Spiral came on board as the software partner of choice for the TAME trial over five years ago.
Since then, we've supported the team to take their multicentre randomised control trial to 63 sites in 17 countries. We speak with Dr Glenn Eastwood, TAME Chief Principal Investigator, about the study and how Spiral has enabled them to produce a database they can be confident in. Alongside TAME, Dr Eastwood is a Senior Research Fellow at the Australia New Zealand Intensive Care Research Centre within Monash University.
The TAME trial study compares the targeting of normal arterial carbon dioxide levels to slightly higher than normal carbon dioxide levels for 24 hours in patients admitted to the ICU following cardiac arrest in the community. The research seeks to discover if leveraging off the neuroprotective anti-inflammatory and increasing blood flow effects of having slightly higher carbon dioxide levels in the blood improves the neurological outcome of patients who survive to six months.
Design thinking that embeds multiple comparative data.
Spiral's software has allowed him to have confidence in the quality of the wealth of information collected in the TAME trial, as the layout and structure of the software makes it so user-friendly.
"As a Research Manager and Coordinator at Austin Hospital, I had been a user of the Spiral data management system for previous trials and felt supported by their team. I was impressed with its user-friendliness and good layout, so when it came time for me to choose a trial platform for TAME to run on, I immediately put forward Spiral. I was confident they could expand into other countries with us."
This study was also unique because it was a harmonised trial embedded in a two by two factorial design. Under serendipitous timing, the TTM2 trials were looking for funding simultaneously as us but were looking at temperature management for patients after cardiac arrest. By embedding one trial database and one case report form, the Spiral platform allows sites to do one or both trials, allowing both trials better access and site leverage.
The final participants were recruited in September 2021, and their 6-month follow-ups with trial participants were completed in February, aligned with their initial projections of completion all those years ago.
Whilst the pandemic could have been a spanner in the works, as different countries came on board at various stages, certain sites could enrol patients when others were not, and vice versa. Now, the team are focused on getting all their data into Spinnaker, and we eagerly await the study's findings, which are expected to be released later this year.
Ensuring that each of the 65 sites taking part in the trial had a good user experience was essential to this study. Dr Eastwood acknowledges this is one of Spiral's greatest strengths, with the software applying common sense with logical and chronological tabs and inputs.
He also notes that the design's attention to detail provided exceptional ease of use, as he could source the correct information quickly and accurately.
"The database field has a prefix that corresponds with the case report form, and that abbreviation is so important for investigators because I want easy access to that variable on that particular row of that table in a paper. Details like that were a blessing."
This attention to detail extends further, allowing for the use of different units of measurement. Some sites this trial was running at used millimetres of mercury as a unit of measure, and others used kilopascals. Ensuring that clinicians were able to input their data in a way that made sense to them meant that the users didn't have to do more calculations than necessary, and the database took care of the rest.
"No matter where you were, you're able to tailor the data coming into the database to suit the site."
Dr Eastwood acknowledges the ease of working with the Spiral team, which allows him to focus on his area of expertise. Not only has he found the software reliable and built for purpose, but the simple contract for build and clear monthly maintenance fee have been helpful and reassuring when budgeting research funding.
This research has been ten years in the making, and it's easy to see that Dr Eastwood's motivation is human compassion. He sees his role as nudging care, little by little, to make improvements in patient outcomes and wants people to be able to hug their kids and enjoy a new part of their life that they might not get otherwise.
He acknowledges that the Spinnaker database allows them to record information to make it easy to turn it into clinical language for their clinicians. This is one of the ways that this study has had participation across so many sites with ease.
Moving into the future, data security and data protection are amongst the top priorities of policymakers, particularly in the countries where TAME has operated. Dr Eastwood is grateful for Audrey and the Spiral team's assistance in answering the questions about the Spiral software, with a clear understanding of the ins and outs of their data processes and policy adherence. He acknowledges that systems like Spiral's that are clear on these requirements will become more important as the research community continues to evolve in a connected world.
"Spiral provides a monthly update about the security, the firewall and the system had rarely had any downtime which was reassuring as the trial all around the world and the clinicians taking part needed access around the clock."
"Products that help facilitate clinical research, like Spinnaker, are just going to get more and more important because there's so much data out there and so much opportunity to bring this data together to help create better patient outcomes. I've seen Spiral's flexibility and adaptability and am excited to see how they evolve."
Thousands more vulnerable people in England are now eligible to receive the UK’s second oral antiviral treatment for COVID-19. Paxlovid reduced the risk of hospitalisation or death by 88% in clinical trials and is already available directly through the NHS to highest-risk patients. The UK has procured more antivirals per head than any other country in Europe with over 4.98 million courses ordered so far.
The PANORAMIC national study is the UK’s fastest-ever recruiting clinical trial of its kind, run by the University of Oxford in close collaboration with GP hubs. It is already available directly through the NHS to those whose immune systems mean they are at higher risk of serious illness who test positive for the virus – including those who are immunocompromised, cancer patients or those with Down’s syndrome.
The PANORAMIC study makes antivirals available to a large number of patients while collecting further data on how the antivirals work where the majority of the adult population is vaccinated. It ensures antivirals are being used in the most effective way and is crucial in ensuring clinicians have the full information to prescribe antiviral treatments to patients in future
‘The addition of Paxlovid to the ground-breaking PANORAMIC study is an important milestone and will help us understand who benefits most from these treatments.’ - UK Health and Social Care Secretary Sajid Javid
While vaccines remain the most important first line of defence, antivirals target the virus at an early stage, preventing progression to more severe, or even critical, symptoms.
The UK government has secured 2.75 million courses of Paxlovid (PF-07321332 and ritonavir), made by Pfizer. Those who enrol in the PANORAMIC study will be randomly allocated to receive either an antiviral treatment in addition to standard NHS care, or standard NHS care only.
As a study in our manifest, Spiral has now added Paxlovid to the PANORAMIC Trial platform. For Spiral and the team, this means lots of coding and extensions to the database to get everything ready for randomising. We’re so excited to see the growth in this study! Watch this space as we bring you more news on this aspect of the trial as it develops!
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Looking back on the trial and the COVID-19 climate which we still find ourselves in, it’s incredible to see how quickly things happened. On the 10th of March 2020, the first patient was enrolled at Royal Melbourne Hospital, with the second following on the 13th of March. On the 17th we saw another 4 patients enrol before the floodgates opened.
Now two years on since the first enrolment, we have watched as the total number of patients has climbed to an astounding 11,032 with almost 20,000 randomisations. 17,581 of these were with suspected or proven Covid-19. There are now 357 active sites across the globe working within this trial and 55 current or completed interventions in 16 domains.
Therapeutic-dose anticoagulation with heparin has shown to increase the probability of survival for those hospitalised as non-critically ill patients with Covid-19. We’ve also learnt how full-dose blood thinners benefit moderately ill COVID-19 patients and have seen how tocilizumab and sarilumab are equally effective for the treatment of patients with severe COVID-19 - the most effective interventions included in this particular domain.
Before Covid-19 first made itself known, the world of clinical trials was at a remarkably different place. The challenges that existed then are still present now, but the global pandemic has highlighted just how easily health risks can cross borders. We’ve also witnessed the speed at which things can change, demonstrating a need for global cooperation and unity within the medical community. This pandemic has mobilised researchers worldwide on a scale and timeframe that has never before been witnessed for one disease.
The immense pressure that has been placed upon researchers, regulators, trial technicians, doctors and nurses (the list goes on) has been undeniable. We’ve seen how important well-designed randomised clinical trials are for both patients and medical staff as well as a need to move quickly in a time of incredible uncertainty.
Spiral has been involved in the REMAP-CAP clinical trial for the past two years. We have dedicated several members of staff to developing and delivering the software needed to perform this study within our Spinnaker platform. Being highly adaptable and flexible in this current global environment has been a crucial aspect for our team, ensuring that we deliver exactly what is needed to those working on the frontline, making trials like REMAP-CAP faster, easier and smarter.
To put it simply, worldwide, REMAP-CAP has been one of the most important critical care trials of the pandemic, one that Spiral continues to be proud to be a part of.
