Multi-Arm Multi-Stage Adaptive Platform Trial (APT) for the Acute Treatment of Traumatic Brain Injury
APT-TBI-01
1 other identifier
interventional
672
1 country
18
Brief Summary
The purpose of this study is to determine if experimental drug treatment improves recovery after TBI as compared to a control (placebo) group. Changes in recovery will be measured throughout the study. The study drugs listed below are approved by the U.S. Food and Drug Administration (FDA) but are being used "off-label" in this study. This means that the drugs are not currently approved to treat TBI.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2024
Longer than P75 for phase_2
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 12, 2023
CompletedFirst Posted
Study publicly available on registry
April 24, 2023
CompletedStudy Start
First participant enrolled
August 1, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2029
December 22, 2025
December 1, 2025
4.1 years
April 12, 2023
December 18, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Change in Glasgow Outcome Scale-Extended (GOSE 2-Way)
Functional impairment due only to the TBI will be measured using the GOSE Scale-Extended (GOSE 2-Ways). The score ranges from 1-8, with higher scores indicating better recovery. Change will be measured from Week 2 to Month 3 postinjury and compared to placebo.
2 weeks to 3 months postinjury
Secondary Outcomes (5)
Change in Blood-based biomarkers (Neurofilament light chain)
Week 2
Blood-based biomarker (GFAP)
Week 2
Imaging biomarkers
2 weeks to 3 months postinjury
Post-TBI cognitive outcome (BTACT)
Day 3 to Week 4 postinjury
Post-TBI symptom outcome (Rivermead)
Day 3 to Week 4
Study Arms (4)
Intervention 1: Atorvastatin calcium (ATOR)
ACTIVE COMPARATORBy Mouth (PO) Twice a day (BID) 80 mg/day, with no loading dose, for 28 days
Intervention 2: Minocycline hydrochloride (MINO)
ACTIVE COMPARATORBy Mouth (PO) Twice a day (BID) 200 mg loading dose on Day 1, then 100 mg twice daily for 6 days, then placebo twice daily for 21 days
Intervention 3: Candesartan cilexetil (CAND)
ACTIVE COMPARATORBy Mouth (PO) Twice a day (BID) 8 mg once on Day 1, then 16 mg daily for 27 days
Matching Placebo
PLACEBO COMPARATORBy Mouth (PO) Twice a day (BID) 2 capsules 2x/day
Interventions
Capsule, 80 mg/day, with no loading dose, for 28 days
Capsule, 200 mg loading dose on Day 1, then 100 mg twice daily for 6 days, then placebo twice daily for 21 days
Capsule, 8 mg once on Day 1, then 16 mg daily for 27 days
Eligibility Criteria
You may qualify if:
- Adults (18-65 years of age, inclusive)
- Presents to a participating enrollment site and is able to receive first dose within 24 hours of non-penetrating head injury warranting clinical evaluation with a non-contrast head CT based on American College of Emergency Physicians (ACEP) Centers for Disease Control and Prevention (CDC) clinical policy for TBI imaging.
- Closest, prior to Randomization Glasgow Coma Scale (GCS) score of 9 to 15
- Acute trauma-related neuroimaging abnormality (subarachnoid hemorrhage, contusion, subdural hematoma, petechial hemorrhage, intraventricular hemorrhage) on cranial CT (CT+)
- Initial Glial Fibrillary Acidic Protein (GFAP) blood level \>100 pg/ml ≤ 15,000 pg/ml determined using a for Research Use Only (RUO) assay(s) or an Investigation Use Only (IUO) assay(s)
- Persons of childbearing potential (i.e., those not postmenopausal or surgically sterile) may participate provided that they are using adequate birth control methods for the duration of investigational product administration (see manual of procedures for adequate birth control methods)
- Participants able to undergo Magnetic Resonance Imaging (MRI) scans, no contraindications
- Participants or legally authorized representative (LAR) willing and able to provide informed consent
- Participants or LAR able to read, speak, and understand English or Spanish (participating site dependent, where available), including the informed consent form (ICF)
- Willingness and ability to comply with all study procedures, treatment, and follow-up
You may not qualify if:
- Isolated epidural hematoma
- Pre-existing conditions including disabling developmental, neurologic, psychiatric, medical disorder that continues to produce functional disability up to the time of injury; or imminent death based on clinical judgement
- Current enrollment in another interventional study
- Currently pregnant or currently breastfeeding or planning on becoming pregnant in the next 6 months
- Current incarceration or in custody
- Currently prescribed one of the investigational products (or other drugs in the same class) prior to injury; or contra-indicated or as listed in the appendices
- Hypersensitivity or intolerance to investigational products or the investigational products' respective classes
- Renal dysfunction (Creatinine Clearance (CrCl) or estimated Glomerular Filtration Rate (eGFR) (\<60 mL/minute/1.73 m2)
- Acute liver disease or hepatic dysfunction (ALT/AST \>3 times upper limit of normal lab value)
- Hemodynamic instability, per participating site physician investigator clinical judgment
- Inability to swallow investigational product capsule
- Unable or unwilling to consume animal byproducts, has a gelatin allergy, and/or religious beliefs that do not permit consuming gelatin
- Intolerance to small amounts of lactose (less than ½ teaspoonful) daily
- Low likelihood of follow up or study compliance, or any other reason, in the opinion of the participating site investigator, the participants should not participate in the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
University of California, San Francisco
San Francisco, California, 94110, United States
Indiana University Health
Indianapolis, Indiana, 46202, United States
University of Kentucky
Lexington, Kentucky, 40536, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Atrium Health Wake Forest Baptist
Charlotte, North Carolina, 28203, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37203, United States
The University of Texas at Austin
Austin, Texas, 78712, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
UTHealth Houston
Houston, Texas, 77030, United States
University of Utah
Salt Lake City, Utah, 84132, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
University of Washington
Seattle, Washington, 98104, United States
UW Health University Hospital
Madison, Wisconsin, 53792, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Geoffrey Manley, MD PhD
University of California, San Francisco
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 12, 2023
First Posted
April 24, 2023
Study Start
August 1, 2024
Primary Completion (Estimated)
August 31, 2028
Study Completion (Estimated)
August 31, 2029
Last Updated
December 22, 2025
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- Shared scientific data will be made accessible as soon as possible, and no later than the time of an associated publication, or the end of performance period, whichever comes first.
- Access Criteria
- FITBIR qualified investigators will be provided access
Data will be made available through the Federal Interagency TBI Research (FITBIR) Database.