#CCR20: Major Clinical Trial Results in Critical Care Medicine to be Unveiled at Leading UK Conference

Results of three major critical care trials, and a fourth major international epidemiological sepsis study, to be unveiled at an international conference in Northern Ireland 

Critical Care Reviews, a not-for-profit, critical care project promoting open access to scientific advancement, today announced that three ground-breaking clinical trial results, and a major international epidemiological sepsis study, will be presented at the Critical Care Reviews Meeting 2020 (#CCR20), January 16-17, 2020 in Belfast, Northern Ireland.  

These presentations will provide a compelling focus for the two-day gathering of the global scientific community working within the area of critical care. Given the scientific significance of these results, their presentations will be freely live streamed globally and timed to simultaneous publication in major international medical journals. 

Data from the phase 2 VITAMINS trial, led by Dr. Tomoko Fujii (Melbourne, Australia), will be unveiled, reporting whether combination therapy of vitamin C, thiamine and hydrocortisone in patients with septic shock increases duration of time alive and free of vasopressor administration, compared with hydrocortisone therapy alone.i   

Globally, 50 million sepsis patients are treated in hospitals each year,ii with sepsis mortality rates in middle and low income countries reported to be as high as 60%.iii-v In addition, patients with sepsis have numerous short and long term complications and are at increased risk of death for up to several years following the acute event.vi-ix 

Experimental researchx to date has shown that intravenous vitamin C, together with corticosteroids and thiamine, are effective in preventing progressive organ dysfunction, including acute kidney injury, and in reducing the mortality of patients with severe sepsis and septic shock. However, clinical data in this area has been based upon a retrospective comparator trial and more robust data is required to determine efficacy. 

VITAMINS is the first multi-centre, open-label, prospective, phase 2 randomised clinical trial to yield robust scientific data in this area.i Pending the results of further trials, the outcome of the VITAMINS trial could have the potential to provide a new first-line treatment to patients with septic shock to improve mortality and patient outcomes. 

Pivotal phase 3 data from PEPTIC, the largest trial ever undertaken in the field of intensive care medicine, will also be presented at the annual gathering of critical care specialists. Led by Dr. Paul Young (Auckland, New Zealand), the trial will determine the effect on in-hospital mortality of implementing the use of a proton pump inhibitor (PPI) as the preferred agent for stress ulcer prophylaxis in mechanically ventilated adults in the intensive care unit (ICU) versus the use of a histamine-2 receptor blocker (H2RB).xi  

Stress ulcer prophylaxis is prescribed to more than 70% of adults who are acutely admitted to an ICU,xii with first line treatment recommended as either PPI or H2RB to prevent upper gastrointestinal 

 (GI) bleeding, which occurs in 2.6% of ICU patients in contemporary clinical practice.xii Whilst stress ulcer prophylaxis is administered to millions of ICU patients around the world every year, it is uncertain which type of ulcer prophylaxis is preferable. 

A systematic review and meta-analysis of the two treatment options has shown that use of PPI was associated with a significantly lower risk of overt bleeding than H2RB use,xiii however, it has also shown to be associated with an increase in developing nosocomial pneumoniaxiv-xvi and Clostridium difficile infection.xiv  

PEPTIC is the first registry-embedded cluster crossover trial ever undertaken and will provide important data regarding the comparative effectiveness of two commonly used approaches to stress ulcer prophylaxis in mechanically ventilated adults in ICUs.xi 

The 65 Trial, led by Professor Francois Lamontagne (Sherbrooke, Canada) and Mr Paul Mouncey (London, England), will evaluate the clinical and cost-effectiveness of permissive hypotension {mean arterial blood pressure (MAP) target range 60-65 mmHg whilst receiving vasopressors} in critically ill patients aged 65 years or over with vasodilatory hypotension, when compared with usual care.xvii  

