Clinical trial results in critical care medicine to be unveiled at leading UK conference

Monday 16th December 2019: 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.

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Globally, 50 million sepsis patients are treated in hospitals each year,

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with sepsis mortality rates in middle and low income countries reported to be as high as 60%.

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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.

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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.

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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).

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Stress ulcer prophylaxis is prescribed to more than 70% of adults who are acutely admitted to an ICU,

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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.

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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,

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however, it has also shown to be associated with an increase in developing nosocomial pneumonia

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and Clostridium difficile infection.

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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.

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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.

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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,

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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.

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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.

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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,

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and mortality, possibly as high as 60% in low and middle income countries,

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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.”

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

http://www.

criticalcarereviews.

com

.

For more information please contact LK Communications:

Dave Cullen, Director


[email protected]


Tel: +44 (0)28 90427 004

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Geri Wright, Client Director


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Notes to Editors

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

ABOUT PEPTIC

PEPTIC is a multi-centre, randomised, open-label, cluster crossover, registry-embedded phase 2 trial conducted in 50 ICUs in Australia, Canada, Ireland, New Zealand and the United Kingdom with almost 27,000 registered patients. PEPTIC will compare the effect on in-hospital mortality of implementing, at the level of the ICU, the use of PPI as the preferred agent for stress ulcer prophylaxis in mechanically ventilated adults in the ICU compared to use of H2RB as the preferred agent.

Primary end point is in-hospital mortality. Secondary endpoints include clinically significant upper GI bleeding, Clostridium difficile infection, ICU length of stay and hospital length of stay.

Registered via Australian and New Zealand Clinical Trials Registry (ANZCTRN 12616000481471). Available here:

www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370438&isReview=true

ABOUT 65

The 65 trial, led by Chief Investigator, Mr Paul Mouncey and Lead Clinical Investigator (Dr. Francois Lamontagne) evaluates the clinical and cost-effectiveness of permissive hypotension in critically ill patients aged 65 years or over with vasodilatory hypotension when compared with usual care and tests 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.

Primary outcomes are (i) Clinical effectiveness: all-cause mortality at 90 days and (ii) Cost-effectiveness: incremental net monetary benefit (INB), evaluated at the NICE recommended threshold of £20,000 per quality-adjusted life year (QALY), at 90 days.

Secondary outcomes include; mortality at discharge from the critical care unit and acute hospital, duration of survival to longest available follow-up, duration of advanced respiratory and renal support (defined according to the Critical Care Minimum Dataset [CCMDS]) during the critical care unit stay, days alive and free of advanced respiratory support and renal support, duration of critical care unit and acute hospital stay, cognitive function assessed using the Informant Questionnaire on Cognitive Decline in the Elderly at 90 days and one year, resource use and costs at 90 days and one year and estimated lifetime incremental cost-effectiveness.

Registered via the ISRCTN Registry (ISRCTN10580502).

About IHME SEPSIS STUDY

The IHME Sepsis Study has leveraged the Global Burden of Disease Study, a comprehensive worldwide epidemiological investigation produced by the Institute for Health Metrics and Evaluation (IHME), to generate estimates for sepsis incidence and mortality across 195 countries and territories, 282 underlying causes, both sexes, and 23 age groups, for the years 1990 through 2017. This will be the first time extensive data from low and middle income countries has been used to generate an accurate worldwide picture of this devastating condition.

Further information about the IHME Global Burden of Disease project is available at

http://www.

healthdata.

org/

gbd

ABOUT CRITICAL CARE REVIEWS

Critical Care Reviews is a free, not-for-profit, educational critical care project promoting open access to scientific advancement, founded and led by Dr. Rob Mac Sweeney, an intensivist working in Belfast, Northern Ireland. Critical Care Reviews was established in 2009 and its annual meeting is now in its 8th year, bringing together chief investigators for the best critical care trials to present their findings and inform best practice, changing the treatment landscape and promoting scientific advancement in critical care medicine. For more information visit

www.criticalcarereviews.com

.

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