Corona Virus InfectionPhase 3NCT04421664
Preemptive Therapy for SARS-Coronavirus-2 (COVID-19 PEP Canada)
A Phase 3 study testing Hydroxychloroquine in people with Corona Virus Infection and SARS-CoV Infection, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 8 sites in 2 countries.
Trial summary
Study Objective: To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corona Virus Infection, SARS-CoV Infection, Coronavirus
- What is being tested?
- Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 25 Mar 2020to 17 Aug 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years of age or older AND provision of informed consent
- WITH
- Symptomatic COVID-19 disease with confirmed diagnosis with PCR+ SARS-CoV-2 within <= 4 days of symptoms
- OR
- Healthcare worker with compatible symptoms with exposure to known PCR+ case <= 14 days (and no available/pending testing for the individual).
Who cannot join
- Current hospitalization
- Allergy to chloroquine or hydroxychloroquine
- Severe diarrhea and/or vomiting
- Significant hepatic impairment defined as known cirrhosis with history of hepatic encephalopathy or ascites.
- Prior retinal eye disease
- Concurrent malignancy requiring chemotherapy
Show all 21Show fewer
- Known Chronic Kidney disease, Stage 4 or 5 or dialysis.
- Known glucose-6 phosphate dehydrogenase (G6PD) deficiency.
- Known ventricular arrythmia, known prolonged QTc interval, or any known episode of sudden cardiac death
- Known Porphyria
- Weight <40 kg
- Known Pregnancy of Breastfeeding
- Current use of chloroquine or hydroxychloroquine
- Current use of Artemether, Dapsone, Lumefantrine or Mefloquine
- Current use of Cardiac medicines: amiodarone, digoxin, dofetilide, flecainide, procainamide, sotalol, or propafenone
- Current use of the following antimicrobials: levofloxacin, ciprofloxacin, moxifloxacin, azithromycin, clarithromycin, erythromycin, ketoconazole, or itraconazole
- Current use of the following antidepressants: amitriptyline, citalopram, desipramine, escitalopram, imipramine, doxepin, fluoxetine, sertraline, bupropion (Wellbutrin), or venlafaxine
- Current use of the following antipsychotic or mood stabilizers: haloperidol, droperidol, lithium, quetiapine, thioridazine, ziprasidone
- Current use of methadone
- Current use of Sumatriptan, Zolmitriptan other than "as needed"
- Current use of systemic chemotherapy
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Canada7 sites
University of Alberta
Edmonton, Alberta
McMaster University
Hamilton, Ontario
Lawson Health Research Institute
London, Ontario
Research Institute of the McGill University Health Centre
Montreal, Quebec, H4A3J1
Eastern Health
St. John's, Newfoundland and Labrador
University of British Columbia
Vancouver, British Columbia
University of Manitoba
Winnipeg, Manitoba
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Study Objective:
To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.
Read the detailed description
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing COVID19. Therapy is generally not given to persons who are not hospitalized.
Hydroxychloroquine may have antiviral effects against SARS-CoV2 which may decrease disease severity when given early. This trial will use a modification of standard malaria dosing of hydroxychloroquine to provide preemptive therapy for those with early symptoms.
This study is a continuation of NCT04308668 which looked at post-exposure prophylaxis (now closed) and early treatment in the USA (now closed, data to be pooled) and Canada (which continues in this study). On April 28, 2020 NCT04308668 changed its primary outcome to symptomatic improvement in the preemptive therapy arm. This study continues enrollment for the primary ordinal outcome of hospitalization; hospitalization with intensive care stay; or death.
People in the participating Canadian provinces can help answer this critically important question. No in-person visits are needed.
The doses of hydroxychloroquine being used have been approved by Health Canada.
This trial is targeting the following groups of people:
If you are symptomatic with a positive COVID-19 test within the first 4 days of symptoms and are not hospitalized; OR If you have had occupational exposure with known exposure to someone with lab-confirmed COVID-19 within the last 14 days AND have compatible symptoms starting within the last 4 days;
You may participate if you live anywhere in the Canadian Provinces of Quebec, Manitoba, Alberta, British Columbia, Newfoundland or Ontario.
For information on how to participate in the research trial, go to:
www.covid-19research.ca
- Conditions
- Corona Virus Infection, SARS-CoV Infection, Coronavirus
- Being tested
- Hydroxychloroquine, Placebo oral tablet
- Keywords
- COVID-19, SARS-COV-2, Coronavirus, Corona virus
- Medical subject headings
- Coronavirus Infections, Severe Acute Respiratory Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days
Placebo oral tabletDrug
4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Participants in this arm will receive the study drug, hydroxychloroquine. Receives: Drug: Hydroxychloroquine |
| Placebo | Placebo comparator | Participants in this arm will receive a placebo treatment. Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ordinal Scale of COVID19 Disease Severity at 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.
Measured: 14 days
Secondary outcomes (6)
Incidence of Hospitalization
Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Measured: 14 days
Incidence of COVID-19 related Death
Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.
Measured: 90 days
Incidence of all-cause Death
Outcome reported as the number of participants in each arm who expire due to all causes.
Measured: 90 days
Incidence 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.
Measured: 14 days
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)
Measured: 5 and 14 days
Overall change in disease severity over 14 days among those who are symptomatic at baseline
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)
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2020
- Study start25 Mar 2020
- Primary completion17 Aug 2020
- Study completion17 Aug 2020
Why it stopped: Request of Health Canada after publication of https://doi.org/10.7326/M20-4207
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Corona Virus InfectionStudies of the same condition, open and under way.
- More trials run by McGill University Health Centre/Research Institute of the McGill University Health CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Sponsor type
- University, hospital or other
- Collaborators
- University of Manitoba, University of Alberta, University of British Columbia, McMaster University, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's, Eastern Health, University of Minnesota
- Responsible party
- Principal investigator, Todd C. Lee MD MPH FIDSA, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Todd C Lee, MD MPH FIDSA, Principal investigator, Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04421664
- Sponsor's protocol ID
- 2020-6549
- Status last verified
- Apr 2022
- First submitted
- 5 Jun 2020
- Last updated
- 15 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified dataset will be included with publication.
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.
PubMed 32383125Skipper 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.
PubMed 32673060Boulware 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.
PubMed 32492293
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preemptive Therapy for SARS-Coronavirus-2 (COVID-19 PEP Canada)
- ClinicalTrials.gov ID
- NCT04421664
- Acronym / sponsor ID
- 2020-6549
- Conditions
- Corona Virus Infection, SARS-CoV Infection, Coronavirus
- Keywords
- COVID-19, SARS-COV-2, Coronavirus, Corona virus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Request of Health Canada after publication of https://doi.org/10.7326/M20-4207
- Enrolment
- 70 participants (actual)
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health CentreUniversity, hospital or other
- Collaborators
- University of Manitoba, University of Alberta, University of British Columbia, McMaster University, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's, Eastern Health, University of Minnesota
- Study start
- 25 Mar 2020 (actual)
- Primary completion
- 17 Aug 2020 (actual)
- Study completion
- 17 Aug 2020 (actual)
- First posted
- 9 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study Objective:
To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.
Detailed description
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing COVID19. Therapy is generally not given to persons who are not hospitalized.
Hydroxychloroquine may have antiviral effects against SARS-CoV2 which may decrease disease severity when given early. This trial will use a modification of standard malaria dosing of hydroxychloroquine to provide preemptive therapy for those with early symptoms.
This study is a continuation of NCT04308668 which looked at post-exposure prophylaxis (now closed) and early treatment in the USA (now closed, data to be pooled) and Canada (which continues in this study). On April 28, 2020 NCT04308668 changed its primary outcome to symptomatic improvement in the preemptive therapy arm. This study continues enrollment for the primary ordinal outcome of hospitalization; hospitalization with intensive care stay; or death.
People in the participating Canadian provinces can help answer this critically important question. No in-person visits are needed.
The doses of hydroxychloroquine being used have been approved by Health Canada.
This trial is targeting the following groups of people:
If you are symptomatic with a positive COVID-19 test within the first 4 days of symptoms and are not hospitalized; OR If you have had occupational exposure with known exposure to someone with lab-confirmed COVID-19 within the last 14 days AND have compatible symptoms starting within the last 4 days;
You may participate if you live anywhere in the Canadian Provinces of Quebec, Manitoba, Alberta, British Columbia, Newfoundland or Ontario.
For information on how to participate in the research trial, go to:
www.covid-19research.ca
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: HydroxychloroquineParticipants in this arm will receive the study drug, hydroxychloroquine. |
| Placebo | Placebo comparator | Drug: Placebo oral tabletParticipants in this arm will receive a placebo treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 years of age or older AND provision of informed consent
- WITH
- Symptomatic COVID-19 disease with confirmed diagnosis with PCR+ SARS-CoV-2 within <= 4 days of symptoms
- OR
- Healthcare worker with compatible symptoms with exposure to known PCR+ case <= 14 days (and no available/pending testing for the individual).
Key exclusion criteria (21 listed)
- Current hospitalization
- Allergy to chloroquine or hydroxychloroquine
- Severe diarrhea and/or vomiting
- Significant hepatic impairment defined as known cirrhosis with history of hepatic encephalopathy or ascites.
- Prior retinal eye disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxychloroquine200mg tablet; 800 mg orally once, followed in 6 to 8 hours by 600 mg, then 600mg once a day for 4 consecutive days | Drug | Treatment |
| Placebo oral tablet4 placebo tablets once, followed in 6 to 8 hours by 3 tablets, then 3 tablets once-a-day for 4 consecutive days | Drug | Placebo |
Primary outcome
Ordinal Scale of COVID19 Disease Severity at 14 days
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.
6 secondary outcomes
Incidence of Hospitalization
Time frame: 14 days
Incidence of COVID-19 related Death
Time frame: 90 days
Incidence of all-cause Death
Time frame: 90 days
Incidence of All-Cause Study Medicine Discontinuation or Withdrawal
Time frame: 14 days
Overall symptom severity at 5 and 14 days
Time frame: 5 and 14 days
Overall change in disease severity over 14 days among those who are symptomatic at baseline
Time frame: 14 days
Results and safety
The study was stopped early (reason given: Request of Health Canada after publication of https://doi.org/10.7326/M20-4207). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
- Background: PubMed 32383125Lother 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.
- Results publication: PubMed 32673060Skipper 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.
- Results publication: PubMed 32492293Boulware 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.
- Individual participant dataSharing planned: Yes. De-identified dataset will be included with publication.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Todd C Lee, MD MPH FIDSA principal investigator
Research Institute of the McGill University Health Centre
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydroxychloroquine in people with Corona Virus Infection and SARS-CoV Infection, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Request of Health Canada after publication of https://doi.org/10.7326/M20-4207). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ordinal Scale of COVID19 Disease Severity at 14 days (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04421664, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.