My PRONTO Journey – World Sepsis Day 2024

-Blog by Julie Carman

As World Sepsis day comes round again, I invite you to join me as I share my thoughts and observations as the Patient and Public Involvement (PPI) representative on working with the PRONTO trial research team.

The PRONTO Trial

PRONTO (PROcalcitonin and NEWS2 evaluation for Timely identification of sepsis and Optimal use of antibiotics in the Emergency Department).

My name is Julie and I have lived experience of sepsis. I am and have been a volunteer with UK Sepsis Trust for many years providing peer support online and at face-to-face UK Sepsis Trust Support Groups. This film explains my story and this blog highlights how I am using my lived experience to help improve patient health outcomes.

As a sepsis survivor I have seen first-hand how important prompt treatment with intravenous (IV) antibiotics is once sepsis is confirmed. As a volunteer with the UK Sepsis Trust facilitating Support Groups and providing peer support to others, I am aware of the side effects of powerful lifesaving antibiotics and the ongoing issues they can cause, including hearing loss and gastric problems.

The PRONTO trial aims to ensure that timely antibiotics are given appropriately, but not unnecessarily, leading to improved outcomes whilst playing an important part in reducing antibiotic resistance. 

The journey begins

I was first approached at a workshop to which patients and public were invited in August 2018. We discussed antibiotic resistance and its causes and why it would be beneficial to try and reduce antibiotic resistance. Explanations were given as to what is a biomarker, deferred consent, randomisation, how patients with suspected sepsis present to hospital, and how it was hoped that an additional blood test called Procalcitonin (PCT) would change current practice. It was explained that this would be a non-inferiority trial – to determine whether this new (additional) intervention is not inferior to another (established) intervention.

We were asked to consider what outcomes were important to us as patients, our concerns, and how and when we felt patients would prefer to be contacted as the trial progressed.

Some quotes from the day:

“It’s another diagnostic tool – why would you not use it?”

“It could help patients, reduce cost of hospital care and reduce cost of antibiotics.”

“Would we be pioneering? Can we trust it?”

“How does the test differ from C-Reactive Protein (CRP)/other biomarkers?”

“Maybe if I’d had test earlier on it may have changed my outcome?”

We were given reassurance that if early interim analyses picked up harmful effects the trial would be stopped.

After expressing my interest, I was invited to be the PPI representative for the PRONTO trial and our first Trial Management Group (TMG) kick-off meeting with the whole team was held in Liverpool in September 2019. The PRONTO journey had begun!

What we already know

Sepsis is a serious condition and is not always preventable. Currently, approximately 30% of patients who are diagnosed with severe sepsis die (approx 48,000 deaths per year in the UK). Sepsis is difficult to diagnose as it mimics other illnesses. Once diagnosed rapid treatment is crucial to survival and antibiotics are the first line treatment. PCT is a useful biological marker for assessing severity of infection and a PCT measurement from the patient, along with the routinely used NEWS2 score (a set of physiological measurements) could help clinicians in their diagnosis.

Overuse of antibiotics is leading to Antimicrobial Resistance (AMR) – which means the antibiotics we have currently may not treat future infections and illnesses. AMR is a threat to both the NHS and patients worldwide. A system wide approach to the judicious use of antibiotics is needed to preserve future effectiveness.

What we needed to know and why

The problem of AMR is not just relevant to the UK – it is global! Some of the questions we needed to ask to change current standard practice in the UK were:

• Is there a safe way that fewer patients can be given antibiotics that will not cause patient harm?
• Is there a test that could be used in the Emergency Department that could help clinicians safely make this decision/contribute to their decision making?
• Would such a test be easy to use by staff in a busy Emergency Department and are the results reliable?

How could we find out?

The PRONTO trial had two arms. One set of patients received standard sepsis care, and the other set was given PCT test at the bedside and then treated according to the results of this test. The results were collated and compared to ascertain any difference in mortality. Clinicians could override results of the test and treat according to their clinical judgement at any point, if required.

Some of my tasks as the journey progressed

I attended Trial Management Meetings monthly from December 2019 until the end of the trial, initially face to face but most often on TEAMS or Zoom as the COVID pandemic hit. I prepared posters for display in A & E departments so patients and relatives were aware they or their loved ones may be involved in a trial. I developed a sign posting leaflet to go in patient discharge packs with links to the UK Sepsis Trust and bereavement services.

I contributed to a patient information sheet in an easy to read and understand format, explaining why the hospital was taking part, why the trial was being done and what it hoped to achieve. This included information on how long participants would be involved in the trial and the reason for the 28 day and 90 days follow up interviews. It also included information on how their data would be kept confidential and who had responsibility for the data. There was an option to withdraw from the trial at any point if they so wished and a named person and contact number to contact for further information.

I advised on the wording and the appropriate tone for letters to be sent to patients relatives following a death, and contributed to the questions and format for the 28 day and 90 day interviews with patients and the interviews with Health Care Professionals (HCPs) involved in the trial.

I was able to use my contacts from my UK Sepsis Support groups to comment on documents to ensure we had included a broad patient perspective.

What were the challenges and complexities as the journey continued?

Within a few weeks of the PRONTO trial being approved, the COVID–19 pandemic arrived, and face-to-face meeting plans had to be changed to Zoom or TEAMS. COVID-19 meant the Acute teams were under extreme pressure during and post pandemic, whilst also being asked to recruit patients to the PRONTO trial.

There were some issues with the PCT tests as the company who made the tests were unable to supply reagents for a number of weeks, leading to delays in recruiting patients. As the trial progressed the company discontinued production of the tests leading to further delays and challenges for the PRONTO team. A new supplier was found to allow the trial to continue, and we needed to apply for funding extensions to account for this and thankfully this was granted. Our A & E teams and Research nurses had to learn to use a new test in an already very stressful environment.

What were the successes?

As PRONTO was conducted in an emergency department, the trial used a deferred consent model, meaning that patients were enrolled into the trial before discussions on the research could be held and consent taken. This was to ensure that no delays occurred in receiving urgent medical treatment. However, despite this patients and their relatives were keen to be enrolled and stay involved overall. Despite the many challenges of COVID-19, including the overwhelming workload in busy Accident and Emergency departments, the health professionals at most of the sites continued to recruit patients and support the PRONTO trial throughout.

A slight diversion on our journey

The PRONTO trial had ethical approval to use the deferred consent model (often patients are too unwell to have a discussion around whether they wish to take part in the trial on admission to hospital.) As time progressed this led some members of the trial team to develop a further piece of work exploring whether bereaved families wish to be informed that their loved ones had participated in a trial before they died, and if so, when and how they would wish to be informed.

The ENHANCE study team interviewed family members whose loved ones had died in the last three years following an admission to emergency or critical care. We also held a workshop with patient’s relatives, Medical Examiners, bereavement teams and research nurses to obtain their views on whether and how this should be done. This will, in the future, inform other trials and ensure the views of patients loved ones are listened to, understood and acted upon.

The journey’s end or is it just the beginning….

We now eagerly await the final results to see whether or not there were fewer deaths in the PCT arm compared to the standard care arm. If so, will these numbers be significant, and will this lead to a change in practice of the current standard of care? Only time will tell as we wait in anticipation as the study statisticians analyse the data.

The results of the PRONTO trial and public dissemination of the results are expected to be released in the Autumn of this year.

– Blog by Julie Carman PPI Representative PRONTO Trial August 2024

The PRONTO trial was funded by the National Institute of Health and Care Research (NIHR), sponsored by University of Liverpool and centrally co-ordinated by the Centre for Trials Research, Cardiff University.