PROphylaxis for paTiEnts at risk of COVID-19 infecTion


The PROTECT-V trial will enrol patients at particularly high risk of COVID-19 and its complications.  The first drug to be tested to see if it might prevent the disease occurring is intranasal niclosamide. Additional treatment arms may be added if further promising treatments become available

PROTECT-V will enrol patients with kidney or autoimmune diseases, including patients undergoing dialysis, kidney transplant recipients, and individuals with auto-immune conditions receiving immunosuppression.  These are vulnerable populations who are underrepresented in many existing clinical trials.

The treatment currently being tested is:

  • Niclosamide – a medication routinely used to treat tapeworm infections, which has demonstrated in vitro action against SARS-CoV2. It is hypothesised that this will disrupt SARS-CoV2 replication and penetration into cells. Niclosamide is typically taken as an oral tablet but PROTECT-V will use a stable liquid formulation (UNI911) via a nasal spray in order to maximise the effect in the nasal lining where SARS-CoV2 initially predominantly replicates. Patients will be randomly assigned to either receive treatment with Niclosamide or placebo and neither the patient nor the trial investigators will know which treatment a patient has been assigned to.

Welcome to the patient area for the PROTECT-V trial website. This trial aims to enrol patients at particularly high risk of COVID-19 and its complications, seeking to test whether intranasal niclosamide might prevent the disease from occurring.

The following provides answers to questions you might have about this trial:

Patient Information Sheet and Informed Consent Form

What is the purpose of the trial?

COVID-19 is an international health emergency which is immediately impacting the lives of all individuals in the UK. There is an urgent need for medicines that can prevent or treat the infection. There are several clinical trials of treatments for COVID-19 underway in the UK, but many of these exclude patients with complex medical conditions or advanced kidney disease. Reasons for exclusion include the presence of existing illness or risk factors, which may make it difficult to interpret results, concerns about potential interactions of a trial drug with usual essential medications, and difficulties finding the correct dose of a trial drug if it is removed by the kidneys. However, because kidney disease and/or many of the medications used to treat patients with kidney diseases or vasculitis affect the function of the immune system, these individuals may be at increased risk of contracting or becoming very ill from COVID-19. We only have limited information available about how COVID-19 affects immunosuppressed patients and patients on dialysis, but we suspect that if an infection occurs, symptoms are more commonly seen than in the general public and therefore, it is important to test medications that may prevent COVID-19 infection specifically in these groups of patients.

The PROTECT-V trial enrols patients on dialysis or receiving immunosuppressive medications. The focus of this trial is on prevention of disease, rather than treatment once disease occurs. This will be measured by comparing if COVID-19 develops in people who take the trial treatment against those who receive a placebo (“dummy”) treatment. 

What is the drug being tested?

The first drug to be tested in the PROTECT-V trial is niclosamide, a common safe drug that has been used in tablet form for tapeworm infections for decades. Preliminary research has shown it may also help protect against COVID-19 infection. However, niclosamide tablets are poorly absorbed from the gut into the bloodstream. Therefore, in the PROTECT-V trial, niclosamide will be administered by a nasal spray directly to the lining of the nose, which is where the virus that causes COVID-19 infection usually first takes hold. This formulation of the drug is unlicensed but has been shown to be safe and well-tolerated in a study of healthy volunteers. In the PROTECT-V trial, participants will receive a total daily dose of 5.6mg of niclosamide administered through a nasal spray (one spray for each nostril) twice daily. This is a much lower dose than the single 2000mg tablet which is taken for tapeworm infections.

Who is being invited to take part?

Patients will be invited to participate in this trial if they have kidney failure and receive dialysis, or are taking an immunosuppressive medication as a result of having a kidney transplant or a diagnosis of vasculitis or glomerulonephritis. We plan to include approximately 1500 participants in total from hospitals across the UK.

Do I have to take part?

Participating in this trial is completely voluntary. If you decide to participate you will be asked to sign an Informed Consent Form, but you will be free to change your mind and leave the trial at any time without giving a reason. If you choose not to participate or to leave the trial, your future medical treatment and normal standard treatment will not be affected in any way.

What will happen to me if I take part?

The following flowchart summarises the trial:

If you agree to participate in the trial, you will sign an Informed Consent Form, and be provided with a copy of this to refer to later.

Screening visit:

After consenting to participate in the trial, you will be asked some questions and have a blood sample taken (not more than 15mls), to confirm that you have not had COVID-19 infection and you can safely receive the trial medication. If you were found to have had COVID-19 in the past or that you cannot be treated with the trial medication, we will let you know and you will continue with your standard treatment, but will not be able to participate in the trial.

