FFP In Traumatic BRAin INjury (FIT-BRAIN) Trial

Multi-institutional Phase 2/3 Trial of Fresh Frozen Plasma (FFP) in Patients With Moderate to Severe Traumatic Brain Injury (TBI)

The goal of this clinical trial is to learn about treatment with fresh frozen plasma (FFP) in individuals with moderate to severe traumatic brain injury. The two main question[s]it aims to answer are:

• Is the FFP treatment safe?

• Does the FFP treatment impact the 24-hour, 3-month and 6-month outcomes, intensive-care free days, mortality, and hospital brain and physical function at discharge. Patients with moderate to severe TBI will randomly receive either:

  • Standard of care treatment
  • Standard of care treatment + 2 units of FFP. Researchers will compare participants receiving standard of care treatment to those receiving experimental fresh frozen plasma (FFP) treatment to see if the FFP is safe and beneficial to participant outcomes.

Study Overview

• Status: Recruiting
• Conditions: Moderate to Severe Traumatic Brain Injury
• Intervention / Treatment: Biological: Fresh Frozen Plasma (FFP)

Detailed Description

The two units of fresh frozen plasma will consist of 400-500 ml. The 24-hour, 3-month and 6-month outcome measures include hemorrhagic progression of contusion (HPC) measured on 24-hour follow-up CT scan, the Disability Rating Score (DRS), 24-hour Glasgow Coma Scale (GCS) and the 3-month and 6-month Extended Glasgow Outcome Score (GOS-E).

A third sub aim of the trial is to establish peripheral blood biomarkers, and radiographic features on the initial cross- sectional imaging, that could identify the optimal target population and predict the response to treatment.

• Study Type: Interventional
• Enrollment (Estimated): 357
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Hasan Alam, MD; Phone Number: 312-926-4962; Email: Hasan.Alam@nm.org
• Study Contact Backup: Name: Nicole Meredyth, MD; Phone Number: 312-694-4867; Email: nicole.meredyth@nm.org

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Contact: Nicole Meredyth, MD; Phone Number: 312-694-4867; Email: nicole.meredyth@nm.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female between the ages of 18 and 65 years
2. Moderate to severe TBI: GCS 3-12
3. Cerebral trauma confirmed on the initial CT scan with radiographic findings consistent with Brain Injury Guidelines category 3 (BIG 3).
4. The potential participant's wallet, when present, was examined and no power of attorney related to blood product administration was identified.

Exclusion Criteria:

1. Persons with a known history of adverse reaction to plasma products.
2. Persons with a known history of congestive heart failure, renal failure, liver failure, or severe respiratory dysfunction requiring home use of supplemental oxygen.
3. Persons who are currently incarcerated.
4. Persons with inadequate venous access.
5. Treatment cannot start within 1 hour of arrival at the hospital.
6. The time of injury is unknown.
7. Non-survivable injuries in the estimation of the attending trauma and/or neurosurgeon.
8. Interfacility transfers
9. Class 3 hemorrhagic shock
10. Persons with known "do not resuscitate" orders prior to randomization
11. Persons who refuse the administration of blood products
12. Persons with a research "opt out" bracelet
13. Persons who require FFP for any other indication (e.g., reversal of coagulopathy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care; Standard of Care Control Group
Experimental: Standard of Care + FFP; Standard of Care + Experimental Treatment	Biological: Fresh Frozen Plasma (FFP); Standard of Care + 2 units (400-500 ml) of fresh frozen plasma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extended Glasgow Outcome Scale (GOS-E)	Scoring values range from 1 to 8 with higher scores representing a better outcome. 1 indicates death, 2 indicates a vegetative state, 3 or 4 indicates severe disability, 5 or 6 indicates moderate disability, and 7 or 8 indicates good recovery.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemorrhagic progression of the contusion (HPC)	We will quantify HPC as the change in volume of the largest contiguous brain lesion in mm. This will be measured through a comparison of the initial and the follow-up CT scan.	The first 24 hour post-injury
Disability Rating Scale (DRS)	This scale includes eight categories: A. Eye opening (0-5), B. Communication ability (0-4), C. Motor response (0-5), D. Feeding - cognitive ability only (0-3), E. Toileting - cognitive ability only (0-3), F. Grooming - cognitive ability only (0-3), G. Level of functioning - physical, mental, emotional or social function (0-5) and H. "Employability" - a full time worker, homemaker, or student (0-3). Higher scores in each category mean a worse outcome.	Discharge or day 7 of the hospital stay and 3 months post-injury