Hypotension is common in critically ill patients, especially those with severe infections, and raising blood pressure is a complex process involving vasopressors and optimisation of intravenous fluid administration. Current clinical guidelines recommend maintaining MAP above 65 mmHg, xviii however, these guidelines are based on limited evidence and recent data suggests that targeting higher MAP values (between 75-85 mmHg) may be associated with an increased risk of death in older, critically ill patients.xix-xxi 

65 is the first trial to test the hypothesis that the benefits associated with permissive hypotension in older patients will outweigh the risks associated with lower MAP values and medical interventions to raise blood pressure.xvii 

The highly anticipated trial results will be presented by a panel of world-leading clinical experts at the Critical Care Reviews Meeting 2020, taking place at Titanic Belfast in Belfast, Northern Ireland.  

The IHME Sepsis Study, to be presented by Dr Kristina Rudd (Pittsburgh, USA), will, for the first time, report the global burden of sepsis. Sepsis is recognised as a major public health challenge, but until now detailed data on its extent has remained elusive. Global estimates for sepsis incidence, approximated at 50 million cases annually,ii and mortality, possibly as high as 60% in low and middle income countries,iii-v have historically extrapolated data from high-income countries internationally, raising concerns that such methods limit the burden of the condition in lower income countries, where the bulk of disease prevalence and severity lies. The true magnitude of this condition may be vastly higher. 

The IHME Sepsis Study, led by University of Washington and University of Pittsburgh School of Medicine physician-scientists, provides landmark estimates of global, regional, and national sepsis incidence and mortality, and is the first to estimate sepsis burden according to underlying cause, allowing for crucial insights into potential areas of focus to address this massive global health burden.  

Critical Care Reviews Founder, Dr. Rob Mac Sweeney, said; 

 “Now in its 8th year, the Critical Care Reviews Meeting has grown to establish itself as one of the world’s leading conferences in the field of intensive care medicine. Every January, we attract researchers for the best critical care trials published during the previous year to come to Belfast and discuss their work. Such is the quality of analysis and conversation at the conference, we have now become a leading player in hosting original trial results also. In January 2020, we will welcome a host of internationally renowned scientists and clinicians to present and discuss new data which has the potential to change practice worldwide, as well as examine the best critical care trials published during 2019.  

Of particular interest are the highly anticipated results from three key trials – VITAMINS, PEPTIC and 65 – as well as the landmark IHME Sepsis Study, which will be presented in conjunction with their publications in top tier general medical journals and will also be live-streamed globally. A key aim of Critical Care Reviews is to make scientific discovery accessible to all and the data being presented at the conference underscores our efforts to promote research and scientific advancement in this complex area of medicine. 

With over 400 delegates expected to attend from around the world, #CCR20 promises to be an exciting and potentially game-changing conference that will report the latest discoveries and medical advancements in the field of critical care medicine.” 

To register to attend #CCR20 at Titanic Belfast on 16-17 January 2020, please visit www.criticalcarereviews.com.  

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ABOUT VITAMINS 

VITAMINS is a multicentre, randomised, open-label controlled phase 2 trial of 216 participants to determine whether combination therapy of vitamin C, thiamine and hydrocortisone in patients with septic shock increases duration of time alive and free of vasopressor administration, compared with hydrocortisone therapy alone. 

Secondary outcome measures include ICU mortality (90 days after randomisation), alive and ICU-free days at day 28, hospital mortality (90 days after randomisation), 28-day mortality, 90-day mortality, delta of sequential organ failure assessment (SOFA) score at 72 hours, hospital length of stay (90 days after randomisation), 28 day cumulative vasopressor free hours, 28 day cumulative invasive mechanical ventilation free hours and renal replacement therapy (RRT) duration (28 days after randomisation).  

Registered via ClinicalTrials.gov, identification No. NCT03333278. Available here: https://clinicaltrials.gov/ct2/show/NCT03333278?term=NCT03333278&draw=2&rank=1