Follow up:

Because of the need to avoid extra hospital visits in the COVID-19 pandemic, you will not be required to attend in-person for any trial visits aside from the visit at the start of the trial and the end of the trial. You will be asked to either submit information through online questionnaires, via the PROTECT-V smartphone app, website, by email, post or through telephone calls from your local trial team every week for the first 4 weeks and then every 2 weeks thereafter. You will be asked about any side effects of the trial medication and any possible symptoms of COVID-19 infection. These questionnaires will take about 5 minutes each. You will also need to record all your doses in the dosing diary, in the paper version or the app if you prefer. This will take about 1 minute every day. You will also have to keep all bottles of trial medication until the end of your participation in the trial when you will return these to your trial team.

Your participation in the PROTECT-V trial will last for approximately 6-9 months. The exact duration of the trial depends on how quickly COVID-19 infections occur in the trial population, which is unknown in advance.

What will I have to do?

You will need to comply with the following instructions and restrictions as part of your participation in this trial:

Medication

You will be given a nasal spray that you will have to use in each nostril twice daily following the instructions in the diagram below. If you are using any other nasally administered or inhaled medication (such as asthma medication inhaler), please space the use of the trial medication and any other nasal spray or inhaled medication by at least 1 hour. The trial treatment will continue daily for an average of 6 months, but as an individual, you may receive more or less treatment than this. You can contact the PROTECT-V trial team at any point with any questions, using the contact details at the end of this information sheet.

You may collect your trial treatment during your dialysis sessions or outpatient clinic visits, if possible; otherwise, the local team will send you the trial treatment via courier. If a courier is used, we will share your personal details (name and delivery address) with them to enable delivery of your medication and may check to ensure you have received it. You will need to store your medication in the fridge (between 2-8°C). You will use each medication bottle for a maximum of 14 days, even if there is remaining liquid. Then you will keep the used bottles and cartons at room temperature until the end of your participation and bring them back to your last visit.

You will not be able to participate in any other trials testing medications or vaccines to prevent COVID-19 infection. However, if you are admitted to hospital with COVID-19, your participation in this trial will end, and you can be considered for enrolment in treatment studies.

Questionnaires

Every week for the first 4 weeks, and then every 2 weeks thereafter, all participants in both groups will be asked to answer a short series of questions about your current symptoms, if any, which may be potential side effects of niclosamide (if applicable), or of COVID-19 infection. 

Pregnancy and Breastfeeding

Trial medicines could harm an unborn baby or nursing infant. You will not be able to take part in this trial if you are pregnant or breastfeeding. You will be asked if you are pregnant before starting the treatment, and a pregnancy test will be performed in women of child bearing potential. If, while you are taking the drug, you think you might be pregnant please contact the trial team or your clinician immediately. Your trial doctor will discuss all the options available to you. The outcome and progress of any pregnancy would be followed and you would be asked questions about the pregnancy and baby, if appropriate. These details would also be shared with the manufacturer of the trial medicine for safety reasons.

Contraception

Women who are able to have a baby must use a reliable form of contraception for the entire duration of treatment and for 90 days after your last treatment with the trial drug. This includes any of the following:

•           Oral contraceptive (either combined or progestogen alone)

•           Contraceptive implant, injections or patches

•           Vaginal ring

•           Intrauterine device (IUD, coil or intrauterine system)

•           Condom and cap or diaphragm plus spermicide (chemical that kills sperm)

 

You do not need to use contraception if:

•           You have only one partner, and the man has had an operation to cut the tubes that carry sperm (vasectomy) or

•           You are a woman who cannot become pregnant

•           You are a post-menopausal woman or

•           You practice true abstinence as part of your usual and preferred lifestyle (confirmed negative pregnancy test at screening visit and no sexual activity until 90 days after the last dose of trial medication). If you become sexually active, you must use one of the methods listed above. 

Side Effects (also known as adverse events)

You should tell the trial team if you feel unwell or different in any way. If you have any major concerns or are feeling very unwell please contact your trial doctor immediately using the contact numbers at the end of this information sheet. The common side effects of niclosamide are listed below under point 7 “What are the side effects of the drug being tested?”

Health Insurance

You should discuss your participation in this trial with any insurance provider you have (e.g. travel insurance, health protection insurance, life insurance, income protection, critical illness cover and private medical insurance) and seek advice if necessary, as failure to notify them may affect or invalidate your cover.

