Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000501943
Ethics application status
Approved
Date submitted
14/04/2020
Date registered
22/04/2020
Date last updated
9/12/2020
Date data sharing statement initially provided
22/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
COVID-19 prophylaxis with hydroxychloroquine in Front-line Health and Allied-Health Care Workers: The COVID-SHIELD Trial
Scientific title
Effectiveness of Prophylactic Hydroxychloroquine on incidence of COVID-19 infection in Front-line Health and Allied Health Care Workers: The COVID-SHIELD Trial
Secondary ID [1] 301007 0
Nil Known
Universal Trial Number (UTN)
U1111-1250-4307
Trial acronym
COVID-SHIELD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 infection 317045 0
Condition category
Condition code
Infection 315212 315212 0 0
Other infectious diseases
Respiratory 315244 315244 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
a) Hydroxychloroquine or placebo to match will be administered orally once daily; 400mg (>=65kg body weight) or 200mg (<65kg body weight);
b) the duration of administration will be for 4 months total;
c) the mode of administration oral capsule;
d) adherence to medication administration will be done via a daily reminder text message. At the completion of the study, study drug accountability will be performed and blood analysis for Hydroxychloroquine at baseline and completion.
Intervention code [1] 317326 0
Treatment: Drugs
Comparator / control treatment
Placebo will be composed of microcellulose capsule
Control group
Placebo

Outcomes
Primary outcome [1] 323470 0
Incidence of COVID-19 using standard PCR analysis for COVID-19
Timepoint [1] 323470 0
Daily during 4 months of intervention period
Secondary outcome [1] 382015 0
Outcomes of COVID-19 infection: Hospitalisation



Timepoint [1] 382015 0
This will be assessed 30 days post COVID-19 onset and will involve using access to participant medical records for hospital admission including length of admission (days).
Secondary outcome [2] 382043 0
Time to development of COVID-19 adjusted for level of exposure:
Exposure level assessed using questions regarding type of work and number of days/hours per week exposed to patients with COVID-19. These questions will be part of an App which the participants will be answering using a e-daily diary.
Timepoint [2] 382043 0
Daily during 4 months of intervention period
Secondary outcome [3] 382045 0
Incidence of COVID-19 among household contacts of HCWs as self-reported by study participant (using ePRO)
Timepoint [3] 382045 0
Daily during 4 months of intervention period
Secondary outcome [4] 382046 0
Incidence and duration of composite symptoms of viral respiratory tract infection:
-Duration of fever, cough, sore throat, runny nose, fatigue, malaise, myalgia and dyspnea as assed by participant using questions on an App platform for participants
Timepoint [4] 382046 0
Daily during 4 months of intervention period
Secondary outcome [5] 382047 0
Incidence of SARS-CoV-2 seroprevalence:
Incidence of SARS-CoV-2 seropositivity will be measured at end of study compared to baseline
Timepoint [5] 382047 0
At the end of study visit
Secondary outcome [6] 382127 0
Outcomes of COVID-19: ICU admission (days) with assisted ventilation (invasive and non invasive)
Timepoint [6] 382127 0
Progression to invasive or non-invasive ventilation in first 28 days for COVID19 infection, the duration of invasive or non-invasive ventilation will be measured in days verified using patient medical records
Secondary outcome [7] 382128 0
Outcomes of COVID19: Death
Timepoint [7] 382128 0
Time to death and mortality at 7, 15, 28 days post COVID19 infection
Secondary outcome [8] 382129 0
COVID19 outcome: Presence of radiological changes consistent with COVID-19
Timepoint [8] 382129 0
This will be measured using radiology screening tests such as chest X-ray (CXR) or CT scan at 7, 15, 28 days

Eligibility
Key inclusion criteria
1. Study participant is willing to provide informed consent
2. Be aged 18-70 years at the time of consent and in good overall health
3. Health care worker at high risk of COVID-19 exposure including doctors, nurses and other allied health care workers (such as physiotherapist, radiographer, speech/occupational therapists, personal services assistants, dentist/dental nurse/dental hygienists, aged care workers, optometrist, in general practice or other health care services or paramedic (ambulance) in the following settings:
• Emergency department
• COVID-19 management teams: Outpatient Clinic
• Inpatient Ward
• Intensive care unit/ High Dependency Unit (HDU) /Operating Theatre/ Recovery
• Groups exposed to aerosol generating procedures: eg. anaesthetics/intubation teams
• Dental Services
• Aged Care Homes
• Optometry Services
• Otolaryngology Services (ENT)
• Occupational & Speech Therapy
• Physiotherapy
• Paramedicine/Ambulatory
• Radiology
• General Practice
• Other Health Care Services Worker

4. Anticipated to be performing clinical duties as a front-line health care worker during the trial period
5. Willing to adhere to study procedures including daily use of mobile electronic portal to report outcomes and adverse events
6. Willing to take drug/placebo as directed and to not take additional hydroxychloroquine or chloroquine during the trial period
7. Willing to provide COVID-19 test results and permission to use the COVID-19 registry at the end of the study to confirm COVID-19 status
8. Willing to report hospitalisations to the study nurse and to have review of medical records and receive follow-up phone calls to determine outcomes of hospitalisations
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Prior COVID-19
2. Presence of any respiratory illness inclusive of fever, cough, dyspnoea, sore throat, rhinorrhoea, nasal stuffiness, headache, myalgia and fatigue
3. Any cardiac arrhythmias, retinal eye disease, liver or kidney disease
4. Any contra-indication to hydroxychloroquine or chloroquine including allergy or hypersensitivity
5. Any concurrent medication which can prolong QT interval
6. Currently taking or planning to self-treat with hydroxychloroquine or chloroquine
7. Immunosuppressive conditions or medications
8. Pregnancy or breast feeding
9. Concurrent participation in other COVID-19 clinical trials
10. Inability to follow study procedures during the trial period
11. Inability to provide informed consent
12. Lack of fluency in the English language as this will impede the ability of the participant to interact with the web-based data collection platform

