Clinical trial NCT02968654: TRansfusion Strategies in Acute Brain INjured Patients
Official title: Transfusion Strategies in Acute Brain Injured Patients. A Prospective Multicenter Randomized Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Brain Injury
Blood Transfusion
Keywords: Blood Transfusion
Brain Injury
Outcome
Hemoglobin
Lead sponsor: Erasme University Hospital
Sponsor class: OTHER
Collaborators: name: European Society of Intensive Care Medicine
First posted: 2016-11-18
Enrollment: 850
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Unfavorable Neurological Outcome
timeFrame: 180 days after randomization
Secondary outcomes:
measure: Survival
timeFrame: 28 days
measure: Changes in the Glasgow Coma Score (GCS) over time
timeFrame: 28 days
measure: ICU length of stay
timeFrame: 180 days
measure: Hospital length of stay
timeFrame: 180 days
measure: Presence and severity of extra-cerebral organ dysfunction/failure
timeFrame: 28 days
measure: Infection rate
timeFrame: 28 days
measure: Composite outcome
timeFrame: 28 days
measure: Brain Oxygen Pressure
timeFrame: 28 days
measure: Daily Fluid Balance
timeFrame: 28 days
measure: Serious Adverse Events (SAE)
timeFrame: 28 days
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Hopital Erasme
Study officials:
References: