Research project summaries

Early detection of pulmonary exacerbations in non-cf bronchiectasis (BRONCH-EX)

Why do this study?

This Study, funded by a grant from LifeArc, builds on previous studies that have looked at data from people with Cystic Fibrosis by checking (monitoring) their health while they were at home. 

The goal of this observational study is to learn about the use of equipment to monitor health at home in participants who have non-cystic fibrosis bronchiectasis. The main question[s] it aims to answer are:

How acceptable participants find using home monitoring equipment.

To find out if the data collected from home monitoring can help to detect chest infections (exacerbations) before participants get symptoms they are aware of.

This means that they could possibly be treated sooner, may need less treatment, fewer hospitals stays and perhaps need fewer clinic visits.

Information we will collect and how will it help?

Participants will be in the study for 6 months.  

Patients will use equipment to help them monitor their health at home. They will be able to view their home monitoring data on the Breathe RM app which will be downloaded to their smartphone.     

Participants will be provided with -

·     a handheld spirometer to record FEV1 (lung function)

·     a Fitbit, or other compatible activity monitor, to record activity and heart rate

·     a saturation monitor that fits painlessly on the end of the finger to record oxygen levels

·     weighing scales to record weight

·     a mini freezer and pre-labelled sample containers to store a daily sputum sample. There is enough room    in the freezers for samples to be brought to routine clinic visits. We will provide a cool bag and freezer packs for this. A courier collection of the samples can be arranged if necessary.

Participants will be encouraged to perform lung function, activity and oxygen levels at least 4 x per week.

Participants will be guided through how to set up and use each piece of equipment by the research team. The devices all connect to a smartphone app called Breathe RM (free to download) via Bluetooth. Once set up using the home monitoring devices and adding notes to the app should take no more than 15 minutes per day.

Participants will be asked to record in the app -

·     episodes of pulmonary exacerbation that require antibiotic treatment

·     their coughing and wellness scores daily

Patients are also asked to complete some questionnaires about their quality of life during the study.

How many and how will patients be recruited?  Where will the study take place?

The study will include 50 adult patients who are 18 years old or over, have no-cystic fibrosis bronchiectasis and are able to do some health checking at home.

The study will take place at:

·       Royal Papworth Hospital, Cambridge

What will happen to the findings of the study?

The clinical research team plans to publish the results in scientific journals and to present the results at scientific meetings.

Participants of the study will be informed of the results by newsletter.

Where can I find out more about the study?

For further information, you can speak to one of the clinical research team: Dr Charles Haworth Principal Investigator 01223 638000 or Lucy Gale Clinical Project Manager 01223 638480 lucy.gale1@nhs.net

Analysis of remote monitoring/virtual clinic data in adult patients with Cystic Fibrosis (CF).

Why do this study?

This Cystic Fibrosis Trust funded study looks at information collected in the patient’s home (home monitoring) and virtual (computer generated) clinics to find out how much such treatment costs (whether it is financially more sense to use this rather than what is being offered at the moment) and to understand how the patient finds monitoring their health at home.  The data collected will be analysed to see if the start of a chest infection can be detected before a patient gets symptoms they are aware of. Treatment can then be started earlier which may reduce long term lung damage.

Information we will collect and how will it help?

The study will last 5 years and patients will share their home monitoring / virtual clinic information by using an app called the “Breathe RM App”.  This app can be downloaded onto patients’ smartphones and allows the study team to also collect and analyse information (data) from their:

·        FitBit – a device that people can wear around their wrist to measure their daily steps, heart rate, and more.

·        Pulse oximeter – used to measure the oxygen level (oxygen saturation) of the blood.

·        Spirometer – instrument for measuring how much air can be breathed in and out.

·        Weight Scales.

The data can then be uploaded to the app every day.  Patients will also complete a study specific questionnaire at 3,12 and 24 months into the study.   This will allow the study team to collect feedback from patients to see what it is like taking part in this study, they may also be able to take part in interviews using audio or video recordings.

The following clinical data, on top of gender, is also collected: date of birth, age, height, weight, predicted FEV1[1], and the genetics linked to their Cystic Fibroses.  As well as:

1)     Modulator Therapy - designed to correct the malfunctioning protein made by the CFTR gene

2)     The number of times patients were admitted to hospital

3)     Number of days of antibiotic treatment Clinic Visits - Regular and any extra ones

4)     Any unplanned contact with CF care team

5)     Clinical pulmonary tests - that show how well the lungs are working

6)     Clinical Bloods (CRP levels) to check for infections

7)     Clinical Weight measurements

8)     Microbiology results from sputum (spit) samples

How many and how will patients be recruited?  Where will the study take place?

This is study hopes to recruit 610 patients and will take place at:

·        Royal Papworth Hospital, Cambridge

·        University Hospital Llandough, Cardiff, Wales

·        Queen Elizabeth University Hospital, Glasgow Scotland

·        Western General Hospital, Edinburgh, Scotland

What will happen to the findings of the study?

Results of this trial will be submitted for publication in a peer-reviewed journal by the study team.

The results of what we discover will be published ‘open-access’[2], ‘peer-reviewed’[3] medical journals and presented at international clinical and scientific meetings.  This way we hope to make the findings available to as many people as possible.

We will also let study participants know the main findings of the study via newsletters. Once the study is finished and the results are known participants will be informed by newsletter.

We hope results will start to become available in[GL1]  2025.

Where can I find out more about the study?