COVID-19 guidelines

It is very important that you continue to follow current advice on social distancing and/or shielding and follow any advice issued by your usual clinician or dialysis unit. Should you develop symptoms suggestive of COVID-19 infection (cough, shortness of breath, fever, loss of sense of smell or taste, nausea/vomiting or diarrhoea or any other new symptom concerning for infection), you must arrange a COVID-19 test via the NHS Test and Trace system, booking online or calling 119 to organise an appointment at your nearest testing facility or ask the trial team for a test kit to be sent in the post. You should also request a flu swab at the same time as your COVID-19 test, however, if this isn’t performed by the testing facility you should request a flu testing swab from your trial team. If you are diagnosed with COVID-19 during the trial, then you should follow current guidance with regards to isolation and comply with national contact tracing processes.

What are the side effects of the drugs?

Niclosamide is unlicensed in this formulation. The trial formulation of niclosamide has been tested so far in 36 participants for a treatment period of 2 and a half days in a safety assessment trial. During that trial it has been reported that it can cause mild symptoms after administration potentially including:

  • irritation in the throat
  • cough after inhalation
  • sneeze
  • loss of taste
  • a tingling feeling on the tongue
  • hoarseness 

These symptoms should disappear within 60 to 75 minutes after each dose. If you develop these or other symptoms for a longer period of time, seek medical advice. You should also be aware that the trial treatment is a red-coloured liquid; do not be alarmed if soon after administering the treatment you observe red colouring when blowing your nose. This effect should also disappear within 90 minutes.

You should make sure your doctor or other healthcare professional knows you are participating in this trial before starting any new medicine during the trial. If you experience any serious side effects during the trial, the trial doctor will monitor your health until the side effect has stabilised or resolved. 

What are the possible disadvantages and risks of taking part?

The PROTECT-V trial has been designed to place the minimum burden on you as the patient, and on the healthcare workers looking after you at this time. As this formulation of niclosamide has only been given to a very small number of people to date, there is a chance that you may experience additional side effects other than those listed above.

What are the possible benefits of taking part?

There is no guarantee that you will benefit from taking part in this trial. You may or may not be protected from COVID-19 by niclosamide and we do not yet know if niclosamide will be an effective medication for this indication. However, information collected as part of your participation in this trial will help other people in the future.

What are the alternatives for treatment?

There are currently no known treatments that prevent COVID-19, although there are a number of studies ongoing. If you decide not to participate in this trial, you will continue to receive all your usual care, but will not be given niclosamide as part of this trial.

What happens when the trial stops?

This trial is short, as it is vital that we get an answer quickly in the COVID-19 pandemic. The average time that you will be in the trial is about 6 months. The trial may stop earlier if it becomes clear that the treatment works, or if new information emerges. If this happens, you will be informed by the trial team. If you are diagnosed with COVID-19 and are well enough to stay at home, you will continue treatment for another 28 days. Should you be admitted to hospital, treatment will stop. If the trial finds that niclosamide protects against COVID-19, we hope that niclosamide will be available for ongoing use outside of this trial but we cannot guarantee this. Once the trial is complete, you will continue to receive your usual care, with your usual clinical team.

Will I receive any expenses or payment?

You will not receive any payment for participating in this trial, but we will reimburse travel-related any expenses incurred by your participation in this trial. However, we have kept trial visits to an absolute minimum, and wherever possible they will be scheduled to coincide with your routine hospital appointments.

What if new information becomes available?

Sometimes during the course of a trial, new information becomes available which might affect your decision to continue participating in this trial. In this case, your trial doctor will contact you about the new information to discuss whether you wish to continue participating in PROTECT-V. If you wish to continue on the trial, you will be asked to sign a new Informed Consent Form.

What if I decide I no longer wish to participate in the trial?

You are free to stop participating in this trial at any time. You can do this by speaking to your trial doctor or by indicating your wish to withdraw on the trial smartphone app or website. You do not need to provide a reason, and your decision will not affect your future care or medical treatment. If you decide to stop participating you will no longer receive the trial treatment. You can decide whether you would still be happy for us to continue to collect data remotely from your central healthcare records without receiving any trial treatment or completing the trial questionnaires, or to stop participating in the trial altogether (no data collection from questionnaires or central healthcare records). However, any data already collected about you will continue to be used in the analysis and where possible you will be contacted one month after withdrawal to ask you a short series of questions about your health.

The trial doctor may choose to withdraw you from the trial if they feel it is in your best interests, or if you have been unable to comply with the requirements of the trial. Reasons for trial withdrawal could include:

  • You have experienced a serious side effect
  • You become pregnant
  • The trial doctor feels you are no longer eligible for this trial (e.g. due to a change in your other medications or healthcare)
  • If you develop COVID-19, the trial treatment will be stopped after 28 days if you are well enough to stay at home. If you are hospitalised the trial treatment will stop immediately. This will allow you to enter other trials exploring treatments for COVID-19.
What if there is a problem?

