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NCT Number: NCT07829107

The PIONEER Comparative Effectiveness Study - Project 2

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 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.

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Key information

Conditions

Head Injury Trauma Brain Concussion Brain Diseases Brain Injuries Brain Injuries, Traumatic Central Nervous System Diseases Craniocerebral Trauma Disease Attributes Emergencies Head Injuries, Closed Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Trauma, Nervous System Traumatic Brain Injury, Mild Wounds and Injuries Wounds, Nonpenetrating

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

UCLA-Olive View Medical Center, Sylmar, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 Carboxy-terminal Hydrolase L1 (UCH-L1) beyond this time window.

Treatment and study plan

Clinical pathway 1: Guidelines plus biomarkers

Diagnostic Test

Patients will be managed using an algorithm that integrates the Canadian Head CT Rule (CHCR) with iSTAT whole-blood GFAP and UCH-L1 testing. Patients who meet CHCR criteria for CT imaging and those whose CT imaging decision-making is not covered by CHCR (e.g., no loss of consciousness or amnesia) will receive iSTAT 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

Diagnostic Test

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 outcomes

  1. The proportion of eligible Emergency department (ED) patients with suspected traumatic brain injury (TBI) who receive brain CT imaging.

    Time frame: Initial Emergency room visit (approximately 24 hours)

Secondary outcomes

  1. Proportion of eligible ED patients with suspected TBI who receive brain CT imaging and have a clinically significant traumatic lesion.

    Time frame: Initial Emergency room visit (approximately 24 hours)

  2. Incidence of clinically significant missed traumatic intracranial injury diagnosed within 7 days of the index ED visit

    Time frame: Within 7 days of the index/initial ED visit

  3. Incidence of Neurosurgical interventions within 7 days of the index ED visit, without a new traumatic event.

    Time frame: Within 7 days of the index/initial ED visit

  4. ED length of stay

    Time frame: Initial Emergency room visit (approximately 24 hours)

    This will be measured in minutes.

  5. Initial and sustained provider adherence at 6 and 24 months post-implementation

    Time frame: 6 and 24 months post-implementation

  6. Provider acceptability and feedback

    Time frame: During implementation phase (months 9-32)

    Providers will answer 17 questions regarding the implementation of the biomarker guided algorithm and acceptability. Information from this will be summarized.

  7. Provider trust in biomarker-guided CT decision making as measured by the proportion of biomarker-negative patients who don't get a CT

    Time frame: During implementation phase (months 9-32)

  8. 30-day ED revisits and hospitalizations

    Time frame: 30 days following Initial Emergency room visit

Study contacts

Contact information is provided by the study sponsor or research team.

Devon Newman, MS

CONTACT

[email protected]

734-652-9679

Sponsors and collaborators

Lead sponsor

University of Michigan

Other

Collaborators

  • United States Department of Defense

Registry information

Official study title

Comparing the Effectiveness of a Biomarker-plus-clinical Guidelines Algorithm Versus Clinical Guidelines Only for Safely Decreasing Brain Computed Tomography Utilization During Brain Injury Evaluations: The PIONEER Comparative Effectiveness Study

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Sep 18, 2026
Registry last updated
Sep 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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