Transfusion-requirements in Septic Shock Trial

Scandinavian Critical Care Trials Group1,005 enrolled

Overview

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

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

1,005

Conditions

Septic Shock

Interventions

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

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

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

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (32)

Ålborg University Hospital

Aalborg, Denmark

Outcomes

Primary Outcomes

Mortality

All cause 90 day mortality

Time frame: 90 day

Secondary Outcomes

Persistent organ failure

Defined as need for ventilation, vasopressor/inotrope infusion or renal replacement therapy

Time frame: Day 5

Persistent organ failure

Defined as need for ventilation, vasopressor/inotrope infusion or renal replacement therapy

Time frame: Day 14

Persistent organ failure

Defined as need for ventilation, vasopressor/inotrope infusion or renal replacement therapy

Time frame: Day 28

Anaphylactic/allergic reactions

Defined by the clinician on the basis of mucocutaneous signs and symptoms (e.g. urticaria, pruritus, localised angio- oedema).

Time frame: Followed up until ICU discharge; an expected average of one week

Haemolytic complications after transfusion of RBC

Defined by the clinician on the basis of haemoglobinuria or increased free plasma haemoglobin.

Time frame: Followed up until ICU discharge; an expected average of one week

Transfusion associated acute lung injury (TRALI)

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 oedema

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.