TRansfusion Strategies in Acute Brain INjured Patients (TRAIN)

Transfusion Strategies in Acute Brain Injured Patients. A Prospective Multicenter Randomized Study.

To compare a "liberal" and a "restrictive" strategy to administer blood transfusions in critically ill patients with a primary brain injury.

Study Overview

• Status: Completed
• Conditions: Blood Transfusion; Acute Brain Injury
• Intervention / Treatment: Procedure: Restrictive Transfusion Strategy; Procedure: Liberal Transfusion Strategy

Detailed Description

Although blood transfusions can be lifesaving in severe hemorrhage, they can also have potential complications. As anemia has also been associated with poor outcomes in critically ill patients, determining an optimal transfusion trigger is a real challenge for clinicians. This is even more important in patients with acute brain injury who were not specifically evaluated in previous large randomized clinical trials dealing with the optimal transfusion threshold. Neurological patients may be particularly sensitive to anemic brain hypoxia because of the exhausted cerebrovascular reserve, which adjusts cerebral blood flow to tissue oxygen demand.

This prospective, multicenter, randomized, pragmatic trial will compare two different strategies for red blood cell transfusion in patients with acute brain injury: a "liberal" strategy in which the aim is to maintain hemoglobin (Hb) concentrations greater than 9 g/dL and a "restrictive" approach in which the aim is to maintain Hb concentrations greater than 7 g/dL. The target population is patients suffering from traumatic brain injury (TBI), subarachnoid hemorrhage (SAH) or intracranial hemorrhage (ICH).

The primary outcome is neurological outcome, evaluated using the extended Glasgow Outcome Scale (eGOS), at 180 days after the initial injury. Secondary outcomes include, amongst others, 28-day survival, intensive care unit (ICU) and hospital lengths of stay, the occurrence of extra-cerebral organ dysfunction/failure and the development of any infection or thromboembolic events (venous or arterial).

The estimated sample size is 794 patients to demonstrate a reduction in the primary outcome (i.e. unfavorable neurological outcome) from 50% to 30% between groups (397 patients in each arm). The study will be initiated in September 2016 in several European ICUs and is expected at least 6 years.

The results of this trial will help to improve blood product and transfusion use in this specific patient population and will provide additional data in some sub-groups of patients at high-risk of brain ischemia, such as those with intracranial hypertension or cerebral vasospasm.

• Study Type: Interventional
• Enrollment (Actual): 850
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fabio S Taccone, MD, PhD; Phone Number: +3225555587; Email: ftaccone@ulb.ac.be
• Study Contact Backup: Name: Dominique Durand; Phone Number: +3225555580; Email: ddurand@ulb.ac.be

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • Hopital Erasme

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Glasgow Coma Score (GCS) ≤ 13 on randomization
• Expected ICU stay > 72 hours
• hemoglobin (Hb) concentration ≤ 9 g/dL within 10 days from brain injury

Exclusion Criteria:

1. Post-anoxic coma; status epilepticus without underlying brain injury; central nervous system (CNS) infections (community-acquired; hospital-acquired; ventriculitis; post-operative)
2. Known previous neurological disease, causing significant cognitive and/or motor handicap
3. ICH due to arterio-venous malformation (AVM) or brain tumor
4. Inability (religious reasons) or reduced ability (lack of compatible blood) to receive blood products
5. Active and uncontrolled bleeding at the time of enrollment
6. GCS of 3 with both pupils fixed and dilated; brain death or imminent death (within 24 hours)
7. Pregnancy
8. Medical need to correct anemia (e.g., active coronary disease or severe cardiac disease) with target Hb levels > 9 g/dL
9. do-not-escalate (DNE) orders
10. Previous allo-immunization due to transfusion, limiting red blood cells (RBC) availability

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Restrictive Transfusion Strategy; "Blood Transfusion" will be given when hemoglobin concentration will be below 7 g/dL (as suggested by current guidelines in "general" ICU population)	Procedure: Restrictive Transfusion Strategy; Patients will be randomized when hemoglobin levels will be below 9 g/dl. Patients randomized to the "Restrictive Transfusion Strategy" will receive blood transfusion whenever their Hb concentration is < 7 g/dl. All patients should preferably receive one unit of blood transfusion at a time. The duration of the intervention is 28 days after randomization or until hospital discharge. Daily assessment of hemoglobin levels are mandatory only during the ICU stay. No other procedures and or interventions are scheduled. General management of patients will be conducted according to international guidelines; however, local protocols and procedures are allowed.
Other: Liberal Transfusion Strategy; "Blood Transfusion" will be given when hemoglobin concentration will be below 9 g/dL	Procedure: Liberal Transfusion Strategy; Patients will be randomized when hemoglobin levels will be below 9 g/dl. Patients randomized to the "Liberal Transfusion Strategy" will receive blood transfusion whenever their Hb concentration is < 7 g/dl. All patients should preferably receive one unit of blood transfusion at a time. The duration of the intervention is 28 days after randomization or until hospital discharge. Daily assessment of hemoglobin levels are mandatory only during the ICU stay. No other procedures and or interventions are scheduled. General management of patients will be conducted according to international guidelines; however, local protocols and procedures are allowed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unfavorable Neurological Outcome	Unfavorable neurological outcome is defined by the extended Glasgow Outcome Scale (eGOS) of 1-5	180 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	28 days Survival	28 days
Changes in the Glasgow Coma Score (GCS) over time	modification of GCS from admission over the first week and vs. the last available	28 days
ICU length of stay	length of ICU stay	180 days
Hospital length of stay	length oh hospital stay	180 days
Presence and severity of extra-cerebral organ dysfunction/failure	Daily sequential organ failure assessment (SOFA) score	28 days
Infection rate	Occurrence of any infection over the first 28 days after randomization	28 days
Composite outcome	Death and Organ Failure (defined as at least one extra-cerebral organ failure, according to the specific SOFA sub-score > 2)	28 days
Brain Oxygen Pressure	Absolute values of brain oxygen pressure (PbO2) for those patients where this neuromonitoring has been implemented, according to the decision of the attending physician	28 days
Daily Fluid Balance	Assessment of the daily fluid balance	28 days
Serious Adverse Events (SAE)	Any of the "SAE" as described in the study protocol	28 days

Collaborators and Investigators

• Sponsor: Erasme University Hospital
• Collaborators: European Society of Intensive Care Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2016
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: November 11, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (Estimated): November 18, 2016

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Blood Transfusion; Hemoglobin; Outcome; Brain Injury
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries
• Other Study ID Numbers: P2015/327

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO