Transfusion-requirements in Septic Shock Trial

Background Septic patients often receive red blood cell (RBC) transfusions in the intensive care unit. The evidence that RBC transfusion leads to improved outcome is limited and the intervention may be harmful to some of these patients. In contrast, current guidelines recommend restrictive transfusion of RBC for critical ill patients without septic shock. To bridge the gap between clinical practice and evidence, a large randomised clinical trial is needed to document the efficacy and safety of RBC transfusion in patients with septic shock

Design Pragmatic, multicenter, randomised, outcome assessment-blinded trial of patients with septic shock to RBC transfusion at haemoglobin (Hb) transfusion trigger of 7 g/dl (4.4 mM) or 9 g/dl (5.6 mM), stratified by the presence of haematological malignancy and centre.

Inclusion and exclusion criteria:

To increase the validity of the trial inclusion criteria will be broad with few exclusions

Outcome measures The outcome measures will mainly be patient-important but ICU- and hospital length of stay will also be assessed

Trial size 2 x 500 patients will be needed to show a 9% absolute risk difference in 90-day mortality (baseline mortality of 45%, relative risk reduction 20% (from septic patients in the TRICC trial), alpha of 0.05 (two-sided) and a beta of 0.20 that is a power of 80% (1-beta).

An interim-analysis will be performed after 500 patients. The Data Safety and Monitoring Board (DMSC) will recommend that the trial is stopped if a group-difference in 90-day mortality with p<0.001.

Time Line The first patient is expected to be randomised December 1st 2011 and the trial database is expected to be closed early 2014. The main manuscript will be submitted shortly thereafter.

Funding The trial is publicly funded by the Danish Strategic Research Council