TRansfusion Strategies in Acute Brain INjured Patients

Traumatic Brain Injury Clinical Trial

— TRAIN  

Official title:

TRansfusion Strategies in Acute Brain INjured Patients: TRAIN Study: A Prospective Multicenter Randomized Interventional Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02962349
• Other study ID #: TRAIN
• Status: Recruiting
• Phase: N/A
• First received: November 4, 2016
• Last updated: November 10, 2016
• Start date: September 2016
• Est. completion date: December 2020

Study information

• Verified date: November 2016
• Source: European Society of Intensive Care Medicine
• Contact: Fabio S TACCONE, MD, PhD
• Phone: +3225555587
• Email: ftaccone[@]ulb.ac.be
• Is FDA regulated: No
• Health authority: Belgium: European Society of Intensive Care medicine
• Study type: Interventional

Clinical Trial Summary

A Prospective Multicenter Randomized Interventional Study. Blood transfusion can be lifesaving in extreme circumstances, in the absence of life threatening hemorrhage, the indications for transfusion are somewhat controversial. The aim of the current study is to determine whether a"liberal" strategy of maintaining Hb concentrations above 9 g/dL would result in a different neurological outcome when compared to a "restrictive" approach to red-cell transfusion to avoid hemoglobin concentrations < 7 g/dL in critically ill anemic patients (i.e. Hb< 9 g/dL) with acute brain injury.

Description:

Background: Although blood transfusions can be lifesaving in severe hemorrhage, they could also result in several potential complications. As anemia has also been associated with poor outcome in critically ill patients,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 cerebro-vascular reserve, which adjust cerebral blood flow to tissue oxygen demand.

Methods/Design: The investigators describe herein the methodology of a prospective, multicenter, randomized, pragmatic trial comparing two different strategies to initiate red blood cells transfusions in patients with acute brain injury: a "liberal" strategy, which aims to maintain hemoglobin(Hb) concentrations above 9 g/dL and a "restrictive" approach to blood transfusion that maintains hemoglobin concentrations above 7 g/dL. Target population includes patients suffering from traumatic brain injury (TBI), subarachnoid hemorrhage (SAH) and intracranial hemorrhage (ICH). The primary outcome is neurological outcome, evaluated using extended Glasgow Outcome Scale (eGOS), at 180 days after the initial injury. Secondary outcomes include, amongst all, 28-day survival, intensive care unit (ICU) and hospital length of stay, the occurrence of extra-cerebral organ dysfunction/failure and the development of any infection or thromboembolic events (either venous or arterial). The estimated sample size to demonstrate a reduction in the primary outcome between groups from 50% to 45% is 4610 patients (2305 for each arm). The study will be initiated in 2015 within several European ICUs and conducted over 4 years.

Expected outcomes/Discussion: This trial will assess the impact of two different strategies to administer blood transfusions in a large cohort of critically ill patients with a primary brain injury. The results of this trial may help to better manage blood products and transfusion thresholds in this specific patients‟ population and will provide additional data in some sub-groups of patients at high-risk of brain ischemia, such as those with an intracranial hypertension or developing cerebral vasospasm.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4610
• Est. completion date: December 2020
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Age =18 years and = 80 years

2. Acute Brain Injury: Traumatic Brain Injury; Subarachnoid Hemorrhage; Intracranial Hemorrhage

3. Glasgow Coma Score (GCS) on randomization< 12

4. Expected ICU stay > 72 hours

5. Hemoglobin (Hb) concentration < 9 g/dL

Exclusion Criteria:

6. Post-anoxic coma; status epilepticus without underlying brain injury; central nervous system (CNS) infections (community-acquired; hospital-acquired; ventriculitis; post-operative)

7. Known previous neurological disease, causing significant cognitive and/or motor handicap

8. ICH due to artero-venous malformation (AVM) or brain tumor

9. Inability (religious reasons) or reduced ability (lack of compatible blood) to receive blood products

10. Active and uncontrolled bleeding at the time of enrollment

11. GCS of 3 with both fixed and dilated pupils; Brain death or imminent death (within 24 hours)

12. Pregnancy

13. Medical need to correct anemia (e.g. active coronary disease or severe cardiac disease) with target Hb levels > 9 g/dL

14. DNE (do not escalate) orders

15. Previous adverse event with transfusion

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Brain Injuries
• Hemorrhage
• Intracranial Hemorrhages
• Subarachnoid Hemorrhage
• Traumatic Brain Injury

Intervention

Biological:
• Red blood cell transfusion
Red blood cell transfusion at various doses

Locations

Country	Name	City	State
Belgium	All Centers From All Over the World Willing to Contribute Are Welcome	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
European Society of Intensive Care Medicine

Country where clinical trial is conducted

Belgium, 

References & Publications (10)

Blumberg N, Heal JM. Immunomodulation by blood transfusion: an evolving scientific and clinical challenge. Am J Med. 1996 Sep;101(3):299-308. Review. — View Citation

Carson JL, Duff A, Poses RM, Berlin JA, Spence RK, Trout R, Noveck H, Strom BL. Effect of anaemia and cardiovascular disease on surgical mortality and morbidity. Lancet. 1996 Oct 19;348(9034):1055-60. — View Citation

Carson JL, Poses RM, Spence RK, Bonavita G. Severity of anaemia and operative mortality and morbidity. Lancet. 1988 Apr 2;1(8588):727-9. — View Citation

Fransen E, Maessen J, Dentener M, Senden N, Buurman W. Impact of blood transfusions on inflammatory mediator release in patients undergoing cardiac surgery. Chest. 1999 Nov;116(5):1233-9. — View Citation

Hare GM. Anaemia and the brain. Curr Opin Anaesthesiol. 2004 Oct;17(5):363-9. — View Citation

Hébert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999 Feb 11;340(6):409-17. Erratum in: N Engl J Med 1999 Apr 1;340(13):1056. — View Citation

Ness PM. Transfusion medicine: an overview and update. Clin Chem. 2000 Aug;46(8 Pt 2):1270-6. Review. — View Citation

Toy P, Feiner J, Viele MK, Watson J, Yeap H, Weiskopf RB. Fatigue during acute isovolemic anemiain healthy, resting humans. Transfusion. 2000 Apr;40(4):457-60. — View Citation

Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A, Meier-Hellmann A, Nollet G, Peres-Bota D; ABC (Anemia and Blood Transfusion in Critical Care) Investigators.. Anemia and blood transfusion in critically ill patients. JAMA. 2002 Sep 25;288(12):1499-507. — View Citation

Vincent JL, Sakr Y, Sprung C, Harboe S, Damas P; Sepsis Occurrence in Acutely Ill Patients (SOAP) Investigators.. Are blood transfusions associated with greater mortality rates? Results of the Sepsis Occurrence in Acutely Ill Patients study. Anesthesiology. 2008 Jan;108(1):31-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurological outcome at 180 days after brain injury	neurological outcome evaluated using extended Glasgow Outcome Scale (eGOS)	180 days	No
Secondary	28-day survival parameter 1	Monitoring eGOS changes over time	28 days	No
Secondary	28-day survival parameter 2	Monitoring mRS changes over time	28 days	No
Secondary	ICU and hospital length of stay	length of stay	28 days	No
Secondary	The occurrence of extra-cerebral organ dysfunction/failure	Extra-cerebral organ dysfunction/failure: composite outcome (death and/or organ dysfunction/failure)	28 days	No
Secondary	Infection rate	The development of any infection or thromboembolic events (either venous or arterial)	28 days	No