Plain English Summary
Background and study aims
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.
In 2020, the virus has spread to many countries around the world and neither a vaccine against the virus or specific treatment for COVID-19 has yet been developed. As of March 2020, it is advised that people minimize travel and social contact, and regularly wash their hands to reduce the spread of the virus.
Groups who are at a higher risk from infection with the virus, and therefore of developing COVID -19, include people aged over 70 years, people who have long-term health conditions (such as asthma or diabetes), people who have a weakened immune system and people who are pregnant . People in these groups, and people who might come into contact with them, can reduce this risk by following the up-to-date advice to reduce the spread of the virus.
Currently, there are no drugs proven to treat or delay the progression of COVID-19 and no vaccine is yet available. Efforts are underway to repurpose established drugs with well-understood drug interactions and safety profiles. A number of clinical trials have been established at great speed following the onset of the pandemic, but none of these is enrolling participants with significantly reduced kidney function and/or receiving certain kinds of immunosuppressive medicines such as solid organ transplant recipients. Patients receiving in-centre dialysis are at extremely high risk from COVID-19, particularly as they are unable to self-isolate.
The PROTECT trial aims to enrol patients at particularly high risk of COVID-19 and its complications (such as kidney dialysis patients, vasculitis, and transplant patients), seeking to test treatments that either might prevent the disease from occurring or may reduce the number of cases where the disease becomes serious or life-threatening.
Dialysis is a procedure to remove waste products and excess fluid from the blood when the kidneys stop working properly. It often involves diverting blood to a machine to be cleaned.
Vasculitis is inflammation of blood vessels. It causes changes in the blood vessel walls, including thickening, weakening, narrowing or scarring. These changes can restrict blood flow, resulting in organ and tissue damage.
Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. Transplant recipients must take medication to suppress the immune system which puts them at risk of infection.
Who can participate?
Adults over 18 years, in a vulnerable population (dialysis, vasculitis, or transplant) patients with no symptoms of or confirmed COVID-19 diagnosis.
What does the study involve?
Patients will be randomised to receive either oral Hydroxychloroquine (HQC) or standard care. HQC is a widely used anti-malarial drug which has an effect on the immune system and may as an anti-viral agent in this setting.
The PROTECT study has been designed to place the minimum burden on patients, and on the healthcare workers looking after them at this time. They will not have to attend the hospital for any extra study visits but will be asked to complete follow-up questionnaires. There is also a small chance that they may experience one of the side effects of HQC listed in the patient information sheet.
What are the possible benefits and risks of participating?
There is no guarantee that patients will benefit from taking part in this trial. They may be protected from COVID-19 by HCQ, but it is also possible that HCQ may not protect them from COVID-19. The researchers do not yet know if hydroxychloroquine will be an effective medication for these patients. However, information collected as part of their participation in this trial will help other people in the future. If successful, this trial will reduce the burden of infection amongst high-risk patient groups, in a time-efficient and cost-effective manner, and help to ease the pressures on an already strained healthcare system.
Where is the study run from?
Addenbrookes Hospital (UK)
When is the study starting and how long is it expected to run for?
May 2020 to May 2025
Who is funding the study?
April Trust (UK)
Who is the main contact?
Dr Thomas Heistra, add-tr.protect@nhs.net
Dr Kerry Brusby, add-tr.protect@nhs.net
Trial website
Contact information
Type
Scientific
Primary contact
Dr Thomas Hiemstra
ORCID ID
http://orcid.org/0000-0002-2115-8689
Contact details
Cambridge Clinical Trials Unit
Box 401 Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 336817
add-tr.protect@nhs.net
Type
Public
Additional contact
Dr Kerry Brusby
ORCID ID
Contact details
Cambridge Clinical Trials Unit
Box 401 Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 25 4472
add-tr.protect@nhs.net
Additional identifiers
EudraCT number
2020-002016-48
ClinicalTrials.gov number
Nil known
Protocol/serial number
CCTU0307, IRAS282317
Study information
Scientific title
PROphylaxis for paTiEnts at risk of COVID-19 infecTion (PROTECT)
Acronym
Study hypothesis
The use of Hydroxychloroquine (HCQ) prophylaxis in at risk patients (i.e. haemodialysis, vasculitis, and transplant patients) will increase the time to confirmed COVID-19 infection in this at-risk population compared to standard care.
Ethics approval
Not provided at time of registration
Study design
Open-label multi-centre randomized controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Prevention
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet.
Condition
COVID-19 (SARS-CoV-2 infection) in dialysis, vasculitis, and kidney transplant patients
Intervention
Patients will be randomised to receive either 1:1 oral Hydroxychloroquine (HCQ) or standard care (no HCQ). Randomisation will be carried out using a validated bespoke automated randomisation system. Randomisation will be stratified by PROTECT sub-group, age and centre.
Haemodialysis subgroup
Dosing: 600mg per week given as 200mg three times per week after each haemodialysis session for 6 months
Vasculitis and transplant subgroups
Dosing: 800mg for first 2 days followed by 400mg once a week for 6 months
Duration of follow up (all subgroups):
Until the end of the trial, on average 6 months
Intervention type
Drug
Phase
Phase II/III
Drug names
Hydroxychloroquine sulfate
Primary outcome measure
Time to confirmed COVID-19 diagnosis via online questionnaires at 6 weekly intervals
Secondary outcome measures
Duration and severity of illness (including mortality) collected through linkage to medical databases and through review of medical records.
Overall trial start date
03/04/2020
Overall trial end date
03/05/2025
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1.1. Dialysis patients receiving in-centre haemodialysis, or
1.2. Diagnosis of vasculitis (according to Chapel Hill Consensus Conference 2012 definitions) and have received immunosuppression (including prednisolone ≥ 5mg daily and/or an immunosuppressive agent (cyclophosphamide (oral or IV), rituximab, azathioprine, MMF, methotrexate, tociluzumab, alemtuzumab, abatacept, leflunomide) in the last 3 years, or
1.3. Transplant patients that have a functional kidney transplant (updated 15/05/2020, previously: Transplant patients)
2. Aged at least 18 years
3. No previous confirmed COVID-19 diagnosis
4. No symptoms highly suggestive of COVID-19 infection at screening or since 1st March 2020
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
500
Participant exclusion criteria
1. Inability to provide informed consent
2. Hypersensitivity reaction to hydroxychloroquine, chloroquine or 4-aminoquinolines
3. Contraindication to taking hydroxychloroquine as prophylaxis e.g known epilepsy
4. Already taking chloroquine, hydroxychloroquine or 4-aminoquinolines
5. History of any retinopathy including diabetic retinopathy requiring laser therapy
6. Taking medications which are contra-indicated alongside HCQ - Digoxin, Halofantrine, Amiodarone, Moxifloxacin, Cyclosporin, Mefloquine, Praziquantel
7. Known history of prolonged QTc
8. eGFR < 15ml/min
9. Multi-organ transplant recipient (added 15/05/2020)
Recruitment start date
18/05/2020
Recruitment end date
01/12/2024
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Addenbrookes Hospital
Cambridge University Hospitals NHS Foundation Trust
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Trial participating centre
Gloucestershire Hospitals Nhs Foundation Trust
Trust HQ
Alexandra House
Cheltenham
GL53 7AN
United Kingdom
Trial participating centre
Shrewsbury And Telford Hospital Nhs Trust
Mytton Oak Road
Shrewsbury
SY3 8XQ
United Kingdom
Trial participating centre
Basildon and Thurrock University Hospital
Nethermayne
Basildon
SS16 5NL
United Kingdom
Trial participating centre
Kent & Canterbury Hospital
East Kent Hospitals University Nhs Foundation Trust
Ethelbert Road
Canterbury
CT1 3NG
United Kingdom
Trial participating centre
Nottingham University Hospitals NHS Trust
Trust Headquarters
Queens Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
Trial participating centre
Royal Stoke University Hospital
Newcastle Road
Stoke-on-Trent
ST4 6QG
United Kingdom
Trial participating centre
Bradford Royal Infirmary
Bradford Teaching Hospitals NHS Foundation Trust
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom
Trial participating centre
Northern General Hospital
Sheffield Teaching Hospitals NHS Foundation Trust
Herries Road
Sheffield
South Yorkshire
Sheffield
S5 7AU
United Kingdom
Trial participating centre
The Royal London Hospital
Whitechapel Road
Whitechapel
London
E1 1BB
United Kingdom
Trial participating centre
Imperial College Healthcare Nhs Trust
The Bays
St. Marys Hospital
South Wharf Road
London
W2 1BL
United Kingdom
Trial participating centre
St George's Hospital
St George's University Hospitals Nhs Foundation Trust
Blackshaw Road
Tooting
London
SW17 0QT
United Kingdom
Trial participating centre
Royal Liverpool University Hospital
Liverpool University Hospitals Nhs Foundation Trust
Prescot Street
Liverpool
L7 8XP
United Kingdom
Trial participating centre
East Surrey Hospital
Surrey And Sussex Healthcare Nhs Trust
Canada Avenue
Redhill
RH1 5RH
United Kingdom
Trial participating centre
Salford Royal
Salford Royal Nhs Foundation Trust
Stott Lane
Salford
M6 8HD
United Kingdom
Trial participating centre
Sunderland Royal Hospital
South Tyneside And Sunderland Nhs Foundation Trust
Kayll Road
Sunderland
SR4 7TP
United Kingdom
Trial participating centre
Royal Derby Hospital