Professor Andres Floto Principal Investigator arf27@cam.ac.uk or Lucy Gale Clinical Project Manager lucy.gale1@nhs.net

[1] forced expiratory volume in 1 second (FEV1) is the maximum amount of air that the patient can breathe out during the first second following maximal inhalation

[2] ‘Open-access’ = publications that make research information available to readers at no cost, as opposed to the traditional subscription model in which readers have access to scholarly information by paying a subscription (usually via libraries).

[3] ‘Peer-reviewed’ = is the evaluation of work by one or more people with similar competencies as the authors of the work.  It is a form of self-regulation by qualified members of a profession.

 [GL1]2025

Quality of Life After Cardiac Surgery (QUACS) 

Why do this study?

During the last 20 years, heart surgery has become much safer.  As a result, greater numbers of elderly and frail patients are being offered more complex operations for various heart problems to improve their survival and improve their quality of life.  However, quality of life is not always improved for all who undergo heart surgery.

Although we can now measure the risk to life of having or not having the operation, we don’t fully know the quality of life the patient can expect to have after their operation.  As quality of life is of great importance to patients, surgeons want to be able to give patients good information as to what they can expect after they have been operated on.   This study is hoping to collect such information as that will enable patients to make as full an informed decision whether they want to go ahead with major heart surgery.

Information we will collect and how will it help?

Quality of life information is collected using a simple questionnaire both before the operation and then monthly after it for 12 months. 

We hope that the evidence collected will help surgeons evaluate and inform patients more accurately what they may expect immediately after the surgery, how long it will take them to recover to the same quality of life they had before surgery(if at all) or if    the surgery has provided them with an improved quality of life.  In other words, was the surgery ‘worth it’, what proportion of patients feel this way, and will we ultimately be able to predict who will benefit from surgery and who will not?

The results should help doctors provide the best medical advice to patients, which should reduce potential harm to patients and help them make better informed decisions whether they want to go ahead with heart surgery or not.

How many and how will patients be recruited?  Where will the study take place?

This study is now closed to recruitment but patient follow ups will continue until February 2024.

The study has recruited 2,826 English-speaking patients nationally who were due to have routine or urgent cardiac (heart) surgery.  Medium-risk and high-risk patients on the surgical waiting list were invited by their clinical care team to consider taking part in the study.

What will happen to the findings of the study?

The results of what we discover will be published in

'open-access’[1], ‘peer-reviewed’[2] medical journals and presented at international clinical and scientific meetings.  This way we hope to make the findings available to as many people as possible.

We will also invite participants to attend a presentation of the results at the hospital or by video conference.

This study is now closed to recruitment but patient follow ups will continue until February 2024.

Where can I find out more about the study?

Email: papworth.study.quacs@nhs.net

[1] ‘Open-access’ = publications that make research information available to readers at no cost, as opposed to the traditional subscription model in which readers have access to scholarly information by paying a subscription (usually via libraries).

[2] ‘Peer-reviewed’ = is the evaluation of work by one or more people with similar competencies as the authors of the work.  It is a form of self-regulation by qualified members of a profession.

Nasal High-Flow Oxygen Therapy After Cardiac Surgery (NOTACS)

Why do this study?

Patients with pre-existing lung conditions undergoing open heart surgery may be at high risk of postoperative lung complications and sometimes require additional breathing support. They may need a tight fitting mask to help them breathe and ensure that enough oxygen gets into their blood and carbon dioxide is removed.

High-flow Nasal Oxygen Therapy (HFNT) provides warmed humidified oxygen (air that is warmed and contains some moisture). It assists breathing and may improve patient recovery. The device provides a higher flow of air and oxygen gas mixture to patients than the standard oxygen therapy. This makes it safe and means that it doesn’t dry out airways. 

The High-flow Nasal Oxygen Therapy also provides positive airway pressure, which may be beneficial and help patients’ recovery. It does not require a facemask, and so is considered more comfortable. Patients can also eat normally and speak freely whilst using it, as can patients who receive standard oxygen therapy. High-flow nasal oxygen therapy is administered via a soft nose piece, held in place by an adjustable elasticated band.

The aim of this study is to evaluate whether the use of HFNT after open heart surgery in patients who may be at high risk of developing post-operative breathing complications (e.g. chest infection, collapsed lung) can have a positive effect on a patient’s number of days alive and out of hospital after surgery and help them to get back to normal activities more quickly than patients who are treated with our current standard treatment, i.e. Standard Oxygen Therapy through a facemask or nasal prongs.

The study also aims to compare the cost of HFNT therapy and Standard Oxygen Therapy from the point of the patient and NHS.

As such, before HFNT is recommended for routine NHS use in cardiac surgery patients at high risk of lung complications, the study needs to determine whether it improves patient-related outcomes and is cost-effective in a UK setting.

Information we will collect and how will it help?

On admission for surgery, patients will be asked to complete two quality-of-life questionnaires and a questionnaire collecting information about their usual living abode, health service and medication use.

On the day of surgery, the anaesthesia and surgical procedure will go ahead as usual.  There will be no interventions or changes to the operation planned.  During surgery, patients will be randomly allocated to receive either the HFNT or Standard Oxygen Therapy for when they are woken up after surgery.  This is done during surgery so that the research team will not be able to inform the patient of their allocated therapy before their surgery.

As patients are woken from surgery, the intensive care nurses and doctors will administer the therapy allocated for a minimum of 16 hours after surgery. If doctors feel that longer support or oxygen therapy would be more supportive, this will be given.

At discharge, the patient will be asked to complete the same questionnaires completed before surgery.  Patients also have to complete a paper patient location and medication diary at home for the first 90 days after their surgery. This patient diary collects information on their living location and medication after discharge. 

