Multi-Arm Multi-Stage Adaptive Platform Trial (APT) for the Acute Treatment of Traumatic Brain Injury (APT-TBI-01)

University of California San Francisco (UCSF)

Status and phase: Invitation-only; Phase 2

Conditions: Traumatic Brain Injury

Treatments: Drug: Atorvastatin Calcium; Drug: Candesartan Cilexetil; Drug: Minocycline Hydrochloride; Drug: Placebo

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT05826912

APT-TBI-01

Details and patient eligibility

About

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.

Enrollment: 672 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Adults (18-65 years of age, inclusive)
2. 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.
3. Closest, prior to Randomization Glasgow Coma Scale (GCS) score of 9 to 15
4. Acute trauma-related neuroimaging abnormality (subarachnoid hemorrhage, contusion, subdural hematoma, petechial hemorrhage, intraventricular hemorrhage) on cranial CT (CT+)
5. 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)
6. 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)
7. Participants able to undergo Magnetic Resonance Imaging (MRI) scans, no contraindications
8. Participants or legally authorized representative (LAR) willing and able to provide informed consent
9. Participants or LAR able to read, speak, and understand English or Spanish (participating site dependent, where available), including the informed consent form (ICF)
10. Willingness and ability to comply with all study procedures, treatment, and follow-up

Exclusion criteria

1. Isolated epidural hematoma
2. 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
3. Current enrollment in another interventional study
4. Currently pregnant or currently breastfeeding or planning on becoming pregnant in the next 6 months
5. Current incarceration or in custody
6. 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
7. Hypersensitivity or intolerance to investigational products or the investigational products' respective classes
8. Renal dysfunction (Creatinine Clearance (CrCl) or estimated Glomerular Filtration Rate (eGFR) (<60 mL/minute/1.73 m2)
9. Acute liver disease or hepatic dysfunction (ALT/AST >3 times upper limit of normal lab value)
10. Hemodynamic instability, per participating site physician investigator clinical judgment
11. Inability to swallow investigational product capsule
12. Unable or unwilling to consume animal byproducts, has a gelatin allergy, and/or religious beliefs that do not permit consuming gelatin
13. Intolerance to small amounts of lactose (less than ½ teaspoonful) daily
14. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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672 participants in 4 patient groups, including a placebo group

Intervention 1: Atorvastatin calcium (ATOR)

Active Comparator group

Description:

By Mouth (PO) Twice a day (BID) 80 mg/day, with no loading dose, for 28 days

Treatment:

Drug: Atorvastatin Calcium

Intervention 2: Minocycline hydrochloride (MINO)

Active Comparator group

Description:

By 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

Treatment:

Drug: Minocycline Hydrochloride

Intervention 3: Candesartan cilexetil (CAND)

Active Comparator group

Description:

By Mouth (PO) Twice a day (BID) 8 mg once on Day 1, then 16 mg daily for 27 days

Treatment:

Drug: Candesartan Cilexetil

Matching Placebo

Placebo Comparator group

Description:

By Mouth (PO) Twice a day (BID) 2 capsules 2x/day

Treatment:

Drug: Placebo