Recruiting

Biomarker-Guided Pathway

Sponsor:

University of Michigan

Code:

NCT07829107

Conditions

Head Injury Trauma

Traumatic Brain Injury, Mild

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Clinical pathway 1: Guidelines plus biomarkers

Clinical guidelines only

Study Details

Brief summary:

This is a pragmatic, open-label, multicenter, stepped-wedge, Type II hybrid effectiveness-implementation study. It is designed to evaluate both the comparative effectiveness and implementation feasibility of a biomarker-plus-clinical guidelines algorithm to reduce low-value brain computed tomography (CT) use in emergency department (ED) patients evaluated for suspected traumatic brain injury (TBI). The biomarkers are Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin Carboxy-terminal Hydrolase L1 (UCH-L1), two brain-injury proteins cleared by the FDA to support brain CT imaging decisions after trauma. All six participating EDs will contribute baseline data for the first 6 months under usual care (clinical guidelines only). Beginning in month 7, two sites will transition to implementing the biomarker-guided algorithm. At month 13, two additional sites will implement the biomarker-guided approach, and the final two sites will transition at month 19. By the end of the 24-month rollout period, all sites will have implemented the biomarker-guided pathway.

Conditions

Head Injury Trauma

Traumatic Brain Injury, Mild

Study ID

NCT07829107

Start date

Oct 15, 2026

Status verified date

Sep, 2026

Completion date

Jan, 2029

Anticipated

Primary completion date

Jan, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion

  • Age ≥18 years at the time of the emergency department visit.
  • Presentation to a participating emergency department following a traumatic injury mechanism (motor vehicle collision, fall from height, assault, head injury/head trauma/head strike, struck by or against an object, facial injury or laceration, or other general trauma). Presentations may also include alcohol intoxication or syncope when associated with a suspected traumatic brain injury.
  • Evidence of potential head or brain injury, defined as (i) the head being struck by an object, (ii) the head striking a hard object or surface, (iii) exposure of the brain to significant acceleration/deceleration forces, or (iv) clinician documentation that the patient was evaluated for suspected traumatic brain injury.
  • Glasgow Coma Scale (GCS) score of 13-15 at presentation.
  • Presentation to the emergency department within 24 hours of injury.

Exclusion Criteria:

  • Planned computed tomography (CT) imaging of the maxillofacial bones, chest, abdomen, or pelvis during the ED encounter AND clinicians do not intend to avoid brain CT imaging even if the biomarker test is negative.
  • Current use of anticoagulant or antiplatelet therapy, including but not limited to: Warfarin, Factor Xa inhibitors (e.g., apixaban \[Eliquis\], rivaroxaban \[Xarelto\]), Clopidogrel, Ticagrelor.
  • Presentation >24 hours after injury, due to the declining diagnostic sensitivity of Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin Carboxy-terminal Hydrolase L1 (UCH-L1) beyond this time window.

Study Design

Enrollment

3000 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Health Services Research

Interventions and Outcome Measures

Arms

active comparator: Clinical Pathway 2: Clinical Guidelines Only

Clinical Guidelines Only (Canadian CT Head Rule)

experimental: Clinical Pathway 1: Guidelines + Biomarkers

Canadian CT Head Rule plus whole blood Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin Carboxy-Terminal Hydrolase L1 (UCH-L1) measurement using the i-STAT.

Interventions

Clinical pathway 1: Guidelines plus biomarkers

Patients will be managed using an algorithm that integrates the Canadian CT Head Rule (CCHR) with i-STAT whole-blood GFAP and UCH-L1 testing. Patients who meet CCHR criteria for CT imaging and those whose CT imaging decision-making is not covered by CCHR (e.g., no loss of consciousness or amnesia) will receive i-STAT testing. Sites will be assigned to one of three implementation waves, with two sites transitioning to the Guidelines + Biomarkers phase every six months. Prior to their assigned transition, sites will continue to use guidelines alone. Once a site transitions to the Guidelines + Biomarkers phase, the integrated biomarker-guided algorithm will become the standard-of-care protocol at that site for eligible patients and will remain the standard of care for the remainder of the study.

Clinical guidelines only

During the baseline phase, sites will rely solely on established clinical guidelines to guide brain CT utilization in patients with suspected TBI. Specifically, providers will apply the Canadian CT Head Rule, a validated decision instrument that identifies patients at high risk for clinically important brain injury who require CT imaging. All sites will begin in this Guidelines-Only baseline phase and will continue using this approach until their assigned transition to the Guidelines + Biomarkers phase. Sites will transition in three waves, with two sites transitioning every six months.

Primary outcome measure

  • The proportion of eligible emergency department (ED) patients with suspected traumatic brain injury (TBI) who receive brain CT imaging. [ Time Frame: Initial Emergency Department Visit (approximately 24 hours) ]

Central Contacts and Locations

Central contacts

Devon Newman, MS

734-652-9679devonn@med.umich.edu

Locations

UCLA-Olive View Medical Center

Recruiting

Sylmar, California, United States, 91342

Contacts

Yesenia Perez

YPerez@dhs.lacounty.gov

Principal Investigator:

Breena Taira, MD, MPH

Harbor-UCLA Medical Center

Recruiting

Torrance, California, United States, 90502

Contacts

Evelyn Santana

424-306-5400evelyn.santana@lundquist.org

Principal Investigator:

Kabir Yadav, MD, MS, MHSH

Henry Ford Macomb (HFM)

Recruiting

Clinton Township, Michigan, United States, 48038

Contacts

Jo-Ann Rammal

313-404-9110JRammal1@hfhs.org

Principal Investigator:

Joseph Miller, MD, MS

Henry Ford Hospital (HFH)

Recruiting

Detroit, Michigan, United States, 48202

Contacts

Jo-Ann Rammal

313-404-9110JRammal1@hfhs.org

Principal Investigator:

Joseph Miller, MD, MS

Hillsboro Medical Center

Recruiting

Portland, Oregon, United States, 97216

Contacts

Maja Strusinska-Thayer

503-418-2713strusins@ohsu.edu

Principal Investigator:

Bory Kea, MD, MCR

Oregon Health & Science University (OHSU)

Recruiting

Portland, Oregon, United States, 97239

Contacts

Maja Strusinska-Thayer

503-418-2713strusins@ohsu.edu

Principal Investigator:

Bory Kea, MD, MCR

More Information

Sponsor

University of Michigan

Last update posted

Nov 10, 2026

Last verified

Sep, 2026

Keywords

  • Emergency department
  • Struck by or against an object
  • traumatic brain injury
  • TBI
  • CT imaging
  • head CT
  • brain CT
  • biomarkers
  • clinical decision rule
  • implementation study
  • gfap
  • UCH-L1
  • glial fibrillary acidic protein
  • Ubiquitin Carboxy-terminal hydrolase L1

Trial information was received from ClinicalTrials.gov and was last updated on 2026-11-11. This information was provided to ClinicalTrials.gov by University of Michigan on 2026-11-10. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.