Transfusion-requirements in Septic Shock Trial

Septic Shock Clinical Trial

— TRISS  

Official title:

Effects of Red Blood Cell Transfusion on Mortality and Morbidity in Patients With Septic Shock

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01485315
• Other study ID #: H-3-2011-114
• Status: Completed
• Phase: Phase 3
• First received: November 30, 2011
• Last updated: October 2, 2014
• Start date: November 2011
• Est. completion date: April 2014

Study information

• Verified date: October 2014
• Source: Scandinavian Critical Care Trials Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research EthicsDenmark: Danish Dataprotection AgencyNorway: Regional Ethics CommiteeSweden: Regional Ethical Review BoardFinland: Ethics Committee
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 1005
• Est. completion date: April 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

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
• 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

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital, NBG	Aarhus
Denmark	Aarhus University Hospital, Skejby	Aarhus
Denmark	Ålborg University Hospital	Ålborg
Denmark	Bispebjerg Hospital	Copenhagen
Denmark	Glostrup 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	Køge Hospital	Køge
Denmark	Kolding Hospital	Kolding
Denmark	Næstved Hospital	Næstved
Denmark	Randers Hospital	Randers
Denmark	Slagelse Hospital	Slagelse
Denmark	Sønderborg Hospital	Sønderborg
Denmark	Vejle Hospital	Vejle
Finland	Helsinki University Hospital	Helsinki
Finland	Joensuu Hospital	Joensuu
Finland	Tampere University Hospital	Tampere
Norway	Ålesund Hospital	Ålesund
Norway	Haukeland University Hospital	Bergen
Norway	Akershus University Hospital	Oslo
Norway	Stavanger University Hospital	Stavanger
Sweden	Halmstad Hospital	Halmstad
Sweden	Helsingborg Hospital	Helsingborg
Sweden	Karolinska Hospital, Huddinge	Stockholm
Sweden	Karolinska Institutet Solna	Stockholm
Sweden	Södersjukhuset	Stockholm
Sweden	Växjö Hospital	Växjö

Sponsors (4)

Lead Sponsor	Collaborator
Scandinavian Critical Care Trials Group	Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Denmark, University of Copenhagen

Countries where clinical trial is conducted

Denmark,  Finland,  Norway,  Sweden, 

References & Publications (2)

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, Bülow HH, Elkjær JM, Nielsen JS, Kirkegaard P, Nibro H, Lindhardt A, Strange D, Thormar K, Poulsen LM, Berezowicz P, Bådstøløkken PM, Strand K, Cronhjort M, Haunstrup E, Rian O, Oldner A, Bendtsen A, Iversen S, Langva JÅ, Johansen RB, Nielsen N, Pettilä V, Reinikainen M, Keld D, Leivdal S, Breider JM, Tjäder I, Reiter N, Gøttrup 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. — View 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, Pettilä V, Cronhjort MB, Andersen LH, Pedersen UG, Reiter N, Wiis J — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality	All cause 90 day mortality	90 day	No
Secondary	Persistent organ failure	Defined as need for ventilation, vasopressor/inotrope infusion or renal replacement therapy	Day 5	No
Secondary	Persistent organ failure	Defined as need for ventilation, vasopressor/inotrope infusion or renal replacement therapy	Day 14	No
Secondary	Persistent organ failure	Defined as need for ventilation, vasopressor/inotrope infusion or renal replacement therapy	Day 28	No
Secondary	Anaphylactic/allergic reactions	Defined by the clinician on the basis of mucocutaneous signs and symptoms (e.g. urticaria, pruritus, localised angio- oedema).	Followed up until ICU discharge; an expected average of one week	Yes
Secondary	Haemolytic complications after transfusion of RBC	Defined by the clinician on the basis of haemoglobinuria or increased free plasma haemoglobin.	Followed up until ICU discharge; an expected average of one week	Yes
Secondary	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	Followed up until ICU discharge; an expected average of one week	Yes
Secondary	Transfusion associated circulatory overload (TACO)	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	Followed up until ICU discharge; an expected average of one week	Yes
Secondary	Ischaemic events	Defined as either myocardial, cerebral, intestinal or acute limb ischaemia	Followed up until ICU discharge; an expected average of one week	Yes
Secondary	Days alive without life support	Life support defined as need for ventilation, vasopressor/inotrope infusion or renal replacement therapy. Days alive without each of these interventions will be reported	90-days	No
Secondary	Days alive and out of hospital		90 days	No
Secondary	Mortality within the whole observation period	Mortality within the whole observation period reported at day 28, six-month and 1 year after randomisation of the last patient.	One year after randomisation of the last patient	No
Secondary	Health-related quality of life	Physical and mental component summary scores of SF 36	1 year	No