Preventative treatment for patients at risk of COVID-19 infection (PROTECT)

Plain English summary of protocol

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 (HCQ) or standard care. HCQ 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, Niclosamide, 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. Rona Smith, add-tr.protect@nhs.net
Mr. Francis Dowling, add-tr.protect@nhs.net

Study website

Contact information

Dr Thomas Hiemstra
Scientific

Cambridge Clinical Trials Unit
Box 401 Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

ORCID ID	0000-0002-2115-8689
Phone	+44 (0)1223 336817
Email	add-tr.protect@nhs.net

Dr Kerry Brusby
Public

Cambridge Clinical Trials Unit
Box 401 Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Phone	+44 (0)1223 25 4472
Email	add-tr.protect@nhs.net

Study information

Eligibility

Locations

Countries of recruitment

• England
• Scotland
• United Kingdom

Study participating centres

Sponsor information

Cambridge University Hospitals NHS Foundation Trust
Hospital/treatment centre

Hills Road
Cambridge
CB2 0QQ
England
United Kingdom

Phone	+44 (0)1223 254472
Email	cctu@addenbrookes.nhs.uk
Website	http://www.cuh.org.uk/
"ROR"	https://ror.org/04v54gj93

University of Cambridge
University/education

Trinity Lane
Cambridge
CB2 1TN
England
United Kingdom

Phone	+44 (0)1223 337733
Email	researchgovernance@medschl.cam.ac.uk
Website	http://www.cam.ac.uk/
"ROR"	https://ror.org/013meh722

Funders

Funder type

Charity

Results and Publications

Study outputs

Editorial Notes

11/04/2024: The recent changes made to the study record were because the original project was withdrawn from the HRA/REC approvals process due to the MHRA's non-acceptance of the CTA, mainly attributed to evidence surfacing at that time that the initial IMP lacked efficacy against Covid-19. Subsequently, the project was reconfigured with alternative IMP and resubmitted, maintaining its original objective of exploring prophylactic medications for COVID-19. It remained consistent for all involved. The difficulties of COVID-19 restrictions and the hurried adaptation to remote work compounded the challenges faced during this period. The following changes were made:
1. Niclosamide Ethanolamine and sotrovimab were added as drug names.
2. Study website was added.
3. The target number of participants was changed from 500 to 5000.
4. An acronym was added.
5. EudraCT/CTIS number 2020-002016-48 was replaced with 2020-004144-28.
6. IRAS number 282317 was replaced with 288652.
7. ClinicalTrials.gov number NCT04389359 was replaced with NCT04870333.
8. Ethics approval was added dated 23/10/2020.
12/03/2024: The following changes were made to the trial record:
1. The study hypothesis was changed.
2. The interventions were changed.
3. The inclusion criteria were updated.
4. The target number of participants
5. The exclusion criteria were updated.
6. The plain English summary was updated to reflect these changes.
25/03/2021: The NCT number has been added.
27/07/2020: The following changes have been made:
1. The ethics approval information has been added.
2. The recruitment start date has been changed from 18/05/2020 to 01/10/2020.
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