The PIONEER Comparative Effectiveness Study - Project 2

September 14, 2026 updated by: Frederick Korley, MD, PhD, University of Michigan

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

3000

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Sylmar, California, United States, 91342
        • UCLA-Olive View Medical Center
        • Contact:
        • Principal Investigator:
          • Breena Taira, MD, MPH
      • Torrance, California, United States, 90502
        • Harbor-UCLA Medical Center
        • Contact:
        • Principal Investigator:
          • Kabir Yadav, MD, MS, MHSH
    • Michigan
      • Clinton Township, Michigan, United States, 48038
        • Henry Ford Macomb (HFM)
        • Contact:
        • Principal Investigator:
          • Joseph Miller, MD, MS
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital (HFH)
        • Contact:
        • Principal Investigator:
          • Joseph Miller, MD, MS
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University (OHSU)
        • Contact:
        • Principal Investigator:
          • Bory Kea, MD, MCR
      • Portland, Oregon, United States, 97216
        • Adventist Health Portland (AHP)
        • Contact:
        • Principal Investigator:
          • Bory Kea, MD, MCR

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Clinical Pathway 2: Clinical Guidelines Only
Clinical Guidelines Only (Canadian Head CT Decision Rule)
Diagnostic test: 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.
Experimental: Clinical Pathway 1: Guidelines + Biomarkers
Canadian Head CT Decision Rule plus whole blood Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin Carboxy-Terminal Hydrolase L1 (UCH-L1) measurement using the iSTAT.
Diagnostic test: Clinical pathway 1: Guidelines plus biomarkers
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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)
Initial Emergency room visit (approximately 24 hours)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Initial Emergency room visit (approximately 24 hours)
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
Within 7 days of the index/initial ED visit
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
Within 7 days of the index/initial ED visit
ED length of stay
Time Frame: Initial Emergency room visit (approximately 24 hours)
This will be measured in minutes.
Initial Emergency room visit (approximately 24 hours)
Initial and sustained provider adherence at 6 and 24 months post-implementation
Time Frame: 6 and 24 months post-implementation
6 and 24 months post-implementation
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.
During implementation phase (months 9-32)
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)
During implementation phase (months 9-32)
30-day ED revisits and hospitalizations
Time Frame: 30 days following Initial Emergency room visit
30 days following Initial Emergency room visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Collaborators

United States Department of Defense

Investigators

  • Principal Investigator: Frederick Korley, MD, PhD, University Of Michigan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

January 1, 2029

Study Completion (Estimated)

January 1, 2029

Study Registration Dates

First Submitted

September 14, 2026

First Submitted That Met QC Criteria

September 14, 2026

First Posted (Actual)

September 18, 2026

Study Record Updates

Last Update Posted (Actual)

September 18, 2026

Last Update Submitted That Met QC Criteria

September 14, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HUM00278426
  • HT942524TBIPHRPFPA (Other Identifier: Department of Defense)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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