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ALBERTA HOPE COVID-19 for the Prevention of Severe COVID19 Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04329611
Recruitment Status : Terminated (Enrolment was suspended on 22may2020, after Mehra et al (Lancet 2020) then stopped due to lack of Covid19 cases.)
First Posted : April 1, 2020
Last Update Posted : July 31, 2020
Sponsor:
Collaborators:
Alberta Health Services
University of Alberta
University of Calgary
Calgary Health Trust
Alberta Innovates Health Solutions
Government of Alberta
Information provided by (Responsible Party):
Dr. Michael Hill, University of Calgary

Tracking Information
First Submitted Date  ICMJE March 29, 2020
First Posted Date  ICMJE April 1, 2020
Last Update Posted Date July 31, 2020
Actual Study Start Date  ICMJE April 13, 2020
Actual Primary Completion Date July 20, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2020)
Composite of hospitalization, invasive mechanical ventilation or death within 30 days [ Time Frame: Within 30 days of randomization ]
The aim of this intervention is to prevent severe COVID-19 disease. This trial aims to confirm that severe COVID-19 disease can be reduced by a relative risk reduction of 50% by the use of hydroxychloroquine.The aim of this intervention is to prevent severe COVID-19 disease. This trial aims to confirm that severe COVID-19 disease can be reduced by a relative risk reduction of 50% by the use of hydroxychloroquine.The aim of this intervention is to prevent severe COVID-19 disease. This trial aims to confirm that severe COVID-19 disease can be reduced by a relative risk reduction of 50% by the use of hydroxychloroquine.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2020)
  • mortality [ Time Frame: Within 30 days of randomization ]
    Mortality within 30 days of randomization
  • Symptom duration [ Time Frame: Within 30 days of randomization ]
    defined as the number of days from randomization to complete symptom resolution, based on public health follow-up and day 7 and day 30 telephone interview (continuous)
  • Disposition at 30 days defined as recovered, ongoing symptoms but not hospitalized, hospitalized, or deceased (categorical) [ Time Frame: Within 30 days of randomization ]
    Disposition of the patient at the Day 30 telephone followup
Original Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2020)
  • composite of invasive mechanical ventilation or death within 30 days [ Time Frame: Within 30 days of randomization ]
    Following patients admitted to ICU for mechanical ventilation for symptoms of COVID19
  • invasive mechanical ventilation [ Time Frame: Within 30 days of randomization ]
    Following patients admitted to ICU for mechanical ventilation for symptoms of COVID19
  • hospitalization within 30 days [ Time Frame: Within 30 days of randomization ]
  • mortality [ Time Frame: Within 30 days of randomization ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ALBERTA HOPE COVID-19 for the Prevention of Severe COVID19 Disease
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of Oral Hydroxychloroquine for the Treatment of SARS-CoV-2 Positive Patients for the Prevention of Severe COVID-19 Disease.
Brief Summary Albertans with COVID-19 are at risk of deteriorating and developing severe illness. Those over age 40 or with co-morbid illness, and likely those who are immune suppressed, are at highest risk. This study will include a focus on people with immune-suppressed states. Individuals confirmed to have SARS-CoV-2 infection will be identified using administrative data (positive lab result, age 18 or over, not hospitalized, and not living in SL4 level of care). They will then be contacted by AHS staff, independent of the researchers, to obtain their consent for the researchers to contact them about this trial. The AHS staff member who contacts the individual will enroll consenting individuals into a study database. If they provided an email address an email will automatically be sent to the individual with study information. Those who decline to be contacted will also be informed of the study website so they can choose to review the study information and self-enrol, although they will need to do so quickly to meet study timelines. Enrolled participants will be contacted by a study coordinator. Those without access to the internet will be informed about the study details when they are contacted by a study coordinator. When the study coordinator contacts potential participants the study will be reviewed, and the potential participant will have an opportunity to ask questions. Consent for participation will be obtained by telephone. Telephone consent will be recorded. Participants will then be screened for inclusion and exclusion criteria by telephone interview and review of Alberta Netcare. Alberta Netcare is the province of Alberta's public Electronic Health Record used to store patient information so that it is easily accessible to healthcare professionals for the purpose of care. Information like immunizations, ECG results, diagnostic images and reports, written medical reports (e.g. surgery reports, consultations, hospital admissions), diagnostic lab testing results (e.g. blood tests, urine tests, blood bank info), allergies and intolerances (drug and food allergies, food intolerances), prescription history, and general patient information (e.g. name, birthdate, personal health number, address, phone number). Those who are not eligible for the study will be informed of the reason(s) for ineligibility (generally it will be a safety exclusion and they should be aware of this). Those who are eligible will be randomized to receive HCQ or placebo for a total duration of 5 days. Study drug will be delivered to their residence by courier. Telephone follow-up will occur at day 7 (range 7-10 days) and at day 30 (range 25-35 days).
Detailed Description

