Trial Summary

The Bronchiolitis Endotracheal Surfactant Study (BESS)

A phase-2 blinded randomised air-placebo-controlled trial of endotracheal surfactant (poractant alfa) in critically ill infants with bronchiolitis.

The Bronchiolitis Endotracheal Surfactant Study (BESS) is a national multi-centre randomised controlled trial to determine the efficacy and safety of endotracheal surfactant in reducing total duration of Mechanical Ventilation by 18 hours or more versus air placebo in the treatment of critically ill infants with bronchiolitis. The trial is led by Calum Semple, Consultant in Paediatric Respiratory Medicine, Alder Hey Children's NHS Foundation Trust and Professor of Child Health and Outbreak Medicine, University of Liverpool.

Patient Information Sheets
BESS Parent PISC
What is BESS and why are we doing this research study?

Bronchiolitis is a winter viral chest infection that causes breathing difficulties in babies. There is no vaccine and no specific treatment for Bronchiolitis. Babies with Bronchiolitis may need intensive care where they can be given help with their breathing from a Mechanical Ventilator.

BESS is a study looking at whether a liquid called surfactant could help babies with Bronchiolitis to reduce the time they need to be on the Mechanical Ventilator. Surfactant has been used in premature babies with other lung problems for over 30 years, but we don't know if it will work in babies with Bronchiolitis.

Surfactant is a liquid made in healthy lungs that helps the lungs to inflate more easily. When a baby has Bronchiolitis, their lungs don't make as much surfactant as they normally do. The surfactant we are using in BESS is called 'poractant alfa' also known by the brand name 'CUROSURF®'. CUROSURF® has a European Marketing Authorisation and is licensed in the UK for use in babies with some breathing conditions, but not currently bronchiolitis.

We would like 284 babies age 6 months and under to take part in BESS. If your baby was born prematurely and has a corrected age of under 6 months, then they can still take part in BESS.

The results from BESS will help doctors and nurses treating babies with Bronchiolitis to know whether or not they should use surfactant in the future.

What is being tested?

The medicine that is being tested is 'Surfactant'. Surfactant is a liquid containing fats and proteins made in healthy lungs that helps the lungs to inflate easily. This medicine is currently used for the treatment of Respiratory Distress Syndrome in newborn babies.

The surfactant we are using in BESS is called 'poractant alfa'. It is extracted and purified from pig lungs (a 'porcine derivative' medicine). Many medicines come from animals. Religious authorities have long established views on the use of such medicines. The following religious authorities have reviewed BESS and given their opinion on this study:

For Muslim parents: The Research & Documentation Committee of The Muslim Council of Great Britain have advised that there is provision under Sharia Law for Muslims to use porcine derivatives in severe and life-threatening situations.

For Jewish parents: The Kashrus & Medicine Information Service of the United Synagogue and the Union of Orthodox Hebrew Congregations have confirmed that as surfactant avoids the mouth and is delivered directly into the lungs through a breathing tube, it is deemed acceptable (halochoh). Furthermore, Jewish dietary laws are suspended where life is threatened, so there is mitigation were some surfactant to find its way into the mouth. Also, there is scope for leniency as the surfactant has been chemically treated by the purification and extraction processes meaning it is no longer animal flesh.

Why my baby?

If your baby has been diagnosed with Bronchiolitis and may need intensive care where they can be given help with their breathing from a Mechanical Ventilator, you might be asked about taking part in BESS.

We would like 284 babies age 6 months and under to take part in BESS. The results from BESS will help doctors and nurses treating babies with Bronchiolitis to know whether or not they should use surfactant in the future.

Do I have to say yes?

No, you can decide that your baby should not take part in this research. If you do decide now that your baby will take part, you can also change your mind in the future and decide that they should stop taking part.

Either way, the standard of care your baby receives now or in the future will be the same whatever you decide.

What will happen if I take part?

If you agree to your baby taking part in BESS, they will be given surfactant or air (the dummy or 'placebo') up to three times over 24 hours. If your baby gets better quickly they might only need to be given the study treatment one or two times.