The quality-of-life questionnaires and a health service and resource use questionnaire will again need to be completed at 30 and 90 days after surgery online or over the telephone with a member of the central research team. 

At 90 days after surgery, participation in the study will finish.

How many and how will patients be recruited?  Where will the study take place?

To assess the effect of HFNT, the study will be recruiting a minimum of 850 patients from 10 UK cardiothoracic centres including Royal Papworth Hospital, Royal Brompton Hospital and Cardiff & Vale University Health Board. The study will also be recruiting patients from 8 hospitals in Australia and 1 hospital in New Zealand. The study is funded by the NIHR HTA and is sponsored by Papworth Trials Unit Collaboration (PTUC).

What will happen to the findings of the study?

The results of the study will be published ‘open-access’[1], ‘peer-reviewed’[2] medical journals and presented at international clinical and scientific meetings.  This way the study team hope to make the findings available to as many people as possible.

The study team also plan to inform patients that took part in the study of the results at the end of the study.

Where can I find out more about the study?

If you wish for further information regarding the study, please do contact the NOTACS study team either by email (papworth.NOTACSstudy@nhs.net) or via telephone 01223 639713

[1] ‘Open-access’ = publications that make research information available to readers at no cost, as opposed to the traditional subscription model in which readers have access to scholarly information by paying a subscription (usually via libraries).

[2] ‘Peer-reviewed’ = is the evaluation of work by one or more people with similar competencies as the authors of the work.  It is a form of self-regulation by qualified members of a profession.

Second Primary Lung Cancer CoHORT Study - SPORT

Why do this study?

This Cancer Research UK funded, observational, study will look at the long-term survival from ‘non-small cell lung cancer’ in England.  Survival has nearly doubled over the last fifteen years mainly because more operations being performed for early-stage lung cancer.  However, if we want to make further improvements in survival rates, we will need to find new ways to help diagnose patients at an even earlier stage than we can at this time.

Recently we have been able to show that lung cancer survivors have a 2-3 times greater risk than the general population of developing another primary cancer in the 10 years after their first cancer was diagnosed.  Up till now, studies have often used samples collected from patients after they had been diagnosed with disease.

Therefore, we want to find out whether we can develop new blood tests that will tell us in advance who is at highest risk of developing another cancer. If we can develop a new test, we hope to be able to use this in the future to try and prevent lung cancer survivors from getting further cancers.

Information we will collect and how will it help?

The research team will collect extra research blood samples from those who take part in the study.  This will ideally be done every 6 months for up to 5 years, in the first instance.   These blood samples will be used to do a variety of tests that will hopefully help to develop a better and more sensitive test for diagnosing cancer at an earlier point in time than we are currently able to.

Additionally, the team will collect clinical information and x-ray or scan reports that are part of normal clinical care as well as any left-over biopsy material from samples routinely taken. 

The samples will be used to look for proteins in the blood and for genetic changes that may influence cancer genes and for other signs that might suggest early stages of cancer.

We intend to collect all of this information during normal clinical appointments wherever possible.

How many and how will patients be recruited?  Where will the study take place?

The study will recruit 850 adult patients who had treatment at least 2 years ago with the aim to cure their primary lung cancer by using surgery, radiotherapy, or a combination of chemotherapy and radiotherapy (also known as chemoradiotherapy). 

Patients will be recruited from participating UK NHS centres in Cambridge, Glasgow, Manchester, Norwich and Nottingham between 1 December 2019 and 31 December 2022, in the first instance.

What will happen to the findings of the study?

The results of what we discover will be published ‘open-access’[1], ‘peer-reviewed’[2] medical journals and presented at international clinical and scientific meetings.  This way we hope to make the findings available to as many people as possible.

Where can I find out more about the study?

Contact the study Chief Investigator:

Professor Robert Rintoul or the study email papworth.sportstudy@nhs.net

[1] ‘Open-access’ = publications that make research information available to readers at no cost, as opposed to the traditional subscription model in which readers have access to scholarly information by paying a subscription (usually via libraries).

[2] ‘Peer-reviewed’ = is the evaluation of work by one or more people with similar competencies as the authors of the work.  It is a form of self-regulation by qualified members of a profession.

Study Title: Site of disease BIOmolecule capture and analysis in PATienTs with established coronary disease undERgoing iNtracoronary assessment

The BIOPATTERN Study

Why do this study?

The purpose of the study is to look at a new device that can collect blood from precise points within coronary blood vessels. The device is a small tube which will be inserted into the appropriate coronary artery and that will mix and collect four small blood samples from either side of a narrowing in the blood vessel in patients who have coronary artery disease (CAD).

The collected blood will then be analysed to see what it contains and how it may be different from other samples collected. Numerous different biomolecules (components of blood that do many different things in the body) can accurately be measured in the blood that can help us better understand the disease. The hope is that by carefully studying the number and type of biomolecules present in different patients with coronary artery disease (CAD), it may lead to improved ways of treating the disease.

Before a new device like the one being used in this study can be used clinically, it needs to go through several rigorous studies to ensure primarily that it is safe and is also effective.  The ‘version 1’ device used to establish these initial safety and efficacy criteria has been updated and modified to a second ‘version 2’ device to improve the way it is manufactured and its ease of use.  

Building on the safety and efficacy data from the ‘version 1’ device, it is the ‘version 2’ device that will be used in this study.

This study will look at the performance of the ‘version 2’ device in 300 patients from NHS hospitals across the UK. Safety data on the ‘version 2’ device will be carefully monitored throughout this study.

Information we will collect and how will it help?

There are 2 screening phases to this study.

