TRansfusion Strategies in Acute Brain INjured Patients

Not Applicable

Completed

• Conditions: Acute Brain Injury; Blood Transfusion
• Interventions: Procedure: Restrictive Transfusion Strategy; Procedure: Liberal Transfusion Strategy

• Registration Number: NCT02968654
• Lead Sponsor: Erasme University Hospital

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.

Study Timeline

• Study Start: 2016-09-13
• Study First Submitted: 2016-11-11
• Study First Submitted QC: 2016-11-16
• Study First Posted: 2016-11-18
• Primary Completion: 2022-12-31
• Study Completion: 2023-06-30
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-05
• Last Update Posted: 2023-09-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 850

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Restrictive Transfusion Strategy	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)
Liberal Transfusion Strategy	Liberal Transfusion Strategy	"Blood Transfusion" will be given when hemoglobin concentration will be below 9 g/dL

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Hopital Erasme; 🇧🇪 Brussels, Belgium