A Respiratory Physiotherapist is a specialist who helps looks after babies and children with breathing problems. Before giving surfactant or air, a Respiratory Physiotherapist will suck out any thick secretions (mucus) in your baby's airway (breathing tubes) by flushing them with safe salty water (saline). This is called Bronchoalveolar Lavage (BAL) and sometimes called respiratory toilet. BAL helps stop sticky mucus in your baby's airway from causing a blockage. Performing a BAL does not hurt your baby and is often part of normal care. Babies with bronchiolitis are likely to have several BALs even if they don't take part in BESS, because this disease causes thick sticky secretions in the airways and these need to be removed to help your baby to breathe.

In BESS, we need to do a BAL before giving the surfactant or air to make it safer. This also gives us an opportunity to keep some of the sticky mucus that has been sucked out from your baby's lungs. We will use this mucus in our research, to look for signs of infection and inflammation in the lungs. If we were not doing research, then this mucus would not be used and would be thrown away.

Babies on PICU have very small blood samples taken each day to check how much breathing support they need from the Mechanical Ventilator. We call these “Blood Gas” samples because we use them to look at the amount of oxygen and other gases in their blood. These samples are about 2 drops of blood and are usually taken from a “line” or a heel prick. We need to know the Blood Gas results before and after we give each study treatment to understand if the treatment is working. If your baby takes part in BESS, then they will have 3 more Blood Gas samples in the first two days of the study than they would if they didn't take part. To avoid disturbing your baby, we won't do a Blood Gas if your baby has recently had one done as part of their usual care.

We will collect information about your baby's time and treatment in hospital to understand whether or not the surfactant helps babies with Bronchiolitis to breathe on their own and recover more quickly.

We will send you a questionnaire by email at 6 months and 12 months after your baby takes part in BESS, to ask how they have been getting on with their breathing. If you do not have an email address, we can send you a paper copy. These questionnaires take around 10 minutes each to complete.

We would also like to know if you would take part in our Parent Experience study. This involves a questionnaire and/or telephone interview in around 2 months' time. An experienced researcher will ask you about the consent process for BESS and what it was like to take part in this study.

Are there any risks to taking part?

If your baby receives surfactant, a potential benefit of this treatment might be a reduced period of time spent on the Mechanical Ventilator, which could reduce the risk of complications associated with being on the Mechanical Ventilator and in intensive care.

Before surfactant or air is given, your baby will have a BAL to reduce the risk of thick secretions blocking the tube into your baby's lungs. Even with the BAL, there are some temporary side effects that often occur in the first few minutes after the BAL or surfactant is given: a slowed heart rate ('bradycardia'), low blood pressure ('hypotension'), or a drop in blood oxygen level ('desaturation'). These problems are commonly seen in babies in intensive care with Bronchiolitis just because they are so unwell. The hospital team caring for your baby will look out for these problems and will make sure your baby gets extra support if needed.

Are there any benefits of taking part?

We cannot promise the study will help your baby but Surfactant has been used in preterm babies for over 30 years and is a safe treatment for breathing problems caused by prematurity. There is some information suggesting that surfactant might help babies with Bronchiolitis but not enough evidence to give doctors confidence that it should be used routinely. Some doctors do use surfactant when treating babies in intensive care with Bronchiolitis, but others don't. We don't know how well surfactant works in these babies, which is why we are doing this study.

What is the Parent Experience Study?

Your views and experiences of taking part in BESS are very important to us. Whether or not you agree to your baby taking part, we wish to learn from your experiences of BESS and being asked to take part while your baby is unwell. We have called this the Parent Experience study. You do not need to agree to take part in BESS to provide your views for the Parent Experience study. If you do not want to take part in the Parent Experience study this will not affect your care or affect your participation in BESS.

In the Parent Experience study, we will ask if you would like to complete a brief questionnaire about your experiences of BESS. A researcher from the University of Liverpool would also like to talk to some parents by telephone. These discussions will last about 40 minutes and will include how you felt about the BESS consent process, why you did or did not provide consent and how you think consent should be sought for similar situations in future. This study will inform how we ask other parents about BESS and future children's intensive care research. If you take part in an interview you will be sent an Amazon voucher to thank you for your time.

