TRansfusion Strategies in Acute Brain INjured Patients

Blood Transfusion Clinical Trial

— TRAIN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02968654
• Other study ID #: P2015/327
• Status: Completed
• Phase: N/A
• Start date: September 13, 2016
• Est. completion date: June 30, 2023

Study information

• Verified date: September 2023
• Source: Erasme University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Other known NCT identifiers

• NCT02962349

Recruitment information / eligibility

• Status: Completed
• Enrollment: 850
• Est. completion date: June 30, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Brain Injury
• Blood Transfusion
• Brain Injuries

Intervention

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.
• 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.

Locations

Country	Name	City	State
Belgium	Hopital Erasme	Brussels

Sponsors (2)

Lead Sponsor	Collaborator
Erasme University Hospital	European Society of Intensive Care Medicine

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Unfavorable Neurological Outcome	Unfavorable neurological outcome is defined by the extended Glasgow Outcome Scale (eGOS) of 1-5	180 days after randomization
Secondary	Survival	28 days Survival	28 days
Secondary	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
Secondary	ICU length of stay	length of ICU stay	180 days
Secondary	Hospital length of stay	length oh hospital stay	180 days
Secondary	Presence and severity of extra-cerebral organ dysfunction/failure	Daily sequential organ failure assessment (SOFA) score	28 days
Secondary	Infection rate	Occurrence of any infection over the first 28 days after randomization	28 days
Secondary	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
Secondary	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
Secondary	Daily Fluid Balance	Assessment of the daily fluid balance	28 days
Secondary	Serious Adverse Events (SAE)	Any of the "SAE" as described in the study protocol	28 days