University Hospitals Of Derby And Burton Nhs Foundation Trust
Uttoxeter Road
Derby
DE22 3NE
United Kingdom
Trial participating centre
St Helier Hospital
Epsom And St Helier University Hospitals Nhs Trust
Wrythe Lane
Carshalton
SM5 1AA
United Kingdom
Trial participating centre
NHS Greater Glasgow and Clyde
J B Russell House
Gartnavel Royal Hospital
1055 Great Western Road
Glasgow
G12 0XH
United Kingdom
Trial participating centre
King's College Hospital Nhs Foundation Trust
Denmark Hill
London
SE5 9RS
United Kingdom
Trial participating centre
NHS Tayside
Kings Croos
Clepington Road
Dundee
DD3 8EA
United Kingdom
Trial participating centre
Queen Alexandra Hospital
Portsmouth Hospitals Nhs Trust
Southwick Hill Road
Portsmouth
PO6 3LY
United Kingdom
Trial participating centre
Leicester Royal Infirmary
University Hospitals of Leicester Nhs Trust
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Trial participating centre
Freeman Hospital
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Freeman Road
High Heaton
Newcastle-upon-tyne
NE7 7DN
United Kingdom
Trial participating centre
Doncaster Royal Infirmary
Doncaster and Bassetlaw Teaching Hospitals Nhs Foundation Trust
Armthorpe Road
Doncaster
DN2 5LT
United Kingdom
Trial participating centre
Royal Devon & Exeter Hospital
Royal Devon and Exeter Nhs Foundation Trust
Barrack Road
Exeter
EX2 5DW
United Kingdom
Trial participating centre
NHS Lanarkshire
14 Beckford Street
Hamilton
ML3 0TA
United Kingdom
Trial participating centre
Arrowe Park Hospital
Wirral University Teaching Hospital Nhs Foundation Trust
Arrowe Park Road
Upton
Wirral
CH49 5PE
United Kingdom
Trial participating centre
Southmead Hospital
North Bristol Nhs Trust
Southmead Road
Westbury-on-trym
Bristol
BS10 5NB
United Kingdom
Trial participating centre
Royal Preston Hospital
Lancashire Teaching Hospitals Nhs Foundation Trust
Sharoe Green Lane
Fulwood
Preston
PR2 9HT
United Kingdom
Trial participating centre
Royal Berkshire Hospital
Royal Berkshire Nhs Foundation Trust
London Road
Reading
RG1 5AN
United Kingdom
Trial participating centre
New Cross Hospital
The Royal Wolverhampton Nhs Trust
Wolverhampton Road
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Trial participating centre
Torbay Hospital
Torbay and South Devon Nhs Foundation Trust
Newton Road
Torquay
TQ2 7AA
United Kingdom
Trial participating centre
Norfolk And Norwich University Hospitals Nhs Foundation Trust
Colney Lane
Colney
Norwich
NR4 7UY
United Kingdom
Trial participating centre
Royal Free Hospital
Royal Free London Nhs Foundation Trust
Pond Street
London
NW3 2QG
United Kingdom
Sponsor information
Organisation
Cambridge University Hospitals NHS Foundation Trust
Sponsor details
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 254472
cctu@addenbrookes.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Organisation
University of Cambridge
Sponsor details
Trinity Lane
Cambridge
CB2 1TN
United Kingdom
+44 (0)1223 337733
researchgovernance@medschl.cam.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
April Trust
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
All publications will be approved by the PROTECT steering group. Reporting of results will be through publication of manuscripts in peer-reviewed journals and oral or poster presentations at relevant National or International meetings. As COVID-19 represents an emerging challenge, interim analyses may be made available via pre-print repositories ahead of publication in peer-reviewed journals or meetings. Audit datasets will be disseminated to relevant organisations with the agreement of the PROTECT steering group.
Important findings may be communicated through local or National media as approved by the PROTECT steering group and Sponsor Communications teams.
All publications will be approved by the PROTECT SG. Reporting of results will be through publication of manuscripts in peer-reviewed journals and oral or poster presentations at relevant National or International meetings.
As COVID-19 represents an emerging challenge, interim analyses may be made available via pre-print repositories ahead of publication in peer-reviewed journals or meetings.
Important findings may be communicated through local or National media as approved by the PROTECT steering group and Sponsor Communications teams.
IPD sharing statement:
The datasets generated during and/or analysed during the current study are available on reasonable request from add-tr.protect@nhs.net
Intention to publish date
01/12/2025
Participant level data
Available on request
Basic results (scientific)
Publication list