SCCTG. Scandinavia Critical Care Trials Group. A research group to facilitate Scandinavian multicenter studies in critical care

Transcription

1 SCCTG Scandinavia Critical Care Trials Group A research group to facilitate Scandinavian multicenter studies in critical care Board Anders Perner Niklas Nielsen Elin Helset Sari Karlsson Gudmundur Klemenzson

2 Publications Oldner A, et al. Survey on vasopressor and inotropic drug therapy in Scandinavian intensive care units. ACTA 2003;47:693 P. Guldbrand et al. Survey of routines for sedation of patients on controlled ventilation in Nordic intensive care units. ACTA 2004;48:944 Gullberg et al. Immediate and 5-year cumulative outcome after paediatric intensive care in Sweden. ACTA 2008;52:1086 A Perner et al. Preferences for colloid use in Scandinavian intensive care units. ACTA 2008;52:750 N Nielsen et al. Outcome, timing and adverse events in therapeutic hypothermia after out-of-hospital cardiac arrest. ACTA 2009;53:926 N Nielsen et al.adverse events and their relation to mortality in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. Crit Care Med 2011;39:57 A Perner et al. Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S - Scandinavian Starch for Severe Sepsis/Septic Shock trial): Study protocol, design and rationale for a double-blinded, randomised clinical trial. Trials 2011;12:24 J Wernerman et al.scandinavian glutamine trial: a pragmatic multi-centre randomised clinical trial of intensive care unit patients. ACTA 2011;55:812 N Nielsen et al.target temperature management after out-of-hospital cardiac arrest-a randomized, parallel-group, assessor-blinded clinical trial - rationale and design. Am Heart J 2012;163:541

3 Ongoing and future trials Two ongoing research programmes Hypothermia after cardiac arrest Resuscitation in sepsis Proposed research programmes Stress ulcer prophylaxis in ICU BRAINOXY Proposed collaboration ADRENAL ANZICS CTG Preliminary discussions AKI programme

4 Hypothermia Network Hypothermia after cardiac arrest Data of the first 1000 pts published Principal investigators Niklas Nielsen Hans Friberg

5 Meta-analysis and trial sequential analysis Five randomised trials (478 patients); all with substantial risk of bias The relative risk for death was 0.84 (95% CI 0.70 to 1.01) For poor neurological outcome 0.78 (95% CI 0.64 to 0.95) Two trials with least risk of bias: RR for death was 0.92 (95% CI 0.56 to 1.51) For poor neurological outcome 0.92 (95% CI 0.56 to 1.50) TSA indicated lack of firm evidence for beneficial effects N Nielsen et al. Int J Cardiol 2011;151:333-41

6 Target Temperature Management TTM trial Multicentric, randomised trial of mild hypothermia after out-of hospital cardiac arrest 34 sites in 10 countries 561 included of the 850 sample size Interim analysis conducted NCT

7 Inclusions Adults with OHCA of presumed cardiac cause AND Return of spontaneous circulation AND Unconsciousness Exclusions OHCA of presumed non-cardiac cause Known bleeding diathesis Suspected or confirmed stroke Unwitnessed asystole Known limitations in therapy Known disease making 180 days survival unlikely Known pre-arrest CPC 3 or 4 Temperature < 30 C on admission > 4 hours from ROSC to screening Systolic blood pressure < 80 mm Hg

8 Intervention 33 vs 36 degrees C for 36 h incl cooling and rewarming Primary outcome measure Mortality at maximum follow-up with a minimum of 180 days Secondary outcome measures Composite death or poor neurological function Neurological function QoL Safety: bleeding, arrythmias, infection, electrolyte disturbances, hypo- and hyperglycemia, use of RRT

9 Sponsors and Collaborators Niklas Nielsen Scandinavian Critical Care Trials Group Copenhagen Trial Unit, Center for Clinical Intervention Research Lund University The George Institute of Global Health, Sydney, Australia Contact Niklas Nielsen

10 5-yr strategic research programme New strategies for resuscitation of patients with severe sepsis Aims Trial 1 Trial 2 Trial 3 To test the safety and efficacy of frequently used resuscitation fluids in severe sepsis through multicentre RCTs The 6S trial Blood transfusion in septic shock - TRISS Plasma transfusion trial in severe sepsis

11 6S 6S trial TRIAL Scandinavian Starch for Severe Sepsis/Septic Shock Trial

12 4S trial 4S TRIAL Scandinavian Study for Severe use of Sjampagne

13 TRISS TRIAL TRISS trial Transfusion-requirements in septic shock SCCTG, Copenhagen Trial Unit and 30 trial sites Steering committee Lars Broksø Holst, Jørn Wetterslev, Pär Johansson, Jan Wernerman, Anders Åneman, Anne Berit Guttormsen, Sari Karlsson, Gudmundur Klemenzson, Nicolai Haase, Anders Perner

14 Blood products use in ICU pts Crit Care 2010;14:R185

15 AIM TRISS TRIAL To assess the effects of two different RBC transfusion triggers on mortality and organ failure in patients with septic shock

16 Inclusions TRISS TRIAL Adult patients who Are in the ICU AND Are aged > 18 years AND Fulfil the criteria for septic shock AND Have Hb < 9 g/dl (5.6 mm) AND Consent obtainable from patient or proxy

17 Inclusions Adult patients who TRISS TRIAL Are in the ICU AND Are aged > 18 years AND Fulfil the criteria for septic shock AND Have Hb < 9 g/dl (5.6 mm) AND Consent obtainable from patient or proxy Exclusions Documented wish against transfusion OR Previous SAR with blood products OR Acute coronary syndrome OR Life threatening bleeding OR RBC transfusion during current ICU admission OR Withdrawal from active therapy

18 80 Hb trigger value in septic shock Design 60 Multicenter, randomised, assessor-blinded trial Tranfusions, n 1000 patients in septic shock TRISS TRIAL 0 SAGM Tx at SAGM Tx at 25-percentil 7 g/dl 75-percentil 9 g/dl

19 1. outcome measure 90-day mortality TRISS TRIAL

20 2. outcome measures TRISS TRIAL 28-d, ½- and 1 year mortality Organ failure at day 5, 14 and 28 Severe adverse reactions SARs Ischaemic events in the ICU Length of stay in ICU and hospital

21 Timeline TRISS TRIAL Sites initiated pts included 1 st patient randomised Dec 3 rd 2011

22 Status May 25th TRISS TRIAL

23 TRISS TRIAL Interested? National investigators Lars Broksø Holst / Anders Perner Jan Wernerman Anne Berit Guttormsen Sari Karlsson Gudmundur Klemenzson

24 Proposed programme Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) A Scandinavian critical care research programme Morten Hylander Møller, MD PhD

25 Research question Should patients in the ICU receive SUP with proton-pump inhibitors?

26 Background Standard of care in the SSC Increased risk of hospital acquired pneumonia and Clostridium difficile colitis? Increased risk of cardiovascular events? Increased risk of mortality in patients receiving EN? The rationale and choice of SUP agent is largely unresolved

27 Research programme 1.An evidence-based review 2.A survey of current practice 3.A cohort study of current practice 4.A randomized clinical trial

28 Interested? Morten Hylander Møller, MD PhD

29 Proposed trial Impact of inspired oxygen fraction on outcome in patients with traumatic brain injury (BRAINOXY) Stepani Bendel, MD, PhD Department of Intensive Care Medicine, Kuopio University Hospital, Finland

30 Aim of the study and hypothesis To investigate the impact of two different fractions of inspired oxygen (0.4 vs. 0.7) on clinical outcome in TBI Hypothesis: High fraction of inspired oxygen will improve outcome in patients with TBI

31 Study design National multicenter study SCCTG study? Future Kuopio University Hospital, Helsinki University Central Hospital (Töölö Hospital), Tampere University Hospital Randomized, open label: FiO2 0,4 and FiO2 0,7 Sample size n=500

32 Inclusion criteria Isolated brain injury / multiple trauma patients with brain injury and unaffected oxygenation Glascow coma score scale 8 or less Need for artificial ventilation >24 hours Exclusion criteria: Age <18 or >65 years, moribund patient, anticipated brain death in 12 hours, need for artificial ventilation < 24 hours, insufficient oxygenation, lack of consent

33 Outcome measurement Outcome at 3 and 6 months Primary: GOS, GOSE, morbidity and mortality Secondary: Combined proportion of unfavourable neurological outcomes at 6 months: severe disability (defined as GOSE scores 2-4) or death (GOSE score 1). Mortality at 6 months Proportion of surviving patients with unfavourable neurological outcome (GOSE 2-4) at 6 months Quality of life assessment (EQ-5D) at 6 months

34 Impact of inspired oxygen fraction on outcome in patients with traumatic brain injury (BRAINOXY) Stepani Bendel, MD, PhD Department of Intensive Care Medicine, Kuopio University Hospital, Finland

35 corticosteroid treatment in critically IlL patients with septic shock Bala Venkatesh John Myburgh Simon Finfer Steve Webb Jeremy Cohen Rinaldo Bellomo Chris Joyce Colin McArthur Parissa Glass Djillali Annane Dorrilyn Rajbhandri Julie French Meg Harward Lynssey Willenberg

36 Aim To determine whether hydrocortisone therapy reduces mortality in patients admitted to an Intensive Care Unit (ICU) with septic shock Hypothesis Hydrocortisone, compared to placebo, reduces 90-day all-cause mortality in patients admitted to an ICU with septic shock

37 Inclusion criteria (All criteria must be met) Age 18 yrs or > Documented site or strong suspicion of infection At least 2 SIRS criteria Shock attributable to sepsis Need for pressors or inotropes to maintain SBP >90 or a MAP > 60 or as determined by the treating clinician Requirement for vasopressors > 4 hrs or > and is present at the time of randomisation Need for positive pressure ventilation (includes BIPAP/CPAP)

38 Intervention 200 mg hydrocortisone/day given as an intravenous infusion over 24 hours for 7 days or till discharge from ICU or 200 mg placebo/day given as an intravenous infusion over 24 hours for 7 days or till discharge from ICU Study treatments supplied in identical vials

39 Outcomes Primary outcome 90 day mortality Secondary outcomes 6 month mortality Duration of IPPV QoL 6 months Shock resolution ICU / Hospital LOS ALI Reintubation / Trache Bacteremias Bleeding RRT

40 Sample size Estimated baseline mortality in septic shock 33% (ANZICS-CTG sepsis surveys / CAT study and global data) 5% ARR or 15% RRR, 90% power Target sample size 3800 patients (1900 in each arm) Co-enrollments allowed

41 Time lines Pilot trial sites June 2012 Other sites August 2012 Investigator meetings May/June 2012 Study expected to run over 4 years

42 Paper work The George Inst. wil do the European Medicines Agency application The research unit at AN/ICU, Rigshospitalet will do the Danish paper work and be the hub to Scandinavia if there are more Scandinavian sites Short Medicines Agency application and ethics and data protection applications for each country

43 Interested?

44 Preliminary discussions AKI programme

45 SCCTG contribute to evidencebased medicine Trials needed on Sedation Antibiotics Oxygen Ventilation Humidifiers Suctioning Fluid therapy Inotropes Vasopressors Resuscitation endpoints Blood products Renal support Nutrition Metabolic control Anticoagulation Ulcer prophylaxis VAP prophylaxis Rehabilitation After care Ethics Staffing Education ICU design and many more...

46 SCCTG Next meeting in Lund May 31st 2012 Agenda Investigator meetings Up-date on current trials Protocol proposals Socialising