Any complaint about the way you have been dealt with during the trial or any possible harm you might suffer will be addressed. If you have any concerns about any aspect of this trial you should speak to your trial doctor who will do their best to answer your questions.

In the event that something does go wrong and you are harmed by taking part in the research and this is due to someone’s negligence then you may have grounds for a legal action for compensation against Cambridge University Hospitals NHS Foundation Trust (or your hospital – for multicentre trials). If your claim is successful, your legal costs will be met. The normal National Health Service complaints mechanisms will still be available to you (if appropriate).

The NHS does not provide no-fault compensation i.e. for non-negligent harm, and NHS bodies are unable to agree in advance to pay compensation for non-negligent harm. They are able to consider an ex-gratia payment in the case of a claim.

If you wish to complain or have any concerns about any aspect of the way you have been approached or treated during this trial, you can do this through the NHS complaints procedure. In the first instance it may be helpful to contact the Patient Advice and Liaison Service (PALS)) at your hospital.

Will my taking part in this trial be kept confidential?

For participants recruited at Cambridge University Hospitals (where the Sponsor is also the site):

You can find out more about how the Sponsor uses your information using the information below:

For Cambridge University Hospitals NHS Foundation Trust, please visit: https://www.cuh.nhs.uk/corporate-information/about-us/our-responsibilities/looking-after-your- information, or email the Data Protection Officer at gdpr.enquiries@addenbrookes.nhs.uk

Cambridge University Hospitals will collect your name and contact details to contact you about this trial and make sure that relevant information about the trial is recorded for your care, and to oversee the quality of the trial. Individuals from the Sponsor and regulatory organisations may look at your research records to check the accuracy of this trial. Cambridge University Hospitals will pass these details to the Sponsor along with the information collected from you and your medical records. The only people in the Sponsor organisation who will have access to information that identifies you will be people who need to contact you in relation to this trial and to audit the data collection process. Cambridge University Hospitals will keep identifiable information about you from this trial for 15 years after the trial has finished.

For participants recruited at other participating sites:

Your hospital will keep your name, (NHS number) and contact details to contact you about this trial and make sure that relevant information about the trial is recorded for your care, and to oversee the quality of the trial. Certain individuals from the Sponsor(s) and regulatory organisations may look at your medical and research records to check the accuracy of this trial. The Sponsor(s) will only receive information without any identifying information.

All information collected about you as a result of your participation in the trial will be kept strictly confidential. Your personal and medical information will be kept in a secured file and be treated in the strictest confidence.

Once you have agreed to participate in this trial you will be allocated a unique trial number which will be used on all your trial documentation. This number will be linked to your personal information; however, you will only be identified by this unique number in the final trial data. Your consent to the use of your individual-level trial data or your personal data will last for 15 years, does not have a specific expiry date, but you may withdraw your consent at any time by notifying your trial doctor.

In cases where medication has to be sent to you by courier, your local team will pass your contact details and home address to the authorised personnel of the IMP courier company.

We will follow your medical status on an on-going basis for the duration of the trial. This involves collecting, processing, and transferring your personal data (name, gender, date of birth, postcode, and NHS/CHI number) for medical research purposes only. This will be done by sending the named personal data to the national health record organisations mentioned in point 5. For this process to work, it will involve storing some of your personal data on a secure, password-controlled database with access given to only a very small number of delegated PROTECT trial staff. The healthcare organisations’ systems will be asked for information which will then be stored in our database on a computer server housed in a highly secure environment within the University of Cambridge, School of Medicine, disconnected from the internet.

We will need to inform your GP of your participation in this trial so that any medical decisions made by your GP account for any treatment you are receiving as part of this trial.

At the end of the trial, your anonymised trial data may be shared with other researchers outside the University of Cambridge, both in the United Kingdom and abroad to further knowledge on COVID-19. Link anonymised information will also be shared with Union Therapeutics who are supplying the trial treatment for ongoing safety evaluation, which includes adverse events and pregnancy during your participation in the trial. Anonymised information will also be shared with the NHS and the Department of Health as part of our efforts to combat COVID-19. No information will be shared from which you can be identified as an individual, such as your name, NHS number and date of birth. Your anonymised information will only be used by organisations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research. Your information could be used for research in any aspect of health or care and could be combined with information about you from other sources held by researchers, the NHS or government. It will not be used to make decisions about future services available to you, such as insurance. 

