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

• Status: Not yet recruiting
• Trial end date: 2027-05-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborator: United States Department of Defense
• Treatments: Atorvastatin; Calcium; Candesartan; Candesartan cilexetil; Minocycline

Criteria

Inclusion Criteria:

1. Adults (18-65 years of age inclusive)

2. Presents to an enrollment site within 12 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. Post-resuscitation Glasgow Coma Scale (GCS) of between 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 the participant is 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 or need for sedation

8. Participants/legally authorized representative (LAR) willing and able to provide informed consent

9. Participants or legally authorized representative able to read, speak, understand English or Spanish including the informed consent form (ICF)

10. Willingness and ability to comply with all study procedures, treatment and follow-up

11. Participants identified by site investigator as a good candidate for study participation

Exclusion Criteria:

1. Post-resuscitation GCS <9

2. Isolated epidural hematoma

3. 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

4. Current enrollment in another interventional study

5. Currently pregnant or currently breastfeeding or planning on becoming pregnant in the next 6 months

6. Current incarceration

7. 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

8. Hypersensitivity or intolerance to investigational products or the investigational products respective classes

9. Renal dysfunction (Creatinine Clearance (CrCl) or Estimate Glomerular Filtration Rate (eGFR) <60 mL/minute/1.73 m2)

10. Hepatic dysfunction (ALT/AST >3 times upper limit of normal lab value)

11. Persistent hypotension, more than 30 minutes (Systolic Blood Pressure (SBP) <90 mmHg and Diastolic Blood Pressure (DBP) <60 mmHg)

12. Inability to swallow investigational product capsule

13. Low likelihood of follow up or study compliance, or any other reason, in the opinion of the site investigator, the participants should not participate in the study