Transfusion-requirements in Septic Shock Trial (TRISS)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Copenhagen Trial Unit, Center for Clinical Intervention Research
Rigshospitalet, Denmark
University of Copenhagen
Information provided by (Responsible Party):
Anders Perner, Scandinavian Critical Care Trials Group
ClinicalTrials.gov Identifier:
NCT01485315
First received: November 30, 2011
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
Septic Shock
Biological: SAGM (Saline-Adenine-Glucose-Mannitol) blood transfusion
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Red Blood Cell Transfusion on Mortality and Morbidity in Patients With Septic Shock

Resource links provided by NLM:


Further study details as provided by Scandinavian Critical Care Trials Group:

Primary Outcome Measures:
  • Mortality [ Time Frame: 90 day ] [ Designated as safety issue: No ]
    All cause 90 day mortality


Secondary Outcome Measures:
  • Persistent organ failure [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    Defined as need for ventilation, vasopressor/inotrope infusion or renal replacement therapy

  • Persistent organ failure [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    Defined as need for ventilation, vasopressor/inotrope infusion or renal replacement therapy

  • Persistent organ failure [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    Defined as need for ventilation, vasopressor/inotrope infusion or renal replacement therapy

  • Anaphylactic/allergic reactions [ Time Frame: Followed up until ICU discharge; an expected average of one week ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Followed up until ICU discharge; an expected average of one week ] [ Designated as safety issue: Yes ]
    Defined by the clinician on the basis of haemoglobinuria or increased free plasma haemoglobin.

  • Transfusion associated acute lung injury (TRALI) [ Time Frame: Followed up until ICU discharge; an expected average of one week ] [ Designated as safety issue: Yes ]

    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


  • Transfusion associated circulatory overload (TACO) [ Time Frame: Followed up until ICU discharge; an expected average of one week ] [ Designated as safety issue: Yes ]

    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 balance


  • Ischaemic events [ Time Frame: Followed up until ICU discharge; an expected average of one week ] [ Designated as safety issue: Yes ]
    Defined as either myocardial, cerebral, intestinal or acute limb ischaemia

  • Days alive without life support [ Time Frame: 90-days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Mortality within the whole observation period [ Time Frame: One year after randomisation of the last patient ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Physical and mental component summary scores of SF 36


Estimated Enrollment: 1000
Study Start Date: November 2011
Estimated Study Completion Date: May 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Liberal blood transfusion
Blood transfusion at haemoglobin 9.0 g/dl (5.6 mM) or less
Biological: 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
Other Name: Liberal red blood cell (RBC) transfusion
Active Comparator: Restrictive blood transfusion
Blood transfusion at haemoglobin 7.0 g/dl (4.3 mM) or less
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
Other Name: Restrictive red blood cell (RBC) transfusion

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01485315

Locations
Denmark
Aarhus University Hospital, Skejby
Aarhus, Denmark
Aarhus University Hospital, NBG
Aarhus, Denmark
Glostrup Hospital
Copenhagen, Denmark
Bispebjerg Hospital
Copenhagen, Denmark
Hvidovre Hospital
Copenhagen, Denmark
Rigshospitalet
Copenhagen, Denmark
Gentofte Hospital
Gentofte, 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
Ålborg University Hospital
Ålborg, Denmark
Finland
Helsinki University Hospital
Helsinki, Finland
Joensuu Hospital
Joensuu, Finland
Tampere University Hospital
Tampere, Finland
Norway
Haukeland University Hospital
Bergen, Norway
Akershus University Hospital
Oslo, Norway
Stavanger University Hospital
Stavanger, Norway
Ålesund Hospital
Ålesund, Norway
Sweden
Halmstad Hospital
Halmstad, Sweden
Helsingborg Hospital
Helsingborg, Sweden
Karolinska Institutet Solna
Stockholm, Sweden
Södersjukhuset
Stockholm, Sweden
Karolinska Hospital, Huddinge
Stockholm, Sweden
Växjö Hospital
Växjö, Sweden
Sponsors and Collaborators
Scandinavian Critical Care Trials Group
Copenhagen Trial Unit, Center for Clinical Intervention Research
Rigshospitalet, Denmark
University of Copenhagen
Investigators
Principal Investigator: Anders Perner, MD, PhD Dept. of Intensive Care, Rigshospitalet / SCCTG
  More Information

Publications:
Responsible Party: Anders Perner, Principle Investigator, Scandinavian Critical Care Trials Group
ClinicalTrials.gov Identifier: NCT01485315     History of Changes
Other Study ID Numbers: H-3-2011-114
Study First Received: November 30, 2011
Last Updated: May 29, 2014
Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics
Denmark: Danish Dataprotection Agency
Norway: Regional Ethics Commitee
Sweden: Regional Ethical Review Board
Finland: Ethics Committee

Additional relevant MeSH terms:
Shock
Shock, Septic
Pathologic Processes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Mannitol
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 01, 2014