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involved contacting the holder of the allocation schedule who was "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation.
Randomisation will be performed 1:1 using secured electronic software . There will be block allocation by recruitment site, stratified allocation by age < 40 or >= 40 years and type of work eg, Nursing, Physiotherapist or Paramedic
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
CONSORT guidelines for randomised controlled studies will be used. Basic demographic data between the two arms will be compared using univariable methods as appropriate.
The primary end point will be analysed with an intention to treat (ITT) analysis.
A modified intention to treat analysis (mITT) will also be used as detailed below.
A per protocol analysis will be performed.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
28/04/2020
Actual
20/05/2020
Date of last participant enrolment
Anticipated
31/12/2020
Actual
Date of last data collection
Anticipated
30/04/2021
Actual
Sample size
Target
650
Accrual to date
250
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 16447 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 16448 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [3] 16449 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 16450 0
The Alfred - Melbourne
Recruitment hospital [5] 16451 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [6] 16452 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [7] 16453 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [8] 16454 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [9] 16458 0
Liverpool Hospital - Liverpool
Recruitment hospital [10] 16459 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [11] 16460 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [12] 16898 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 29990 0
3050 - Parkville
Recruitment postcode(s) [2] 29991 0
3065 - Fitzroy
Recruitment postcode(s) [3] 29992 0
3084 - Heidelberg
Recruitment postcode(s) [4] 29993 0
3004 - Melbourne
Recruitment postcode(s) [5] 29994 0
3220 - Geelong
Recruitment postcode(s) [6] 29995 0
3168 - Clayton
Recruitment postcode(s) [7] 29997 0
3144 - Malvern
Recruitment postcode(s) [8] 29999 0
2170 - Liverpool
Recruitment postcode(s) [9] 30000 0
2050 - Camperdown
Recruitment postcode(s) [10] 30001 0
2010 - Darlinghurst
Recruitment postcode(s) [11] 30549 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 305451 0
Government body
Name [1] 305451 0
Federal Government, Department of Health
Country [1] 305451 0
Australia
Funding source category [2] 305468 0
Other
Name [2] 305468 0
Walter and Eliza Hall Institute of Medical Research
Country [2] 305468 0
Australia
Primary sponsor type
Other
Name
Walter and Eliza Hall Institute of Medical Research
Address
1G Royal Parade Parkville Melbourne Victoria 3052
Country
Australia
Secondary sponsor category [1] 305850 0
None
Name [1] 305850 0
Address [1] 305850 0
Country [1] 305850 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305768 0
Melbourne Health Human Research Ethics Committee (HREC)
Ethics committee address [1] 305768 0
Office for Research
The Royal Melbourne Hospital Level 2 South West
300 Grattan Street
Parkville VIC 3050
Australia
Ethics committee country [1] 305768 0
Australia
Date submitted for ethics approval [1] 305768 0
08/04/2020
Approval date [1] 305768 0
22/04/2020
Ethics approval number [1] 305768 0
HREC/63095/MH-2020

Summary
Brief summary
As the world continues to fight the global pandemic of COVID-19, health resources in many Australian hospitals are expected to reach capacity and become overwhelmed. COVID-19 which is caused by the newly identified virus SARS-CoV-2, can result in a severe respiratory illness requiring ventilator support and sometimes lead to death. Front-line health care workers are at an increased risk of becoming infected due to repeated exposure in their occupational role in caring for patients with COVID-19.
There is an urgent need for better drug options for COVID-19 as currently there are no known effective therapies above delivering best supportive hospital intensive care. Hydroxychloroquine is a well-known well-tolerated immune-modulatory drug widely used in rheumatological conditions. It has anti-malarial properties but has also exhibited in vitro anti-viral activity against SARS-CoV-2. It is currently in clinical trials as both a treatment option and as prophylaxis (prevention) for COVID-19.
This large Australian multi-centre randomised double-blind placebo-controlled study aims to evaluate the efficacy of hydroxychloroquine as prophylaxis against COVID-19 in high-risk health care workers. It will enroll 2250 participants who will be randomised in a 1:1 ratio to take hydroxychloroquine orally daily or placebo for 4 months. The primary endpoint will be incidence of COVID-19.
Trial website
https://www.covidshieldtrial.com.au/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101530 0
Prof Marc Pellegrini
Address 101530 0
Walter and Eliza Hall Institute of Medical Research
1G Royal Parade Parkville, Melbourne Victoria 3052
Country 101530 0
Australia
Phone 101530 0
+61 3 9345 2555
Fax 101530 0
Email 101530 0
[email protected]
Contact person for public queries
Name 101531 0
Ms Community relations at WEHI
Address 101531 0
Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville, Melbourne Victoria 3052
Country 101531 0
Australia
Phone 101531 0
+61 3 9345 2555
Fax 101531 0
Email 101531 0
[email protected]
Contact person for scientific queries
Name 101532 0
Prof Marc Pellegrini
Address 101532 0
Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville, Melbourne Victoria 3052
Country 101532 0
Australia
Phone 101532 0
+61 3 93452555
Fax 101532 0
Email 101532 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.