Screening Phase 1

The study is aimed at patients who have coronary artery disease and need an invasive (surgical) diagnostic procedure that involves a coronary angiogram (a test to find out if you have a blockage in a coronary artery) and who may, or may not, also need a stent (a tube put inside a blood vessel to help heal or improve the blockage).

During this first phase the study we will recruit patients who, after carefully weighing up all that taking part in the study involves, decide they want to take part.  This group of patients will then be measured for height, weight and have their blood pressure checked.  The patients’ date of birth, sex and ethnicity will also be noted, a questionnaire will be completed, and the researchers will check the patients most recent ECG (electrocardiogram - a simple test that can be used to check the heart's rhythm and electrical activity).

At the time of the diagnostic procedure the doctor decides whether the patient has a coronary artery suitable for using the new device.

Phase 2

• For those patients who will receive the new device, the doctor will use a light-based intracoronary imaging catheter called OCT (Optical Coherence Tomography) introduced over a guide wire to assess the coronary artery of interest. The OCT catheter will then be removed, and the image data will be saved and analysed later.
• The doctor will then insert the new blood sampling catheter into the same coronary artery, which will mix and collect 4 small 2ml blood samples from the blood vessel, again for later analysis.
• The doctor will then remove this blood sampling tube and your procedure will continue as per usual clinical care.

Patients will then be followed up at 30 days to see how they have been feeling and answer some further research questions.

What will happen to the findings of the study?

The results will be published in ‘open-access’[1], ‘peer-reviewed’[2] medical journals and presented at international clinical and scientific meetings.  This way we hope to make the findings available to as many people as possible.

We will also let study participants know the main findings of the study via a final trial summary report.

We hope results will start to become available within 5 years from the end of the trial. 

Where can I find out more about the study?

Kat Bullock: Senior Clinical Trial Co-ordinator 01223 639853

Clare East: Senior Clinical Trial Co-ordinator 01223 639817

[1] ‘Open-access’ = publications that make research information available to readers at no cost, as opposed to the traditional subscription model in which readers have access to scholarly information by paying a subscription (usually via libraries).

[2] ‘Peer-reviewed’ = is the evaluation of work by one or more people with similar competencies as the authors of the work.  It is a form of self-regulation by qualified members of a profession.

Phase ll, Open label study of a Nebulised Nitric Oxide generating liquid in patients with Mycobacterium Abscessus Pulmonary Disease – RESP301-003 (NOMAB)

Why do this study?

This study is funded by ’30 Respiratory and will assess the effectiveness of a new drug (RESP301) in treating patients with Mycobacterium Abscessus (M. Abs) pulmonary disease (MAP). .  It will also measure the safety and patients’ ability to tolerate a fine spray for inhalation (an inhaler of nebulised nitric oxide generating liquid: RESP301) in these patients

This is being investigated as MAP lung infection is increasing in people with CF and other types of lung disease, and it is particularly difficult to treat because of its resistance to most antibiotics.  Treatment can last for more than 18 months and can have unwanted side-effects.

Laboratory based studies show that nitric oxide (NO) is very effective at killing M. Absas well as other bacteria. The inhaler would be taken three times a day and produces NO in the lungs where the infection is located. 

NO is already used in the US to treat other lung conditions.  However, RESP301 specifically has potential advantages over directly inhaled NO gas, because:

a)     it is inhaled three times a day rather than continuously,

b)     it generates greater levels NO directly in the lung where the infection is located, and

c)     it produces fewer waste gasses.

Information we will collect and how will it help?

Participants will be part of the study for 18 weeks and we will collect:

On day 7 of the 14-day lead-in period baseline information

•               a medical history,
•               perform physical examinations,
•               a lung function test,
•               how much NO is exhaled,
•               blood tests and analyses,
•               a sample of sputum (spittle).

   At this stage participants would also be asked to start to           monitor and record some information themselves which           they will continue to do at home each day while they are         on the trial, such as:

•               oxygen levels and other lung test results,
•               heart rate,
•              activity level,
•              weight,
•              how well they feel,
•              how much and how badly they cough,
•              and, if possible, collect and store daily sputum                 samples.

On day 1 of the 28-day treatment period

an overnight stay at the Royal Papworth Hospital to monitor participants as they receive their first 4 doses of RESP301 and safety level checks are carried out after each dose, such as blood tests, the amount of air participants can exhale (spirometry) as well as measuring their NO levels

The results from these will show us who should continue with the treatment and who should not

If the safety checks do not show any significant adverse effects from the treatment, participants are invited to            continue the study at home

Regular clinical reviews will be undertaken by the study team to ensure participant safety and well-being

while at the hospital further baseline information will also be collected like those described above to see if there have been any changes while regular monitoring also continues.

84-day follow-up observation period to see what changes there may be during this time after treatment has finished

Regular monitoring, including clinical reviews, will continue for 12 weeks after the treatment period has finished

Participants will also be asked to continue to take some physiological measurements and produce sputum samples at home, once a week.

How many and how will patients be recruited?  Where will the study take place?

We aim to recruit 12 patients to participate in the study.

What will happen to the findings of the study?

The results of what we discover will be published in ‘open-access’[1], ‘peer-reviewed’[2] medical journals and presented at international clinical and scientific meetings.  This way we hope to make the findings available to as many people as possible.

We will also let study participants know the main findings of the study via a  final Newsletter in 2024 when the trial will have been completed. 

Where can I find out more about the study?

Email: Beth Haines, Clinical Project Manager

[1] ‘Open-access’ = publications that make research information available to readers at no cost, as opposed to the traditional subscription model in which readers have access to scholarly information by paying a subscription (usually via libraries).

