The mission of the Irish Critical Care – Clinical Trials Group (ICC-CTG) is to undertake high quality research in the Critical Care field in Ireland, including basic science research, multi-centre clinical trials, informatics and service delivery and organisation research with a view to translating this knowledge into inproving clinical practice.
The ICC-CTG is accountable to the Council of the Intensive Care Society of Ireland (ICSI). An Executive Committee, that is a sub-committee of the ICSI Council, administers the ICC-CTG. A Chair, Vice-Chair, Secretary and Tresurar are elected by the Executive Committee for three years. All members and office bearers (chair, vice-chair and past chair) of the Executive have a renewable tenure of three years.
The ICC-CTG memebership shall in the first instance comprise the lead investigator for each participating site in the group. The committee structure will be representative of intensive care medicine clinical and academic practice in Ireland, with a basic principle of inclusivity rather than exclusivity.
Participation in ICC-CTG studies shall be at the discretion of the Executive and will be dependent upon previous participation record.
will establish whether the way we ‘set’ the breathing machine helps reduce further lung damage in patients with a severe lung disease (Acute Respiratory Distress Syndrome ARDS). A small research study by some of the group members showed that reducing the size of each breath in conjunction with an occasional sustained deep breath, through the ventilator appeared to reduce further damage to the lungs. But the study size was too small to make definitive conclusions. So a larger study, which this network now makes possible, will assess whether patients with ARDS are better off on this PHARLAP breathing strategy.
TRANSFUSE – Does giving ‘fresher’ blood versus “older blood” in transfusions make a difference to patients who are admitted to ICU. This study will result in a worldwide practice change if it finds freshest available blood us best but if there is no difference this will provide great confidence to blood banks that current practice is optimal.
The network will also carry out test studies to determine which of the common treatments to help reduce bleeding from the stomach when people are very unwell is best. The network will also provide extra training for junior doctors and nurses in Ireland, so they can be future world leaders in research within the Irish health system.
Sedation Practices in Intensive Care Evaluation: SPICE III: A Prospective Multicentre Randomised Controlled Trial of Early Goal-Directed Sedation Compared with Standard Care in Mechanically Ventilated Patients in Intensive Care A prospective, un-blinded, randomised controlled trial of Early Goal-Directed Sedation (EGDS) compared with standard care. The study will recruit patients who are intubated and ventilated in a participating ICU, are expected to remain intubated the day after enrolment and need immediate and ongoing sedation.
Over the last decade clinical practice has changed somewhat towards the use of lighter levels of sedation whenever clinically safe, better management of pain, and
recognition of delirium as occurring commonly in patients with critical illness.
A number of studies suggest that the centrally mediated alpha2 agonist sedative dexmedetomidine facilitates rousable sedation, shortens ventilation time, and attenuates the occurrence of delirium, and may therefore be advantageous compared to other sedatives. Whether these potential advantages are associated with improvement in patientcentred outcomes, such as longterm mortality and cognitive function, is unknown.
The primary aim of this study is to determine whether Early Goal-Directed Sedation, compared to standard care sedation, reduces 90-day mortality in critically ill patients who are expected to require mechanical ventilation for longer than 24 hours.
The study will compare a strategy of early titrated light sedation (early goal directed sedation) to standard sedation practices in critically ill patients ventilated for >24 hours. The primary aim of this study is to determine whether Early GoalDirected Sedation, compared to standard care sedation, reduces 90day mortality in critically ill patients who are expected to require mechanical ventilation for longer than 24 hours. The study is an international multicentre trial which in total will recruit 4000 patients.
This program acts as an observational study, without any intervention, and involves collecting data on topics of interest, in patients in multiple intensive care units, on a specific day or days. It provides no information on outcomes, but provides very important information on how common a problem is, and what is currently being done to manage that problem. This is an ongoing program consisting of multiple research collection days, each performing multiple, independent studies simultaneously, including a number of paediatric studies.
The Point Prevalence studies are purely observational, and no intervention is required by the study protocol. The collected data will be entered via a secure password-protected encrypted website (RedCAP).
This project is a prospective, observational, multicentre, single-day, point prevalence study of evidence based processes of care using piloted CRF. Research coordinators from each participating institution collect data on all patients who are present in the ICU on the study day. Only fully de-identified data is released to the program’s management centre.
The ARISE RCT was a multi-centre, randomised controlled trial of the effect of early goal-directed therapy, compared to standard care, on 90-day mortality in patients presenting to the Emergency Department with severe sepsis.
Patients were randomised in the ED to receive either EGDT for a total of 6 hours post-randomisation, or standard care. Patients assigned to receive EGDT were cared for by the dedicated ARISE study team. The patient received treatment as per the study protocol for 6 hours with central blood oxygen levels as the target end-point, and then received standard care. Patients assigned to receive standard care continued to be cared for by the hospital team in accordance with current best practice. Patients in both groups received any additional treatment needed, such as antibiotics or surgery.
The study was conducted in multiple sites with 1600 patients enrolled in the study over a 2.5 year period.
Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay.
In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days
(Hydroxymethylglutaryl- CoA reductase inhibition in Acute lung injury to Reduce Pulmonary dysfunction – a multi-centre RCT)
Studies in animals and in vitro and phase 2 studies in humans suggest that statins may be beneficial in the treatment of the acute respiratory distress syndrome (ARDS). This study tested the hypothesis that treatment with simvastatin would improve clinical outcomes in patients with ARDS.
In this multicenter, double-blind clinical trial, we randomly assigned (in a 1:1 ratio) patients with an onset of ARDS within the previous 48 hours to receive enteral simvastatin at a dose of 80 mg or placebo once daily for a maximum of 28 days. The primary outcome was the number of ventilator-free days to day 28. Secondary outcomes included the number of days free of nonpulmonary organ failure to day 28, mortality at 28 days, and safety.
The study recruited 540 patients, with 259 patients assigned to simvastatin and 281 to placebo. The groups were well matched with respect to demographic and baseline physiological variables. There was no significant difference between the study groups in the mean (±SD) number of ventilator-free days (12.6±9.9 with simvastatin and 11.5±10.4 with placebo, P=0.21) or days free of nonpulmonary organ failure (19.4±11.1 and 17.8±11.7, respectively; P=0.11) or in mortality at 28 days (22.0% and 26.8%, respectively; P=0.23). There was no significant difference between the two groups in the incidence of serious adverse events related to the study drug.
Protocol for a multicentre randomised controlled trial of early and sustained prophylactic hypothermia in the management of traumatic brain injury.
Nichol A, Gantner D, Presneill J, Murray L, Trapani T, Bernard S, Cameron P, Capellier G, Forbes A, McArthur C, Newby L, Rashford S, Rosenfeld JV, Smith T, Stephenson M, Varma D, Walker T, Webb S, Cooper DJ. Crit Care Resusc. 2015 Jun;17(2):92-100. PMID: 26017126
Erythropoietin in traumatic brain injury: study protocol for a randomised controlled trial.
Nichol A, French C, Little L, Presneill J, Cooper DJ, Haddad S, Duranteau J, Huet O, Skrifvars M, Arabi Y, Bellomo R;EPO-TBI Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Trials. 2015 Feb 8;16:39. doi: 10.1186/s13063-014-0528-6. PMID: 25884605
A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis.
Kruger P1, Bailey M, Bellomo R, Cooper DJ, Harward M, Higgins A, Howe B, Jones D, Joyce C, Kostner K,McNeil J, Nichol A, Roberts MS, Syres G, Venkatesh B; ANZ-STATInS Investigators–ANZICS Clinical Trials Group. Am J Respir Crit Care Med. 2013 Apr 1;187(7):743-50. doi: 10.1164/rccm.201209-1718OC.
Long-term quality of life in patients with acute respiratory distress syndrome requiring extracorporeal membrane oxygenation for refractory hypoxaemia.
Hodgson CL, Hayes K, Everard T, Nichol A, Davies AR, Bailey MJ, Tuxen DV, Cooper DJ, Pellegrino V.
Crit Care. 2011;15(3):R133. doi: 10.1186/cc10249.
A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome.
Hodgson CL1, Tuxen DV, Davies AR, Bailey MJ, Higgins AM, Holland AE, Keating JL, Pilcher DV,Westbrook AJ, Cooper DJ, Nichol AD. Epub 2011 Jun 2. Crit Care. 2012 Oct 19;16(5):R202. doi: 10.1186/cc11811
Age of red blood cells and mortality in the critically ill.
Pettilä V, Westbrook AJ, Nichol AD, Bailey MJ, Wood EM, Syres G, Phillips LE, Street A, French C, Murray L, Orford N, Santamaria JD, Bellomo R, Cooper DJ; Blood Observational Study Investigators for ANZICS Clinical Trials Group. Crit Care. 2011;15(2):R116. doi: 10.1186/cc10142. Epub 2011 Apr 15.
Critical care services and 2009 H1N1 influenza in Australia and New Zealand.
ANZIC Influenza Investigators, Webb SA, Pettilä V, Seppelt I, Bellomo R, Bailey M, Cooper DJ, Cretikos M,Davies AR, Finfer S, Harrigan PW, Hart GK, Howe B, Iredell JR, McArthur C, Mitchell I, Morrison S, Nichol AD, Paterson DL, Peake S, Richards B, Stephens D, Turner A, Yung M. N Engl J Med. 2009 Nov 12;361(20):1925-34. doi: 10.1056/NEJMoa0908481. Epub 2009 Oct 8.
Infection-induced lung injury is worsened after renal buffering of hypercapnic acidosis.
Nichol AD1, O’Cronin DF, Howell K, Naughton F, O’Brien S, Boylan J, O’Connor C, O’Toole D, Laffey JG,McLoughlin P. Crit Care Med. 2009 Nov;37(11):2953-61. doi: 10.1097/CCM.0b013e3181b028ce.
Sustained hypercapnic acidosis during pulmonary infection increases bacterial load and worsens lung injury.
O’Croinin DF1, Nichol AD, Hopkins N, Boylan J, O’Brien S, O’Connor C, Laffey JG, McLoughlin P. Crit Care Med. 2008 Jul;36(7):2128-35. doi: 10.1097/CCM.0b013e31817d1b59.
ICC-CTG Inagural Meeting
In September we held the first inaugural stand alone ICC-CTG meeting in Newman House, UCD. This meeting was an opportunity for collaborators to discuss a number of topics relating to the ICC-CTG as a group, including updating the terms of reference, the website and the future of the trials group as a whole.
This meeting also gave us an opportunity to discuss the Irish Critical Care- Clinical Research Centre (ICC-CRC) which has recently launched its website, detailing the various research clinical trials being carried out. Details of each of these clinical trials including TRANSFUSE, PHARLAP, SPRINT-SARI, STARRT-AKI, SPICE and Point Prevalence can be found on the ICC-CRC website.