This double-blind placebo-controlled, randomized clinical trial will determine if hydroxychloroquine for 5 days, initiated within 96 hours of confirmation of a positive COVID-19 result, and within 12 days of symptom onset, reduces the occurrence of severe COVID-19 disease. Severe disease is defined as the composite of hospitalization, invasive mechanical ventilation and 30-day mortality. This trial will enrol consenting adults who are not hospitalized, are age 18 or over, have a risk factor for severe disease, have no contraindication to treatment with hydroxychloroquine, can swallow pills, and who do not have a severe underlying comorbidity where treatment is not likely to be beneficial to the patient.

Secondary outcomes will be the proportion of participants requiring hospitalization, invasive mechanical ventilation, 30-day mortality, and disposition at 30 days, defined as recovered, ongoing symptoms but not hospitalized, hospitalized, or deceased.

Randomization will be stratified by age, risk of severe disease, and Alberta Health zone of primary residence. A pre-specified risk classification that includes immunosuppressed status will define those at high risk of severe disease. Health care delivery across Alberta Health zones will likely differ, in part due to the remote location of most patients in some zones.

Alberta has a single publicly funded health care system with processes and administrative data that will allow complete capture of health system encounters and resource utilization. The population is ethnically diverse. In 2016, 23.5% of Albertans belonged to a visible minority group compared with 22.3% for Canada overall (1). Also, in 2018, 94.1% of Albertans age 15 and older used the internet for personal use compared with 91.3% for Canada overall; this excluded full-time residents of institutions (2). This will support a high degree of electronic recruitment and data capture.

The current COVID-19 epidemic has also paused most ongoing research, thus providing access to many experienced researchers and highly trained research staff.

Lack of any proven treatments for this severe condition makes it imperative that we use the resources we have to try to improve the lives of Albertans and determine if there is evidence for the use of hydroxychloroquine for confirmed COVID-19 disease, overall, and in high risk participants.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
Randomization will be conducted using an online tool. The use of an online tool will allow for dynamic randomization which ensures concealment of allocation. We will use a minimal sufficient balance randomization tool to ensure balance on age, sex, risk status (binary variable based on immune competence and other identified risks), days from symptom onset to randomization and provincial health zone (5 categories). These variables will be identified at telephone screening by a study coordinator, clarified with a physician when necessary, and entered into the online randomization tool. It is predicted that many patients will want treatment. Further, immunosuppressed patients may be at the highest risk of fatal outcomes. Therefore, we will use 2:1 randomization (HCQ: placebo).
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
A randomized, double-blind, placebo-controlled trial - trial staff and patients will all be blinded to the treatment allocation.
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE Drug: Hydroxychloroquine
COVID19
Other Name: plaquenil
Study Arms  ICMJE
  • Active Comparator: hydroxychloroquine
    hydroxychloroquine 400 mg po bid loading dose for 1 day followed by 200 mg po twice daily for 4 days
    Intervention: Drug: Hydroxychloroquine
  • Placebo Comparator: Placebo
    Matching Placebo
    Intervention: Drug: Hydroxychloroquine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 29, 2020)
148
Original Estimated Enrollment  ICMJE
 (submitted: March 31, 2020)
1660
Actual Study Completion Date  ICMJE July 20, 2020
Actual Primary Completion Date July 20, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Confirmed SARS-CoV-2 infection, defined as RT-PCR provincial laboratory confirmation.
  2. Self-reported symptoms of SARS-CoV-2 infection including any of the following: fever ≥37.5°C, cough, dyspnea, chest tightness, malaise, sore throat, myalgias, or coryza
  3. Time from a positive test result to day 1 of treatment within 4 days
  4. Time from patient reported first symptoms to day 1 of treatment within 12 days
  5. Adults, age 18 and over, with any risk factor for severe disease
  6. Resident of Alberta or if not a resident of Alberta able to provide complete follow-up data
  7. Agrees to use adequate contraception for the duration of the study
  8. Informed consent

