Transfusion-requirements in Septic Shock Trial

NCT ID: NCT01485315

Last Updated: 2014-10-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1005 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2014-04-30

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

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Liberal blood transfusion

Blood transfusion at haemoglobin 9.0 g/dl (5.6 mM) or less

Group Type: ACTIVE_COMPARATOR

SAGM (Saline-Adenine-Glucose-Mannitol) blood transfusion

Intervention Type: BIOLOGICAL

One unit prestorage, leuko-depleted SAGM blood at haemoglobin at 9.0 g/dl (5.6 mM) or less at point-of-care testing

Restrictive blood transfusion

Blood transfusion at haemoglobin 7.0 g/dl (4.3 mM) or less

Group Type: ACTIVE_COMPARATOR

SAGM (Saline-Adenine-Glucose-Mannitol) blood transfusion

Intervention Type: BIOLOGICAL

One unit prestorage, leuko-depleted SAGM blood at haemoglobin 7.0 g/dl (4.3 mM) or less at point-of-care testing

Interventions

SAGM (Saline-Adenine-Glucose-Mannitol) blood transfusion

One unit prestorage, leuko-depleted SAGM blood at haemoglobin at 9.0 g/dl (5.6 mM) or less at point-of-care testing

Intervention Type: BIOLOGICAL

SAGM (Saline-Adenine-Glucose-Mannitol) blood transfusion

One unit prestorage, leuko-depleted SAGM blood at haemoglobin 7.0 g/dl (4.3 mM) or less at point-of-care testing

Intervention Type: BIOLOGICAL

Other Intervention Names

Liberal red blood cell (RBC) transfusion; Restrictive red blood cell (RBC) transfusion

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Copenhagen Trial Unit, Center for Clinical Intervention Research

OTHER

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: collaborator

University of Copenhagen

OTHER

Sponsor Role: collaborator

Scandinavian Critical Care Trials Group

OTHER

Sponsor Role: lead

Responsible Party

Anders Perner

Principle Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anders Perner, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Intensive Care, Rigshospitalet / SCCTG

Locations

Ålborg University Hospital

Aalborg, , Denmark

Aarhus University Hospital, NBG

Aarhus, , Denmark

Aarhus University Hospital, Skejby

Aarhus, , Denmark

Bispebjerg Hospital

Copenhagen, , Denmark

Glostrup Hospital

Copenhagen, , Denmark

Hvidovre Hospital

Copenhagen, , Denmark

Rigshospitalet

Copenhagen, , Denmark

Gentofte Hospital

Gentofte Municipality, , Denmark

Herning Hospital

Herning, , Denmark

Hjørring Hospital

Hjørring, , Denmark

Holbæk Hospital

Holbæk, , Denmark

Horsens Hospital

Horsens, , Denmark

Kolding Hospital

Kolding, , Denmark

Køge Hospital

Køge, , Denmark

Næstved Hospital

Næstved, , Denmark

Randers Hospital

Randers, , Denmark

Slagelse Hospital

Slagelse, , Denmark

Sønderborg Hospital

Sønderborg, , Denmark

Vejle Hospital

Vejle, , Denmark

Helsinki University Hospital

Helsinki, , Finland

Joensuu Hospital

Joensuu, , Finland

Tampere University Hospital

Tampere, , Finland

Ålesund Hospital

Ålesund, , Norway

Haukeland University Hospital

Bergen, , Norway

Akershus University Hospital

Oslo, , Norway

Stavanger University Hospital

Stavanger, , Norway

Halmstad Hospital

Halmstad, , Sweden

Helsingborg Hospital

Helsingborg, , Sweden

Karolinska Hospital, Huddinge

Stockholm, , Sweden

Karolinska Institutet Solna

Stockholm, , Sweden

Södersjukhuset

Stockholm, , Sweden

Växjö Hospital

Vaxjo, , Sweden

Countries

Denmark; Finland; Norway; Sweden

References

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.

Reference Type: BACKGROUND

PMID: 23702006 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25270275 (View on PubMed)

Carson JL, Stanworth SJ, Dennis JA, Fergusson DA, Pagano MB, Roubinian NH, Turgeon AF, Valentine S, Trivella M, Doree C, Hebert PC. Transfusion thresholds and other strategies for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2025 Oct 20;10:CD002042. doi: 10.1002/14651858.CD002042.pub6.

Reference Type: DERIVED

PMID: 41114449 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34932836 (View on PubMed)

Other Identifiers

H-3-2011-114

Identifier Type: -

Identifier Source: org_study_id