Condition category
Infections and Infestations
Date applied
24/04/2020
Date assigned
14/05/2020
Last edited
20/05/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

http://www.cuh.org.uk/

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

http://www.cam.ac.uk/

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

Publication citations

Additional files

Editorial Notes

20/05/2020: The trial participating centres (after Addenbrookes Hospital) were added. 15/05/2020: The following changes were made to the trial record: 1. The inclusion criteria were updated. 2. The exclusion criteria were updated. 29/04/2020: Trial’s existence confirmed by April Trust