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TRansfusion Strategies in Acute Brain INjured Patients (TRAIN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02968654
Recruitment Status : Recruiting
First Posted : November 18, 2016
Last Update Posted : October 17, 2022
Sponsor:
Collaborator:
European Society of Intensive Care Medicine
Information provided by (Responsible Party):
Fabio Taccone, Erasme University Hospital

Tracking Information
First Submitted Date  ICMJE November 11, 2016
First Posted Date  ICMJE November 18, 2016
Last Update Posted Date October 17, 2022
Actual Study Start Date  ICMJE September 13, 2016
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 13, 2022)		 Unfavorable Neurological Outcome [ Time Frame: 180 days after randomization ]
Unfavorable neurological outcome is defined by the extended Glasgow Outcome Scale (eGOS) of 1-5
Original Primary Outcome Measures  ICMJE
 (submitted: November 16, 2016)		 Good Neurological Outcome [ Time Frame: 180 days after randomization ]
Good neurological outcome is defined by the extended Glasgow Outcome Scale (eGOS) of 6-8
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2020)
  • Survival [ Time Frame: 28 days ]
    28 days Survival
  • Changes in the Glasgow Coma Score (GCS) over time [ Time Frame: 28 days ]
    modification of GCS from admission over the first week and vs. the last available
  • ICU length of stay [ Time Frame: 180 days ]
    length of ICU stay
  • Hospital length of stay [ Time Frame: 180 days ]
    length oh hospital stay
  • Presence and severity of extra-cerebral organ dysfunction/failure [ Time Frame: 28 days ]
    Daily sequential organ failure assessment (SOFA) score
  • Infection rate [ Time Frame: 28 days ]
    Occurrence of any infection over the first 28 days after randomization
  • Composite outcome [ Time Frame: 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 [ Time Frame: 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
  • Daily Fluid Balance [ Time Frame: 28 days ]
    Assessment of the daily fluid balance
  • Serious Adverse Events (SAE) [ Time Frame: 28 days ]
    Any of the "SAE" as described in the study protocol
Original Secondary Outcome Measures  ICMJE
 (submitted: November 16, 2016)
  • Survival [ Time Frame: 28 days ]
  • Changes in the Glasgow Coma Score (GCS) over time [ Time Frame: 28 days ]
  • ICU length of stay [ Time Frame: 180 days ]
  • Hospital length of stay [ Time Frame: 180 days ]
  • Presence and severity of extra-cerebral organ dysfunction/failure [ Time Frame: 28 days ]
    Daily sequential organ failure assessment (SOFA) score
  • Infection rate [ Time Frame: 28 days ]
    Occurrence of any infection over the first 28 days after randomization
  • Composite outcome [ Time Frame: 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 [ Time Frame: 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
  • Daily Fluid Balance [ Time Frame: 28 days ]
    Assessment of the daily fluid balance
  • Serious Adverse Events (SAE) [ Time Frame: 28 days ]
    Any of the "SAE" as described in the study protocol
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TRansfusion Strategies in Acute Brain INjured Patients
Official Title  ICMJE Transfusion Strategies in Acute Brain Injured Patients. A Prospective Multicenter Randomized Study.
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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Brain Injury
  • Blood Transfusion
Intervention  ICMJE
  • 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.
  • Procedure: 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.
Study Arms  ICMJE
  • 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)
    Intervention: Procedure: Restrictive Transfusion Strategy
  • Liberal Transfusion Strategy
    "Blood Transfusion" will be given when hemoglobin concentration will be below 9 g/dL
    Intervention: Procedure: Liberal Transfusion Strategy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 13, 2022)		 794
Original Estimated Enrollment  ICMJE
 (submitted: November 16, 2016)		 4610
Estimated Study Completion Date  ICMJE July 30, 2023
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Fabio S TACCONE, MD, PhD +3225555587 ftaccone@ulb.ac.be
Contact: Dominique Durand +3225555580 ddurand@ulb.ac.be
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02968654
Other Study ID Numbers  ICMJE P2015/327
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Fabio Taccone, Erasme University Hospital
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Erasme University Hospital
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE European Society of Intensive Care Medicine
Investigators  ICMJE Not Provided
PRS Account Erasme University Hospital
Verification Date October 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP