Clinical trial NCT01485315: Transfusion-requirements in Septic Shock Trial
Official title: Effects of Red Blood Cell Transfusion on Mortality and Morbidity in Patients With Septic Shock
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Septic Shock
Lead sponsor: Scandinavian Critical Care Trials Group
Sponsor class: OTHER
Collaborators: name: Copenhagen Trial Unit, Center for Clinical Intervention Research
name: Rigshospitalet, Denmark
name: University of Copenhagen
First posted: 2011-12-05
Enrollment: 1005
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients with blood poisoning - sepsis - often receive blood transfusions in the intensive care unit. The evidence that blood transfusion leads to improved outcome is limited and the blood may be harmful to some of these patients. 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 these very sick patients

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* Patient in the ICU AND
* Fulfil the criteria for septic shock AND
* Have haemoglobin of 9.0 g/dl (5.6 mM) or less AND
* Consent obtainable from patient or proxy or national law allows delayed consent

Exclusion Criteria:

* Documented wish against transfusion OR
* Previous serious adverse reaction with blood product OR
* Acute coronary syndrome OR
* Life-threatening bleeding OR
* RBC transfusion during current ICU admission OR
* Withdrawal from active therapy or brain death OR
* Lack of informed consent (depending on national law) OR
* Acute burn injury regardless of degree and burn surface area

Primary outcomes:
measure: Mortality
timeFrame: 90 day
Secondary outcomes:
measure: Persistent organ failure
timeFrame: Day 5
measure: Persistent organ failure
timeFrame: Day 14
measure: Persistent organ failure
timeFrame: Day 28
measure: Anaphylactic/allergic reactions
timeFrame: Followed up until ICU discharge; an expected average of one week
measure: Haemolytic complications after transfusion of RBC
timeFrame: Followed up until ICU discharge; an expected average of one week
measure: Transfusion associated acute lung injury (TRALI)
timeFrame: Followed up until ICU discharge; an expected average of one week
measure: Transfusion associated circulatory overload (TACO)
timeFrame: Followed up until ICU discharge; an expected average of one week
measure: Ischaemic events
timeFrame: Followed up until ICU discharge; an expected average of one week
measure: Days alive without life support
timeFrame: 90-days
measure: Days alive and out of hospital
timeFrame: 90 days
measure: Mortality within the whole observation period
timeFrame: One year after randomisation of the last patient
measure: Health-related quality of life
timeFrame: 1 year
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital, NBG
city: Aarhus
country: Denmark
facility: Aarhus University Hospital, Skejby
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
city: Copenhagen
country: Denmark
facility: Glostrup Hospital
city: Copenhagen
country: Denmark
facility: Hvidovre Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Gentofte
country: Denmark
facility: Gentofte Hospital
city: Herning
country: Denmark
facility: Herning Hospital
city: Hjørring
country: Denmark
facility: Hjørring Hospital
city: Holbæk
country: Denmark
facility: Holbæk Hospital
city: Horsens
country: Denmark
facility: Horsens Hospital
city: Kolding
country: Denmark
facility: Kolding Hospital
city: Køge
country: Denmark
facility: Køge Hospital
city: Næstved
country: Denmark
facility: Næstved Hospital
city: Randers
country: Denmark
facility: Randers Hospital
city: Slagelse
country: Denmark
facility: Slagelse Hospital
city: Sønderborg
country: Denmark
facility: Sønderborg Hospital
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Ålborg
country: Denmark
facility: Ålborg University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Joensuu
country: Finland
facility: Joensuu Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Akershus University Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Ålesund
country: Norway
facility: Ålesund Hospital
city: Halmstad
country: Sweden
facility: Halmstad Hospital
city: Helsingborg
country: Sweden
facility: Helsingborg Hospital
city: Stockholm
country: Sweden
facility: Karolinska Hospital, Huddinge
city: Stockholm
country: Sweden
facility: Karolinska Institutet Solna
city: Stockholm
country: Sweden
facility: Södersjukhuset
city: Växjö
country: Sweden
facility: Växjö Hospital
Study officials:
affiliation: Dept. of Intensive Care, Rigshospitalet / SCCTG
name: Anders Perner, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Holst LB, Haase N, Wetterslev J, Wernerman J, Aneman A, Guttormsen AB, Johansson PI, Karlsson S, Klemenzson G, Winding R, Nebrich L, Albeck C, Vang ML, Bulow HH, Elkjaer JM, Nielsen JS, Kirkegaard P, Nibro H, Lindhardt A, Strange D, Thormar K, Poulsen LM, Berezowicz P, Badstolokken PM, Strand K, Cronhjort M, Haunstrup E, Rian O, Oldner A, Bendtsen A, Iversen S, Langva JA, Johansen RB, Nielsen N, Pettila V, Reinikainen M, Keld D, Leivdal S, Breider JM, Tjader I, Reiter N, Gottrup U, White J, Wiis J, Andersen LH, Steensen M, Perner A. 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. Trials. 2013 May 23;14:150. doi: 10.1186/1745-6215-14-150.
citation: Holst LB, Haase N, Wetterslev J, Wernerman J, Guttormsen AB, Karlsson S, Johansson PI, Aneman A, Vang ML, Winding R, Nebrich L, Nibro HL, Rasmussen BS, Lauridsen JR, Nielsen JS, Oldner A, Pettila V, Cronhjort MB, Andersen LH, Pedersen UG, Reiter N, Wiis J, White JO, Russell L, Thornberg KJ, Hjortrup PB, Muller RG, Moller MH, Steensen M, Tjader I, Kilsand K, Odeberg-Wernerman S, Sjobo B, Bundgaard H, Thyo MA, Lodahl D, Maerkedahl R, Albeck C, Illum D, Kruse M, Winkel P, Perner A; TRISS Trial Group; Scandinavian Critical Care Trials Group. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014 Oct 9;371(15):1381-91. doi: 10.1056/NEJMoa1406617. Epub 2014 Oct 1.
citation: Carson JL, Stanworth SJ, Dennis JA, Trivella M, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2021 Dec 21;12(12):CD002042. doi: 10.1002/14651858.CD002042.pub5.