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disability Rating Scale (DRS)	This scale includes eight categories: A. Eye opening (0-5), B. Communication ability (0-4), C. Motor response (0-5), D. Feeding - cognitive ability only (0-3), E. Toileting - cognitive ability only (0-3), F. Grooming - cognitive ability only (0-3), G. Level of functioning - physical, mental, emotional or social function (0-5) and H. "Employability" - a full time worker, homemaker, or student (0-3). Higher scores in each category mean a worse outcome.	6 months post-injury
Extended Glasgow Outcome Scale (GOS-E)	Scoring values range from 1 to 8, with higher scores representing a better outcome. 1 indicates death, 2 indicates a vegetative state, 3 or 4 indicates severe disability, 5 or 6 indicates moderate disability, and 7 or 8 indicates good recovery.	6 months post-injury
Time to treatment	Time to treatment measured in hours and minutes.	The first 24 hours post-injury
Contusion volume	Total contusion volume measured in mm3	The first 24 hours post-injury
Non-contiguous contusions	Count of non-contiguous contusions	The first 24 hours post-injury
Glasgow Coma Scale (GCS)	This scale uses three behavior categories to measure response with larger numbers and total score representing a better outcome. They are: Eye opening response (4-1), Best verbal response (5-1) and Best motor response (6-1). Of the total score 15=Best response, 8 or less = Comatose client and 3=Totally unresponsive.	The first 24 hours post-injury
TBI severity sub-stratification using the Glasgow Coma Scale (GCS)	his scale uses three behavior categories to measure response with larger numbers and total score representing a better outcome. They are: Eye opening response (4-1), Best verbal response (5-1) and Best motor response (6-1). Of the total score 15=Best response, 8 or less = Comatose client and 3=Totally unresponsive. (GCS 9-12) = moderate and (GCS 3-8)=severe	The first 24 hours post-injury

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: University of Alabama at Birmingham; University of Southern California; Medical College of Wisconsin; University of California, Davis; Oregon Health and Science University; Vanderbilt University Medical Center; University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Hasan Alam, MD, Northwestern University

Publications and helpful links

General Publications

• Joseph B, Obaid O, Dultz L, Black G, Campbell M, Berndtson AE, Costantini T, Kerwin A, Skarupa D, Burruss S, Delgado L, Gomez M, Mederos DR, Winfield R, Cullinane D; AAST BIG Multi-institutional Study Group. Validating the Brain Injury Guidelines: Results of an American Association for the Surgery of Trauma prospective multi-institutional trial. J Trauma Acute Care Surg. 2022 Aug 1;93(2):157-165. doi: 10.1097/TA.0000000000003554. Epub 2022 Mar 28.
• Liggett MR, Lashley S, Gill NP, Scholtens DM, Dawood ZS, Alam HB. Plasma therapy for traumatic brain injury: Rationale for a prospective randomized trial. Transfusion. 2024 Jul;64(7):1362-1371. doi: 10.1111/trf.17928. Epub 2024 Jun 28. No abstract available.
• Jin G, Liggett MR, Ho JW, Dawood ZS, Chtraklin K, Diaz D, Alam HB. Plasma treatment is associated with decreased brain lesion and resuscitation requirements after traumatic brain injury in a swine model of prolonged damage-control resuscitation. J Trauma Acute Care Surg. 2024 Dec 1;97(6):954-960. doi: 10.1097/TA.0000000000004457. Epub 2024 Oct 15.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: September 13, 2023
• First Submitted That Met QC Criteria: September 25, 2023
• First Posted (Actual): October 2, 2023

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: TBI; Traumatic Brain Injury; Fresh frozen plasma; FFP
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: PR212312; CDMRP-W81XWH2211106 (Other Grant/Funding Number: United States Department of Defense)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No