[2] ‘Peer-reviewed’ = is the evaluation of work by one or more people with similar competencies as the authors of the work.  It is a form of self-regulation by qualified members of a profession.

ACE-CF(Artificial intelligence to Control acute pulmonary Exacerbations in Cystic Fibrosis)

Why do this study?

This Study, funded by a grant from the National Institute of Health & Social Care (NIHR) and LifeArc, builds on previous studies that have looked at data from people with Cystic Fibrosis (CF) by checking (monitoring) their health while they were at home. This study takes that work further and uses Artificial Intelligence (AI) to predict when someone is at risk of developing a chest infection before they develop symptoms that they would normally be aware of. This means that they could possibly be treated sooner, may need less treatment, fewer hospitals stays and perhaps need fewer clinic visits.

The main purpose of this study is to see if the Breathe RM Signal app, which has been developed from these previous studies improves quality of life, is good at predicting when someone is becoming unwell and is safe to use. Breathe RM Signal helps patients make decisions about their health. If the results are positive, the app will be made available to all people with CF.

 Information we will collect and how will it help?

The study takes place over 1 year.  

Patients share data that they collected at home before this study and use equipment to help them monitor their health at home. They are in one of two groups:

·       Group 1 will be able to view their home monitoring data on the Breathe RM app.

·       Group 2 will be able to view their home monitoring data on the Breathe RM app and be able to view Breathe RM Signal which helps to detect the start of a chest infection and uses data entered by the patients themselves based on how they feel.

Patients use a FitBit or other compatible activity monitor to collect data.  They are also asked to use a ‘pulse oximeter’ to measure blood oxygen levels, a ‘spirometer’ to measure lung function, use weighing scales and add “cough” and “wellness” scores to the app.

Patients are also asked to complete some questionnaires about their quality of life during the study and how they have found using the app / Breathe RM Signal.  They are also invited to take part in focus groups to provide more detailed information about how they have found using the Breathe RM app or Breathe RM Signal.

How many and how will patients be recruited?  Where will the study take place?

The study hopes to include 400 adult patients who are 18 years old or over, have CF and are able to do some health checking at home.

The study will take place at:

·       Royal Papworth Hospital, Cambridge

·       University Hospital Llandough, Cardiff, Wales

·       Queen Elizabeth University Hospital, Glasgow Scotland

·       Western General Hospital, Edinburgh, Scotland

·       Kings University Hospital, London

·       Queens University Hospital, Belfast

·       University Southampton Hospital

·       St James's University Hospital, Leeds 

·       Wythenshaw Hospital, Manchester 

·       Nottingham University Hospitals, City Hospital 

What will happen to the findings of the study?

The clinical research team plans to publish the results in scientific journals and to present the results at scientific meetings.

Participants of the study will be informed of the results by newsletter.

Where can I find out more about the study?

For further information, you can speak to one of the clinical research team: Dr Charles Haworth Principal Investigator 01223 638000 or Lucy Gale Clinical Project Manager 01223 638480 lucy.gale1@nhs.net.

HICC Study: Humoral Immune Correlates of COVID-19

Royal Papworth Hospital has been leading on a national project called Humoral Immune Correlates of COVID-19 (HICC Study). Papworth are collaborating on this study with the University of Cambridge, along with a wider team of scientists (the HICC Consortium) and have been awarded a grant of £1.5 million from the National Institute for Health Reasearch. The HICC Study was set up early in the COVID-19 pandemic and began recruiting in April 2020.

The two main cohorts for this study are Healthy Volunteers (Papworth staff) and COVID-19 Patients from Papworth and four other NHS Trusts around the country. Study participants have been donating blood samples and swabs along with their clinical data for up to one year.

The team is investigating how the immune response differs in patients with asymptomatic, mild, moderate and severe disease, and why some individuals are more susceptible to severe disease than others.  A vaccination arm is exploring vaccine response in our healthy volunteers and patients. The HICC team are also exploring how the immune response differs following infection compared with vaccination, the impact of pre-vaccination exposure, and whether the immune response to vaccination differs in at risk groups. This will help us to develop test and therapies and to predict who might become severely ill with COVID-19.

We completed follow-up of our participants in May 2022, having recruited a total of 988 patient and staff volunteers, and are now working on publishing our results.

      CCP-UK Patient Data Notification

The purpose of this document is to inform our participants about how their data is used in our study.

What is CCP-UK?

 The CCP-UK (Clinical Characterisation Protocol – United Kingdom) is a study that collects information about infectious diseases and potential exposures of public health importance quickly and efficiently in response to potential public health crises. The study was activated in January 2020 in response to the emergence of what was then called Wuhan Flu, which led to the COVID-19 pandemic. Since being activated, we have recruited over 300,000 patients to the data collection aspect of our study. CCP-UK is the largest study of its kind answering questions about COVID-19 in the world. We have also been activated for UK cases of Ebola, Monkeypox, Lassa Fever, Middle East Respiratory Syndrome (MERS) and for Children with severe Hepatitis.

What data do we collect?

 Research nurses and medical students at hospitals across the UK recruited people who tested positive for COVID-19. The research nurses and medical students recorded information on patients’ hospital stay, such as whether they had any underlying conditions, what medicine they were given and what the result of their hospital stay was (discharged well, discharged disabled or death). 

The research team then input this information into our study database. Each patient is given a unique participant ID. No names are stored on the database and individuals cannot be directly identified.