Randomised patients
131
Target patients
284
Open sites
15
Target Sites
15
Study funder

This study has been funded by the National Institute for Health Research's Efficacy and Mechanism Evaluation (EME) Programme (ref: 12/205/28).

NIHR EME Programme NIHR EME Programme
Study Sponsor

The University Of Liverpool

Study review and approval

The study has been reviewed by a research ethics committee, who have agreed the study is being conducted in a correct and appropriate manner. The study has also been approved by the Medicines & Healthcare products Regulatory Agency (MHRA).

Collaborators



Participating Sites

Who is doing this research?

The study is being run in a number of hospitals around the UK, and is being organised by University of Liverpool, University of Southampton and University of Leeds.

BESS will run at 14 hospitals across the UK over 3 winters. This map shows where BESS will be open in Season 1 (Winter 2018/19).

View BESS Season 1 Sites in a full screen map

Professor Calum Semple
Image of Prof. Semple

"Like many children's doctors I'm frustrated that we have no specific therapy for bronchiolitis. This nasty disease has been in my sights since I joined Liverpool as a National Clinician Scientist in 2002. Since then we've learnt a lot about this disease but only now do we have an opportunity to trial a treatment for babies with the most severe form of this disease.

My research career started at the Middlesex Hospital Medical School with my BSc project being supervised by Professor Richard Tedder. I moved with Richard to UCL where I submitted my PhD Thesis A culture independent method for the measurement of cell-free HIV-1. I completed my medical studies at the University of Oxford.

I was appointed Senior Clinical Lecturer in Child Health at University of Liverpool by the Vice Chancellor's Award in 2006 and promoted to Professor of Child Health and Outbreak Medicine in 2017.

I and my research team were each awarded the Queen's Ebola Medal for Service in West Africa for our research activity in Sierra Leone in 2014-2016."

Professor Semple was a co-investigator on FLU-CIN (2009-12) and MOSAIC (2010-2014), studies that characterised the clinical features and immunological response to the Influenza pandemic infection.

He is chief investigator for BESS (2018-) FLU-CATs (2013-), ISARIC-WHO Biological Sampling Protocol (2014-) and co-investigator on ARCHIE (2014-), all NIHR portfolio studies that study Severe Acute Respiratory Infection. He was Consortium Lead Investigator for the Ebola Convalescent Plasma study in Sierra Leone (Ebola_CP) and Co-Investigator on the sister study in Guinea (Ebola_Tx).

He is an Honorary Consultant Senior Clinical Advisor to the Chief Medical Officer and Cabinet Office of the UK Government for Clinical Countermeasures and sat on the Pandemic Influenza Clinical Operational sub-group advising these offices. He is a member of the New and Emerging Respiratory Virus Threats Advisory Group (HMG UK), WHO Scientific Technical Advisory Committee on Ebola (WHO STAC Ebola) and is Senior Clinical Editor of Influenza and Other Respiratory Viruses.

Professor Semple provides a tertiary paediatric respiratory outpatient clinic and runs the regional paediatric bronchoscopy service with Prof Kevin Southern at Alder Hey Children's Hospital for the North West region of England.

Contact

If you are a parent of a baby taking part in BESS we advise you to speak to your baby's care or research team at the hospital where they joined BESS.

If you have any questions about BESS please contact bess@liverpool.ac.uk

Chief Investigator – Prof Calum Semple
Please contact me for any clinical queries, co-enrolment requests, safety concerns or site expressions of interest in participating.
+44 (0)151 252 5440
M.g.semple@liverpool.ac.uk
Project Manager – Blessing Osaghae
Please contact me for finance queries, communications and questions relating to the Parent Experience study or BAL sampling.
+44 (0)151 228 4811, ext. 3956
B.osaghae@liverpool.ac.uk
Trial Manager – Chloe Donohue
Please contact me for all queries relating to the trial, making safety reports, IMP and randomisation issues or requests for support at site.
+44 (0)151 795 8757
bess@liverpool.ac.uk