TRansfusion Strategies in Acute Brain INjured Patients

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

Detailed Description
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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.

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

Conditions
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Acute Brain Injury, Blood Transfusion

Intervention / Treatment
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* Procedure: Restrictive Transfusion Strategy
* Procedure: Liberal Transfusion Strategy


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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Restrictive Transfusion Strategy<br>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<br>* 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.<br>|
| Other: Liberal Transfusion Strategy<br>Blood Transfusion will be given when hemoglobin concentration will be below 9 g/dL | Procedure: Liberal Transfusion Strategy<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood Transfusion, Brain Injury, Outcome, Hemoglobin