Participants’ date of birth, NHS number and postcode are also recorded on the database. This information is hugely important for the study, which is why we cannot leave it out for confidentiality purposes. Date of birth is important to allow us to analyse the impact of age on COVID-19 outcomes. NHS numbers are important as these let us link to other NHS databases to obtain further information, such as which of our participants received a particular drug to treat COVID-19, or who has received a COVID-19 vaccine. Postcodes are important to allow us to analyse the impact of deprivation factors, such as living in a poorer area, on COVID-19 outcomes. Without these key pieces of information, we wouldn’t be able to complete most of the analysis that we have done and would not have been able to have the same positive impact on the UK’s COVID response.

Why are we allowed to collect this data without consent?

 In March 2020, in order to boost the UK’s response to COVID-19, the Department of

Health and Social Care served the NHS with a COPI (Control of Patient Information Regulations 2002) Notice, requiring them to share confidential patient information without consent for specific purposes. These specific purposes included research on COVID-19. Because of the COPI Notice, our study has been collecting data from patients admitted to hospital in the UK with COVID-19 without getting their permission first.  After expiry of the COPI Notice on 30^th June 2022, the study will continue collecting data without consent under Section 251 Regulation 5 of the National Health Service Act 2006 with support from the Confidentiality Advisory Group (CAG reference: 21/CAG/0125). 

Being able to collect this data without obtaining permission has been very important in enabling our study to achieve what we have done. Many of the people admitted with COVID-19 were too sick to give consent themselves and because of COVID-19 precautions, they were not accompanied by relatives who could speak for them. Because we were not required to obtain consent from each of our participants, we have been able to recruit many more participants than usual and we were able to include the sickest patients who are often missed from studies like ours. We have also been able to work very quickly. Because of this, our data has been able to capture what is happening with COVID around the UK in near real-time. This allowed us to provide the health policy teams and doctors in the NHS with the most up-to-date information to guide the health response throughout the pandemic.

What has the study achieved?

 Because we have been able to collect and analyse this data quickly and efficiently, we have been able to achieve a lot through our study.

·       We provide reports to SAGE and NERVTAG weekly.       These are the committees that provide advice to health and social care policy makers for the UK COVID-19 response.

·       We have been able to identify several risk factors in the UK population that are strongly associated with poor outcomes in COVID-19, including the impact of obesity, respiratory conditions and different outcomes between ethnic groups.

·       We have been able to provide data supporting identification of high-risk groups for COVID-19 vaccination which meant they were given priority and this saved lives.

·       We have been able to conduct research into the usefulness of COVID-19 drugs treatments and shown what works well and what does not.

This all meant the people most likely to benefit from treatments and vaccines were identified in time to benefit and this saved many lives.

You can review these outcomes at our website: https://isaric4c.net/outputs/.

How is the data collected kept safe?

 We make sure that the data on our database is as secure as possible. The database is only accessible by approved colleagues with passwords, and is run by IT systems with very high standards of security. The physical notes that research nurses complete before transferring the information to the database are kept in locked rooms accessed only by hospital staff, or on hospitals’ secure electronic healthcare record system.

We make sure the data is as confidential as possible by using unique participant IDs rather than names. The data collected (including date of birth, NHS number, and postcode) is only accessible by members of the study team, and is not disclosed beyond this. We intend to retain the study data (including date of birth, NHS number, and postcode) indefinitely. We have undertaken to review this retention every 5 years with oversight from the Confidentiality Advisory Group of the UK Health Research Authority. 

It is possible that survivors of new diseases and exposures may go on to develop problems that we can’t imagine at present. It is impossible to understand the long-term health and social effects among survivors of new diseases or exposures unless studies are made of these survivors in the future. For example, we are now using the data from severe COVID survivors to understand “Long-COVID”. Having access to the NHS numbers allows researchers to understand health outcomes over many decades. This could be incredibly important particularly for children and the unborn children of pregnant women who are infected by new diseases or are potentially exposed to other harms of public health importance.

How can I opt out of having my data collected?

 If you have opted out of your data being used for research via the National Data Opt-Out (https://www.nhs.uk/your-nhs-data-matters/), we will remove your data from our database if you have been recruited.

If you have not opted out of your data being used for research via the National Data Opt-Out but you would like to opt out from your data being used for our study, you can contact the study team to request this at ccp@liverpool.ac.uk. If you want to opt out please send us an email including your name, date of birth, NHS number and postcode. You do not need to give a reason for why you want to opt out. We will look for your details in our data and if we find it we will delete it. In any case we will email back to you within 14 days to tell you if we found your data and if we did, to confirm that your data has been removed.

You can also telephone the study team to request that your data be removed by calling 07506 653560.

Data protection regulation provides you with control over your personal data and how it is used. Further information about your rights with respect to your personal data is available at https://compliance.admin.ox.ac.uk/individual-rights or by contacting the study team.  The University’s data protection officer can be reached at data.protection@admin.ox.ac.uk.

If you would like to learn more about our study and how patient data is collected, used and protected, please visit click here.

ISARIC CCP Patient Notification Form v0.2 5^th May 2022

Peritoneal Mesothelioma Retrospective Sample Collection

Sponsor:      Royal Papworth Hospital NHS Foundation Trust

Study Title:   Peritoneal Mesothelioma Retrospective Sample Collection

REC ID:         20/L0/1038

Peritoneal mesothelioma is a rare aggressive, subtype of mesothelioma and there is an unmet need within the research community for peritoneal mesothelioma clinical trials/research studies.

