Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial

Lars B Holst, Nicolai Haase, Jørn Wetterslev, Jan Wernerman, Anders Aneman, Anne B Guttormsen, Pär I Johansson, Sari Karlsson, Gudmundur Klemenzson, Robert Winding, Lars Nebrich, Carsten Albeck, Marianne L Vang, Hans-Henrik Bülow, Jeanie M Elkjær, Jane S Nielsen, Peter Kirkegaard, Helle Nibro, Anne Lindhardt, Ditte Strange, Katrin Thormar, Lone M Poulsen, Pawel Berezowicz, Per M Bådstøløkken, Kristian Strand, Maria Cronhjort, Elsebeth Haunstrup, Omar Rian, Anders Oldner, Asger Bendtsen, Susanne Iversen, Jørn-Åge Langva, Rasmus B Johansen, Niklas Nielsen, Ville Pettilä, Matti Reinikainen, Dorte Keld, Siv Leivdal, Jan-Michael Breider, Inga Tjäder, Nanna Reiter, Ulf Gøttrup, Jonathan White, Jørgen Wiis, Lasse Høgh Andersen, Morten Steensen, Anders Perner, Lars B Holst, Nicolai Haase, Jørn Wetterslev, Jan Wernerman, Anders Aneman, Anne B Guttormsen, Pär I Johansson, Sari Karlsson, Gudmundur Klemenzson, Robert Winding, Lars Nebrich, Carsten Albeck, Marianne L Vang, Hans-Henrik Bülow, Jeanie M Elkjær, Jane S Nielsen, Peter Kirkegaard, Helle Nibro, Anne Lindhardt, Ditte Strange, Katrin Thormar, Lone M Poulsen, Pawel Berezowicz, Per M Bådstøløkken, Kristian Strand, Maria Cronhjort, Elsebeth Haunstrup, Omar Rian, Anders Oldner, Asger Bendtsen, Susanne Iversen, Jørn-Åge Langva, Rasmus B Johansen, Niklas Nielsen, Ville Pettilä, Matti Reinikainen, Dorte Keld, Siv Leivdal, Jan-Michael Breider, Inga Tjäder, Nanna Reiter, Ulf Gøttrup, Jonathan White, Jørgen Wiis, Lasse Høgh Andersen, Morten Steensen, Anders Perner

Abstract

Background: Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients.

Methods/design: The Transfusion Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin level (Hb) of 7 g/dl or 9 g/dl, stratified by the presence of haematological malignancy and centre. The primary outcome measure is 90-day mortality. Secondary outcome measures are organ failure, ischaemic events, severe adverse reactions (SARs: anaphylactic reaction, acute haemolytic reaction and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year.The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed after 500 patients, and the Data Monitoring and Safety Committee will recommend the trial be stopped if a group difference in 90-day mortality with P ≤0.001 is present at this point.

Discussion: The TRISS trial may bridge the gap between clinical practice and the lack of efficacy and safety data on RBC transfusion in septic shock patients. The effect of restrictive versus liberal RBC transfusion strategy on mortality, organ failure, ischaemic events and SARs will be evaluated.

Trial registration: ClinicalTrials.gov NCT01485315.

Figures

Figure 1
Figure 1
Transfusion trigger levels in Denmark. The figure shows the lowest haemoglobin level measured 0 to 2 hours before red blood cell (RBC) transfusion in 213 consecutive septic shock patients in 7 Danish ICUs. The data represent 358 transfused units of saline-adenine-glucose-mannitol (SAGM) [20]. To convert values in mM to g/l multiply with 1.6.
Figure 2
Figure 2
Transfusion requirements in septic shock (TRISS) trial flow diagram.
Figure 3
Figure 3
Trial status. Print from the ransfusion equirements n eptic hock (TRISS) electronic Case Record Form showing the trial status on 19 April 2013.
Figure 4
Figure 4
Organisational diagram.

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