TRansfusion Strategies in Acute Brain INjured Patients

Erasme University Hospital850 enrolled

Overview

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

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

850

Conditions

Acute Brain Injury Blood Transfusion

Interventions

Restrictive Transfusion StrategyPROCEDURE

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.

Liberal Transfusion StrategyPROCEDURE

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (1)

Hopital Erasme

Brussels, Belgium

Outcomes

Primary Outcomes

Unfavorable Neurological Outcome

Unfavorable neurological outcome is defined by the extended Glasgow Outcome Scale (eGOS) of 1-5

Time frame: 180 days after randomization

Secondary Outcomes

Survival

28 days Survival

Time frame: 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

Time frame: 28 days

ICU length of stay

length of ICU stay

Time frame: 180 days

Hospital length of stay

length oh hospital stay

Time frame: 180 days

Presence and severity of extra-cerebral organ dysfunction/failure

Daily sequential organ failure assessment (SOFA) score

Time frame: 28 days

Infection rate

Occurrence of any infection over the first 28 days after randomization

Time frame: 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)

Time frame: 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

Data from ClinicalTrials.gov

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