Royal Papworth Hospital NHS Foundation Trust is the sponsor for this study based in the United Kingdom and will act as the data controller for this study. This means that we are responsible for looking after the information and using it properly. To safeguard patient rights, we will use the minimum personally-identifiable information possible. Royal Papworth Hospital NHS Foundation Trust is legally required to keep identifiable information for 15 years after a research study has completed.

This study will use tissue originally collected for diagnostic purposes and information collected from medical records and organisations such as Public Health England (National Cancer Registration and Analysis Service) and NHS Digital. This type of information is regarded as a special category of information. It will help researchers to interpret the results of their studies using the tissue. 

Once tissue has been checked for suitability, a minimal data set will be sent to NCRAS, which has routinely collected cancer data for many years. If a match is found, NCRAS will return relevant information (anonymised) linked to that tissue sample. 

The medical information will only be used for the purpose of healthcare research and will not be combined with other information in a way that could identify a patient. All information released with tissue to researchers and their organisations will be fully anonymised and will only be used to conduct research in accordance with the UK Policy Framework for Health and Social Care Research. Organisations may be universities, NHS organisations or companies involved in healthcare research in this country or abroad.

More information about how patient data is used for research and planning in the NHS can be found here https://www.nhs.uk/your-nhs-data-matters/

You can find out more about how we are using information in this study by contacting the Chief Investigator Professor Stefan Marciniak at stefan.marciniak@nhs.net . If you have any concerns about your data potentially being included in this study you can contact stefan.marciniak@nhs.net .

Effective Treatments for Thoracic Aortic Aneurysms (ETTAA): A prospective cohort study

The aorta is the main artery that carries oxygen-rich blood from the heart to the body. The thoracic aorta is the section of the aorta that is in the chest.  An aortic aneurysm is a swelling or bulging at any point along the aorta. An aneurysm usually occurs where the wall has become weak and has lost its elastic properties, so it doesn’t return to its normal shape after the blood has passed through. [Further information about thoracic aortic aneurysms can be found here.]

As the aneurysm grows, the chance of the aortic wall tearing (called a dissection) or rupturing increases.  A rupture may never occur but if it does, it is fatal in about 80 per cent of cases. Therefore, once an aneurysm reaches a certain size, or if it appears to be growing quickly, doctors may recommend intervention in the form of either surgery or stenting.

For small aneurysms, experts recommended a period of Watchful Waiting, with regular monitoring, until the aneurysm had grown to about 6cm in diameter.  For patients unfit or unwilling to have surgery, Conservative Management is recommended along with medication and lifestyle changes.

There are currently two main methods of repair for arch/descending Thoracic Aortic Aneurysms: Open Surgical Repair (OSR) and Endovascular Stent Grafting (ESG).  ETTAA researchers conducted a systematic review of the published literature and found that there was limited and increasingly dated evidence available comparing ESG and OSR for treatment of arch/descending TAA [You can read the results of the systematic review here]. 

There was insufficient information to design a clinical trial comparing treatments for Thoracic Aortic Aneurysms so the ETTAA prospective cohort study was designed and conducted to investigate aneurysm growth rates, monitor patient outcomes and collect information regarding NHS costs. 

Between 2014 and 2019, ETTAA study teams from 30 NHS hospitals recruited and followed up 886 participants with a chronic thoracic aortic aneurysm (>4cm diameter).  Data was collected by local hospital research coordinators and collated by the core team at Papworth Trials Unit Collaboration.  Information was collected in order to observe aneurysm growth, record clinical treatments and measure patient outcomes including survival and health related quality of life. This observational study recruited 321 women and 565 men, average age 71 years. Most were being treated for high blood pressure. Stent Grafting was conducted in 150 patients, Open Surgery in 135 whilst 489 patients underwent Watchful Waiting and 112 Conservative Management.

The first ETTAA results paper has been published in the European Heart Journal.  To read this paper please click here.

A further publication can be viewed here.

Carol Freeman on behalf of Mr Stephen Large and the ETTAA Collaborative Group.

TIMES: A Randomised Mechanistic Study Comparing the Effects of Different Anti-platelet Combinations (Ticagrelor vs. Placebo/ Clopidogrel) with Aspirin in Patients presenting with STEMI Treated with Primary PCI

Ticagrelor is an antiplatelet medicine used to prevent blood clots. It is known to reduce red blood cell uptake of a chemical messenger in the body called adenosine, and researchers think that this process (i.e., more adenosine flowing free in the heart), may improve the flow of blood through the heart after a particular type of heart attack called an ST-elevation myocardial infarction (STEMI).

The TIMES study was a scientific study designed to investigate whether the very early beneficial effects of Ticagrelor in heart attack, may in fact be due to its effect on adenosine rather than only due to an antiplatelet effect.

The study was conducted at Royal Papworth Hospital and 62 patients were recruited. All patients were first given another antiplatelet medicine called Clopidogrel and then randomised to receive either active medication (Ticagrelor) or dummy medication (Placebo). 50% of people received active medication and 50% received placebo. Patients then underwent a procedure called a Percutaneous Coronary Intervention (PCI) which is standard of care for a heart attack. After the PCI procedure patients who had received Ticagrelor continued to receive this daily and patients who had received Placebo were prescribed Clopidogrel daily. Patients had blood sample collections and ECGs at various time-points throughout the study.

The trial was stopped early after first interim analysis. Blood adenosine levels were no different at either timepoint between the 2 groups of patients but there was a trend towards less clotting in the heart in the group of patients randomised to Ticagrelor. It was concluded that Ticagrelor significantly reduces clotting compared to Clopidogrel but as the blood adenosine levels and measures of blood flow through the heart were no different between the 2 groups of patients, this possibly indicates that early Ticagrelor benefits are not mediated by improving blood flow in the heart.