Exclusion Criteria:

  1. Currently or imminently planned admission to hospital
  2. Any contraindication to hydroxychloroquine :

    1. Known hypersensitivity to hydroxychloroquine, chloroquine, or other 4-aminoquinoline derivatives, or any component of the formulation
    2. Known diagnosis of G6PD deficiency or porphyria
    3. Known retinal eye disease with vision impairment, in which hydroxychloroquine is a known contraindication
    4. Known history of QTc prolongation or QTc of > 470 msec (males) or > 480 msec (females) on any ECG within the previous year, if available
    5. Unexplained syncope or family history of long QT syndrome or family history of premature sudden cardiac death at < 50 years of age
    6. Severe diarrhea and/or vomiting or any eating disorders or any persistent vomiting condition
    7. Known significant liver disease including cirrhosis associated with any history of ascites, encephalopathy, or variceal bleeding as per history or medical chart (or Child Pugh B&C) or alcoholic hepatitis
    8. Uncontrolled epilepsy (more than 2 seizures within the previous year or any hospitalizations for status epilepticus within the previous 2 years)
    9. Current use of hydroxychloroquine (Plaquenil), chloroquine, lumefantrine, mefloquine, quinine, artemether, cyclosporine, dapsone, digoxin, and drugs that are known to prolong the QTc as per section 7.5.2.
    10. Score of 7 or more on the Tisdale scale modified such that instead of (1) admission potassium, any known serum potassium within the previous 30 days will be used; if no serum potassium is available the sub-score will be 0, and (2) admission ECG, any known ECG within the previous year will be used; if no ECG is available, the sub-score will be 0; (3) Use of HCQ will be included as one risk factor and anyone concurrently using a medication from the list of drugs known to prolong the QTc will already be excluded. (The other major risk factors for prolonged QTc are sepsis, heart failure, acute myocardial infarction, none of which are likely to be encountered in the outpatient setting).
  3. Participation in an ongoing interventional clinical trial within the previous 30 days
  4. Use of hydroxychloroquine (Plaquenil) or chloroquine, lumefantrine, mefloquine, or quinine within the previous 30 days.
  5. Inability to swallow pills or any other reason that compliance with the medical regimen is not likely
  6. Pregnant or breastfeeding
  7. Severe underlying disease where treatment is not likely to be beneficial to the patient.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04329611
Other Study ID Numbers  ICMJE ABCOV-01 version 1.5
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: 24 months after study close out.
Access Criteria: pending.
Responsible Party Dr. Michael Hill, University of Calgary
Study Sponsor  ICMJE Dr. Michael Hill
Collaborators  ICMJE
  • Alberta Health Services
  • University of Alberta
  • University of Calgary
  • Calgary Health Trust
  • Alberta Innovates Health Solutions
  • Government of Alberta
Investigators  ICMJE
Principal Investigator: Luanne Metz, MD University of Calgary
Study Director: Michael D Hill, MD University of Calgary
PRS Account University of Calgary
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP