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

NCT04329611 | Terminated Phase 3 DMC

• 1 other identifier: ABCOV-01 version 1.5
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 2

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).

Conditions

COVID-19

Keywords

SARS-Cov2; viral pneumonia

Outcome Measures

Primary Outcomes (1)

• Composite of hospitalization, invasive mechanical ventilation or death within 30 days

  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.

  Within 30 days of randomization

Secondary Outcomes (3)

• mortality

  Within 30 days of randomization

• Symptom duration

  Within 30 days of randomization

• Disposition at 30 days defined as recovered, ongoing symptoms but not hospitalized, hospitalized, or deceased (categorical)

  Within 30 days of randomization

Study Arms (2)

hydroxychloroquine

ACTIVE COMPARATOR

hydroxychloroquine 400 mg po bid loading dose for 1 day followed by 200 mg po twice daily for 4 days

Drug: Hydroxychloroquine

Placebo

PLACEBO COMPARATOR

Matching Placebo

Drug: Hydroxychloroquine

Interventions

Hydroxychloroquine DRUG

COVID19

Also known as: plaquenil

Placebo; hydroxychloroquine

Eligibility Criteria

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

You may qualify if:

• Confirmed SARS-CoV-2 infection, defined as RT-PCR provincial laboratory confirmation.
• 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
• Time from a positive test result to day 1 of treatment within 4 days
• Time from patient reported first symptoms to day 1 of treatment within 12 days
• Adults, age 18 and over, with any risk factor for severe disease
• Resident of Alberta or if not a resident of Alberta able to provide complete follow-up data
• Agrees to use adequate contraception for the duration of the study
• Informed consent

You may not qualify if:

• Currently or imminently planned admission to hospital
• Any contraindication to hydroxychloroquine :
• Known hypersensitivity to hydroxychloroquine, chloroquine, or other 4-aminoquinoline derivatives, or any component of the formulation
• Known diagnosis of G6PD deficiency or porphyria
• Known retinal eye disease with vision impairment, in which hydroxychloroquine is a known contraindication
• Known history of QTc prolongation or QTc of \> 470 msec (males) or \> 480 msec (females) on any ECG within the previous year, if available
• Unexplained syncope or family history of long QT syndrome or family history of premature sudden cardiac death at \< 50 years of age
• Severe diarrhea and/or vomiting or any eating disorders or any persistent vomiting condition
• 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
• Uncontrolled epilepsy (more than 2 seizures within the previous year or any hospitalizations for status epilepticus within the previous 2 years)
• 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.
• 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).
• Participation in an ongoing interventional clinical trial within the previous 30 days
• Use of hydroxychloroquine (Plaquenil) or chloroquine, lumefantrine, mefloquine, or quinine within the previous 30 days.
• Inability to swallow pills or any other reason that compliance with the medical regimen is not likely

Sponsors & Collaborators

• Dr. Michael Hill: lead
• Alberta Health services: collaborator
• University of Alberta: collaborator
• University of Calgary: collaborator
• Calgary Health Trust: collaborator
• Alberta Innovates Health Solutions: collaborator
• Government of Alberta: collaborator

Study Sites (2)

University of Calgary/Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

University of Alberta

Edmonton, Alberta, Canada

Location

Related Publications (2)

• Ganesh A, Rosentreter RE, Chen Y, Mehta R, McLeod GA, Wan MW, Krett JD, Mahjoub Y, Lee AS, Schwartz IS, Richer LP, Metz LM, Smith EE, Hill MD; Alberta HOPE COVID-19 Collaborators. Patient-reported outcomes of neurologic and neuropsychiatric symptoms in mild COVID-19: a prospective cohort study. CMAJ Open. 2023 Aug 8;11(4):E696-E705. doi: 10.9778/cmajo.20220248. Print 2023 Jul-Aug.

  PMID: 37553227 DERIVED

• Schwartz I, Boesen ME, Cerchiaro G, Doram C, Edwards BD, Ganesh A, Greenfield J, Jamieson S, Karnik V, Kenney C, Lim R, Menon BK, Mponponsuo K, Rathwell S, Ryckborst KJ, Stewart B, Yaskina M, Metz L, Richer L, Hill MD; ALBERTA HOPE COVID-19 Collaborators. Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial. CMAJ Open. 2021 Jun 18;9(2):E693-E702. doi: 10.9778/cmajo.20210069. Print 2021 Apr-Jun.

  PMID: 34145052 DERIVED

MeSH Terms

Conditions

COVID-19; Pneumonia, Viral

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Luanne Metz, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

• Michael D Hill, MD

  University of Calgary

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: A randomized, double-blind, placebo-controlled trial - trial staff and patients will all be blinded to the treatment allocation.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Co-Principal Investigator

Model Details: 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).

Study Record Dates

• First Submitted: March 29, 2020
• First Posted: April 1, 2020
• Study Start: April 13, 2020
• Primary Completion: July 20, 2020
• Study Completion: July 20, 2020
• Last Updated: July 31, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 24 months after study close out.
• Access Criteria: pending.

Locations

CA (2)