RITA-MI: Rituximab in patients with acute ST-elevation Myocardial Infarction: an experimental medicine safety study.

During, and after, treatment for a heart attack, the heart muscle can become very inflamed due to the ischaemia (lack of blood flow) and reperfusion (restoring blood flow). There is strong evidence to show that the inflammation is mediated by the immune system (blood cells that fight infection) and can lead to long lasting heart damage. The RITA MI trial, sponsored by Royal Papworth Hospital and run by the Clinical Trials Unit, was interested in temporarily decreasing this immune response with medication (RITUXIMAB) and preventing this inflammation. The immune system should completely revert back to normal after the medication is given. Although RITUXIMAB has been safely administered in people for disease like Rheumatoid Arthritis, it had not been used in heart disease. But recent research showed that it may be useful in treating inflammation and therefore preventing future heart failure after a heart attack.

24 patients were recruited to the trial in total. Four escalating doses of Rituximab (200, 500, 700, and 1000 mg) were used and there were 6 patients per group. The primary end point was safety of the drug, whilst the secondary end points were looking at changes in circulating immune cell subsets including B cells, and cardiac and inflammatory biomarkers. 

In this first RITA-MI trial, we have shown promising safety and feasibility data for the use of a single infusion of rituximab in patients with ST elevated myocardial infarction (STEMI). In addition, we provided important new insights into the feasibility and pharmacodynamics of rituximab and novel immunological insights have been gained into its effects in patients.  The data from this first trial has provided the pilot data for a successful EU grant application to conduct a multi-national randomised controlled trail using a single dose of Rituximab to assess efficacy, which will begin later this year.  Royal Papworth and the Clinical Trials Unit will act as UK sponsor representative for this trial and Dr Hoole will be the UK based Chief Investigator. 

Amaze (the adjunct maze trial)

A randomised controlled study to investigate the clinical and cost-effectiveness of adding an ablation device-based maze procedure as a routine adjunct to elective cardiac surgery for patients with pre-existing atrial fibrillation.

Why did we do this study?

The study looked into a method of treating atrial fibrillation (AF) to see how well it worked and if it would be good value for money for the NHS.

AF is a condition where the upper chambers of the heart (atria) beat unevenly due to abnormal electrical signals. As a result, the whole heartbeat is abnormal.  Some people with AF are not aware they have it, but others feel unwell and suffer palpitations (a feeling of the heart thumping in the chest which can be unpleasant). 

People with AF tend not to live as long as those without it as their hearts work less efficiently. They are also at greater risk of having a stroke.

Because of this, people with AF often take blood-thinning medicine (warfarin or similar) to reduce the risk of stroke, but these drugs are not without risks (they can cause bruising or bleeding). Taking warfarin can also be a nuisance because it needs regular clinic check-ups and blood tests.

The reason for this study was to see if treating the electrical abnormalities in AF would give people a longer and better quality of life and would cut down on the need to take drugs such as warfarin.

There is already a treatment for AF called the ‘maze procedure’. It can be done at the same time as a patient’s heart operation (hence the ‘adjunct maze’).   The surgeon uses an energy device to make a special pattern of lines (a bit like a maze) on the walls of the atria blocking the abnormal electrical signal to help the heart beat normally again.

Patients with AF who have the maze have a better chance of having a normal regular heartbeat (50% - 90%) after their heart operation than patients who don’t have the maze (5% - 10%). However, it wasn’t known if the maze would improve the things that matter to patients, for example, how long they would live for, their later quality of life and what drugs they might still have to take.

Because it wasn’t known if the adjunct maze would improve patients’ lives, we compared patients who have the adjunct maze procedure to those who had their heart operation without the maze.

Information we collected and how we hoped it would help?

About one month before heart surgery, patients attend a pre-admission clinic at the hospital.   They were shown how to record an electrocardiogram (ECG) at home.  This monitored and recorded their heartbeat over 4 days at home.

When patients came in for the operation, the research nurse asked questions about their health, how they are feeling and what drugs they are taking.

On the day of surgery, patients were randomised to have either their planned heart operation alone, or their planned heart operation with the adjunct maze procedure. 

After the operation all patients received the usual medical treatment as they recover from the operation. Before patients left hospital, the research nurse also completed a questionnaire with them to ask how they are feeling at that point.  These questions were asked again at 6 weeks, 6 months, 12 months, and 24 months after the operation.

At the 12-month and 24-month visits only, patients were asked to take the ECG recorder home again to record their heartbeat for 4 days as they did before their operation.

How many patients were recruited?  Where will the study take place?

352 patients were recruited across 12 cardiac surgical centres with 30 surgeons, who had at least 2 years’ experience of performing AF operations.

Apart from Royal Papworth, patients were recruited from the following hospitals: Brighton & Sussex, Coventry & Warwickshire, Glenfield, Royal Brompton, Sheffield, Guys & St. Thomas, Derriford, Wythenshawe, Bristol, Blackpool, and Newcastle.

What the main findings of the study?

The study showed the maze procedure was a safe procedure. It significantly increased the rate of return to a normal heart rhythm. This was with no increase the rate of death or complications, and no increase the need for a pacemaker. It also showed that a complete left atrial maze would probably be all that most patients need. 

It was, however, not found to be cost-effective and, after 2 years, survival and quality of life were not found to be significantly better than those who did not have the maze procedure.

Although there was no difference at two years, after 5 years there does seem to be a trend towards those having had the maze procedure having fewer strokes. 

Feedback sessions to those who took part in the study will be taking place in the future.