Transfusion-requirements in Septic Shock Trial
- Conditions
- Septic Shock
- Interventions
- Biological: SAGM (Saline-Adenine-Glucose-Mannitol) blood transfusion
- Registration Number
- NCT01485315
- Lead Sponsor
- Scandinavian Critical Care Trials Group
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1005
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Liberal blood transfusion SAGM (Saline-Adenine-Glucose-Mannitol) blood transfusion Blood transfusion at haemoglobin 9.0 g/dl (5.6 mM) or less Restrictive blood transfusion SAGM (Saline-Adenine-Glucose-Mannitol) blood transfusion Blood transfusion at haemoglobin 7.0 g/dl (4.3 mM) or less
- Primary Outcome Measures
Name Time Method Mortality 90 day All cause 90 day mortality
- Secondary Outcome Measures
Name Time Method Persistent organ failure Day 28 Defined as need for ventilation, vasopressor/inotrope infusion or renal replacement therapy
Anaphylactic/allergic reactions Followed up until ICU discharge; an expected average of one week Defined by the clinician on the basis of mucocutaneous signs and symptoms (e.g. urticaria, pruritus, localised angio- oedema).
Haemolytic complications after transfusion of RBC Followed up until ICU discharge; an expected average of one week Defined by the clinician on the basis of haemoglobinuria or increased free plasma haemoglobin.
Transfusion associated acute lung injury (TRALI) Followed up until ICU discharge; an expected average of one week TRALI defined as:
I. Acute or worsening hypoxaemia ((PaO2/FiO2 \< 40 (PaO2 in kPa) or \<300 (PaO2 in mmHg) regardless of PEEP) OR \> 50% relative increase in FiO2.
AND II. Occurrence within 6 hours after RBC transfusion AND III. Acute or worsening pulmonary infiltrates on frontal chest x-ray OR clinical signs of overt pulmonary oedemaTransfusion associated circulatory overload (TACO) Followed up until ICU discharge; an expected average of one week TACO defined as:
I. Acute or worsening hypoxaemia ((PaO2/FiO2 \< 40 (PaO2 in kPa) or \<300 (PaO2 in mmHg) regardless of PEEP) OR \> 50% relative increase in FiO2.
AND II. Occurrence within 6 hours after RBC transfusion AND III. Acute or worsening pulmonary infiltrates on frontal chest x-ray OR clinical signs of overt pulmonary oedema AND IV. Increased blood pressure AND VI. Positive fluid balanceIschaemic events Followed up until ICU discharge; an expected average of one week Defined as either myocardial, cerebral, intestinal or acute limb ischaemia
Days alive without life support 90-days Life support defined as need for ventilation, vasopressor/inotrope infusion or renal replacement therapy. Days alive without each of these interventions will be reported
Days alive and out of hospital 90 days Mortality within the whole observation period One year after randomisation of the last patient Mortality within the whole observation period reported at day 28, six-month and 1 year after randomisation of the last patient.
Health-related quality of life 1 year Physical and mental component summary scores of SF 36
Trial Locations
- Locations (32)
Ålesund Hospital
🇳🇴Ålesund, Norway
Gentofte Hospital
🇩🇰Gentofte, Denmark
Rigshospitalet
🇩🇰Copenhagen, Denmark
Hjørring Hospital
🇩🇰Hjørring, Denmark
Kolding Hospital
🇩🇰Kolding, 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
Ålborg University Hospital
🇩🇰Ålborg, Denmark
Joensuu Hospital
🇫🇮Joensuu, Finland
Tampere University Hospital
🇫🇮Tampere, Finland
Haukeland University Hospital
🇳🇴Bergen, Norway
Stavanger University Hospital
🇳🇴Stavanger, Norway
Akershus University Hospital
🇳🇴Oslo, Norway
Karolinska Hospital, Huddinge
🇸🇪Stockholm, Sweden
Halmstad Hospital
🇸🇪Halmstad, Sweden
Växjö Hospital
🇸🇪Växjö, Sweden
Helsingborg Hospital
🇸🇪Helsingborg, Sweden
Södersjukhuset
🇸🇪Stockholm, Sweden
Karolinska Institutet Solna
🇸🇪Stockholm, Sweden
Aarhus University Hospital, NBG
🇩🇰Aarhus, Denmark
Aarhus University Hospital, Skejby
🇩🇰Aarhus, Denmark
Bispebjerg Hospital
🇩🇰Copenhagen, Denmark
Glostrup Hospital
🇩🇰Copenhagen, Denmark
Hvidovre Hospital
🇩🇰Copenhagen, Denmark
Herning Hospital
🇩🇰Herning, Denmark
Holbæk Hospital
🇩🇰Holbæk, Denmark
Horsens Hospital
🇩🇰Horsens, Denmark
Køge Hospital
🇩🇰Køge, Denmark