona Virus Infection; Acute Respiratory Distress Syndrome; SARS-CoV Infection; Coronavirus; Coronavirus Infections

Keywords

COVID-19; Corona Virus; SARS-COV-2; Coronavirus

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (7)

• Rate of Hospitalization

  14 days

• Rate of Death

  Approximately 30 days

• Rate of Confirmed SARS-CoV-2 Detection

  14 days

• Occurrence of Symptoms Compatible With COVID-19 (Possible Disease)

  14 days

• Rate of All-Cause Study Medicine Discontinuation or Withdrawal

  14 days

Study Arms (2)

Treatment

EXPERIMENTAL

Participants in this arm will receive the study drug.

Drug: Hydroxychloroquine

Placebo

PLACEBO COMPARATOR

Participants in this arm will receive a placebo treatment.

Other: Placebo

Interventions

Hydroxychloroquine DRUG

200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days

Also known as: Plaquenil

Treatment

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Minnesota: lead
• McGill University Health Centre/Research Institute of the McGill University Health Centre: collaborator
• University of Manitoba: collaborator
• University of Alberta: collaborator

Study Sites (5)

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

Minneapolis, Minnesota, 55455, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Alberta

Edmonton, Alberta, Canada

Location

University of Manitoba

Winnipeg, Manitoba, Canada

Location

Research Institute of the McGill University Heath Centre

Montreal, Quebec, Canada

Location

Related Publications (12)

• 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.

  PMID: 32383125 BACKGROUND

• 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, Mitja 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.

  PMID: 32363212 BACKGROUND

• 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.

  PMID: 32344449 BACKGROUND

• 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. No abstract available.

  PMID: 32345336 BACKGROUND

• 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.

  PMID: 33553471 BACKGROUND

• 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. No abstract available.

  PMID: 32668109 BACKGROUND

• 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.

  PMID: 32492293 RESULT

• 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.

  PMID: 32673060 RESULT

• 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, McDonald EG, Lee TC, Hullsiek KH, Boulware DR, Rajasingham R. Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19. Open Forum Infect Dis. 2020 Oct 19;7(11):ofaa500. doi: 10.1093/ofid/ofaa500. eCollection 2020 Nov.

  PMID: 33204764 RESULT

• 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. No abstract available.

  PMID: 33721539 RESULT

• Nicol MR, Boulware DR, Rajasingham R. Reply to Neves. Clin Infect Dis. 2021 Oct 5;73(7):e1772-e1774. doi: 10.1093/cid/ciaa1809. No abstract available.

  PMID: 33274360 RESULT

• 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.

  PMID: 33570583 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; Respiratory Distress Syndrome; Severe Acute Respiratory Syndrome; COVID-19

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: David Boulware, MD, MPH
• Organization: University of Minnesota

covid19@umn.edu

6125552020

Study Officials

• David Boulware, MD, MPH

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Asymptomatic participants are randomized and analyzed separate from symptomatic participants.

Study Record Dates

• First Submitted: March 11, 2020
• First Posted: March 16, 2020
• Study Start: March 17, 2020
• Primary Completion: May 20, 2020
• Study Completion: May 20, 2020
• Last Updated: May 13, 2021
• Results First Posted: May 13, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: at time of publication
• Access Criteria: To be publicly provided. Please register at the website to receive the dataset.

Locations

US (2); CA (3)