‘It’s an absolute privilege to be working on this project with the global REMAP-CAP family. The past two years have been crazy - although we were preparing the platform for a pandemic nothing prepared us for the global nature of this pandemic, the speed of its spread or how often the disease adapted. The dedication of the team at Spiral to meet these challenges has been astounding’ - Audrey Shearer, Spiral Founder and CEO
“We want to thank every single one of the 10,000 people who have taken part in the PANORAMIC trial to date. Your vital contribution to this remarkable study will provide key evidence in record time for a potentially game-changing class of new COVID-19 treatments.”
Over ten thousand participants from right across the UK have now taken part in the NIHR-funded and supported PANORAMIC trial - the world’s largest study into new antiviral treatments against COVID-19 in community, ambulatory care.
This trial was recently launched in December last year but only took a few months to reach this milestone. It is also believed to be the world’s largest study of community-based treatments for acute COVID-19, in addition to the UK’s fastest ever recruiting interventional trial delivered through primary care.
Our Spiral software is helping the trial to rapidly generate evidence on which of the people suffering with COVID-19 at home and in the community are helped the most by the new antiviral treatments. All without needing to be treated in hospital.
More in depth information on the Panoramic trial and its progress can be found here via NIHR.
The aim of PLUS was to conduct a multi-centre, blinded, randomised, controlled trial (RCT) to determine whether fluid resuscitation and therapy with a "balanced" crystalloid solution (Plasma-Lyte 148®) decreases 90-day mortality in critically ill patients requiring fluid resuscitation when compared with the same treatment using 0.9% sodium chloride (saline).
The newly published results have determined that intravenous fluids used in intensive care such as the commonly used saline is as effective at keeping people alive and their organs functioning as more expensive ‘balanced’ solutions.
The results not only provide doctors with greater certainty about the safety and benefits of saline solution but also have broader implications for treatment availability and costs around the world.
“Just about every patient admitted to the Intensive Care Unit (ICU) will receive intravenous fluids for resuscitation or as part of standard treatment,” said Professor Simon Finfer AO, an ICU physician and senior researcher at The George Institute.
“However, the best choice of fluid has been a longstanding issue of debate as some fluids were approved and licensed for use based on trials in small numbers of patients looking only at short term outcomes.”
Reports of intravenous solutions being used to treat critically ill patients date back almost 200 years ago. However, due to a lack of robust data, controversy over the choice of intravenous fluids has continued in the medical industry. The question has remained: In critically ill adults, does the use of balanced crystalloid solutions compared with saline reduce mortality and/or the occurrence of acute kidney injury?
To determine this, researchers at The George Institue for Global Health designed a clinical trial with the team at Spiral - the Plasma-Lyte 148® versUs Saline (PLUS) study - which involved over 5,000 patients across 53 sites in Australia and New Zealand.
They recruited adult patients admitted to participating ICUs during the study period who needed intravenous fluid resuscitation for their underlying medical condition. The patients were followed for a period of 90 days after treatment as previous research had shown around one in four would be at risk of dying within this timeframe.
The research team primarily looked at rates of death in patients who were given the BMES or saline while they were in the ICU. At 90 days after the treatment, the same number of patients in the BMES and saline groups had died.
The number of days that the patients required mechanical ventilation, kidney dialysis, their survival time in the ICU and in hospital, as well as major measures of healthcare costs were similar between the groups.
“We found no evidence that using a balanced multi-electrolyte solution in the ICU, compared to saline, reduced risk of death or acute kidney injury in critically ill adults,” said Prof Finfer.
These results have far-reaching implications for the medical industry. Each year in Australia 160,000 people are admitted to ICU. It is one of the most expensive aspects of healthcare with one day in ICU costing a minimum of $4,000. With high demand for ICU beds, resources and expertise, even a small difference in outcomes may result in important clinical and economic effects at the population level.
Spiral is proud to be a part of this study, making a tangible contribution to the medical industry, its professionals and patients.
Dive deeper:
The George Institute for Global Health
The New England Journal of Medicine
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