We will also ask for your consent to use the information we collect during your participation in this trial for future research. Any future research will have received approval from an Ethics Committee, but you will not be asked to sign another consent form to participate. This is optional, and should you not wish to consent for your data to be used in future research studies, you will still be able to participate in this trial. Cambridge University Hospitals and the University of Cambridge will keep information about you for 15 years after completion of the trial. This is a legal requirement

What will happen to my samples?

To confirm you have not had COVID-19 infection before participating in this trial and to assess whether you have developed immunity against SARS-COVID-2 by the end of the trial, you will have blood samples taken at the beginning and at the end of your participation in the trial. These samples will be identified with your trial number and sent to an external organisation called The Doctors Laboratory Ltd for analysis within one week; once analysed this laboratory will dispose of your samples as per national guidelines. No personal information will be shared with this laboratory.

If you are part of the first 70 dialysis centre participants recruited, you will have 3 extra blood samples taken to assess whether the trial treatment accumulates in your body. These samples will be taken by the local trial team and labelled with your trial number.

Then they will be processed at your site and sent to Cambridge University Hospitals for storage until all 70 sample sets have been collected. The analysis of these samples will be performed by a subcontracted laboratory in the European Union. No personal information will be shared with said laboratory and once analysed, they will be disposed of according to EU law.

If at any point during the trial you wish to withdraw and these blood samples have already been taken, you will have the right to decide whether they can be used as previously explained or they should be disposed as per local guidelines.

What will happen to the results of the trial?

The results of the trial will be anonymous and you will not be able to be identified from any of the data produced. When the results of this trial are available they may be published in peer reviewed medical journals and used for medical presentations and conferences. They will also be published on the EU Clinical Trials Register website, a central registry for all clinical trials conducted in the EU. The EU Clinical Trials Register is accessible to members of the public (www.clinicaltrialsregister.eu/). We will also publish the main findings of the trial on the trial website.

If you would like to obtain a copy of the published results, please contact your trial doctor directly who will be able to arrange this for you. If you have provided an email address when you registered for the trial, we will send you trial newsletters if you wish. This will include trial results when the trial is completed. 

Who is funding the trial?

Funding for the trial is provided by LifeArc, Kidney Research UK, The April Trust, Addenbrooke’s Charitable Trust and the Addenbrooke’s Kidney Patient Association. The trial treatment, and additional financial support is being provided by Union Therapeutics.

Who has reviewed this trial?

All research within the NHS is reviewed by an independent group of people called a Research Ethics Committee, to protect your interests. This trial has been reviewed and given favourable opinion by the Cambridge East Research Ethics Committee. The Medicines and Healthcare Products Regulatory Agency (MHRA) who are responsible for regulating medicines in the UK have also reviewed this trial. The trial has also been reviewed by members of the Cambridge Bio Resource Centre patient and public involvement team.

Welcome to the staff area for the PROTECT trial. Patients on dialysis or receiving immunosuppressive medications may be invited to take part in this trial.

Eligible patients will be randomised using a central web-based randomisation service.

Protocol

Trial Protocol

 

Information coming soon.

Trial Steering Committee (TSC)

Independent Chair: Dr Rupert Beale

Chief Investigator: Dr Rona Smith
 
Members of the Trial Management Group: Dr Wendi Qian (Trial Statistician), Dr Lynne Whitehead (Trial Pharmacist), Daniel Alvarez-Berdugo (Trial Coordinator) and Rakshya Adhikari (Data Manager)
 
Independent Clinician(s) or Scientist(s): Dr Laurie Tomlinson and Dr Charles Ferro
 
Principal Investigators: TBC
 
Independent Statistician: Dr Sofia Villar
 
Non-voting Funder Representative: TBC
 
Sponsor Representative: Mrs Carrie Bayliss
Data Monitoring Committee (DMC)

Chair: Prof Graham Cooke (Imperial College, London, UK)

Other Committee Members: Dr Michael Walsh (Hamilton, Canada) and Dr Mark Glover (Nottingham, UK)

Statistician: Dr Daniel Slade (Birmingham, UK)

 

 

PROTECT-V in numbers

1
Active Sites
63
Patients Enrolled

Chief Investigators


Funders & Sponsors

Sponsor: Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

Funders: LifeArcAddenbrooke’s Kidney Patient AssociationKidney Research UK and UNION Therapeutics


Key Contacts

Clinical Trial Coordinator: Daniel Alvarez-Berdugo

Telephone: 01223 254684 | Email: daniel.alvarezberdugo@addenbrookes.nhs.uk