Multi-institutional Phase 2/3 Trial of Valproic Acid in Patients with Moderate to Severe Traumatic Brain Injury (TBI)” or “VIBRANT-Valproic AcId for Traumatic BRAin INjury Trial” is a research study that will look at how valproic acid (a drug that was developed and approved to treat patients with seizures) given to traumatic brain injury patients soon after injury will affect their brain, and see if it will help in their injury recovery. This study uses an investigational treatment. “Investigational” means that valproic acid (VPA) as a treatment for traumatic brain injury is under investigation and is not approved for this use in the United States by the Food and Drug Administration (FDA). For this study, people who have traumatic brain injuries will be randomly picked to get either usual care, usual care + a low dose of VPA, or usual care + a high dose of VPA as part of their treatment at the hospital. Information from health records for the three groups will also be collected as part of the study. Researchers will look at the three groups of people and see if any group did better than the others. 

VIBRANT will enroll adults who are between 18 and 65 years old who are: 

• A Body Mass Index between 18 kg/m2 and 35 kg/m2 

• Females who are surgically sterilized, postmenopausal or who have a negative urine pregnancy test  

• Patients with a moderate to severe head injury, with a Glasgow Coma Scale (GCS) score between 3 and 12 (scale measures your eye, movement and verbal response) 
• Cerebral trauma confirmed on the initial CT scan with radiographic findings consistent with Brain Injury Guidelines category 3 (BIG3) criteria* 

Patients who meet any of the following criteria will be excluded: 

1. Persons with known history of adverse reaction to VPA. 
2. Persons with known history of hepatitis B or C or clinical history of hepatic dysfunction, pancreatitis, or renal insufficiency. 
3. Persons with a known history of thrombocytopenia. 
4. Persons with platelet count less than 100,000 per microliter of blood.
5. Persons with 2nd or 3rd degree burns of any size and location. 
6. Female subjects who are pregnant or lactating. 
7. Persons who are currently incarcerated or are in police custody. 
8. Persons with inadequate venous access. 
9. Treatment cannot start within 120 minutes from the onset of injury 
10. Non-survivable injuries in the estimation of the attending trauma surgeon. 
11. Interfacility transfers 
12. The time of injury is unknown 
13. Patients in hemorrhagic shock with a systolic blood pressure of <90 mmHg on initial evaluation.
14. Persons with a known “do not resuscitate” order prior to randomization 
15. Persons with a research “opt out” bracelet 
16. Persons who are currently enrolled in another clinical trial. 
17. Greater than 90 minutes between the onset of injury and arrival to the hospital 

*Joseph B, Obaid O, Dultz L, Black G, Campbell M, Berndtson AE, Costantini T, Kerwin A, Skarupa D, Burruss S, Delgado L, Gomez M, Mederos DR, Winfield R, Cullinane D; AAST BIG Multi-institutional Study Group. Validating the Brain Injury Guidelines: Results of an American Association for the Surgery of Trauma prospective multi-institutional trial. J Trauma Acute Care Surg. 2022 Aug 1;93(2):157-165. doi: 10.1097/TA.0000000000003554. Epub 2022 Mar 28. PMID: 35343931 

The study will take place at Northwestern University and at 8 other hospitals across the US. 

Previous studies in animals suggest that VPA to treat TBI can reduce brain damage, swelling, and help with long term brain function. 

VPA will be given one time as an intravenous (into a vein) infusion, which will begin within an hour of arriving in the emergency department. The treatment will be given in addition to usual care. No care will be withheld because of the research trial. 

VPA has been tested in previous studies and has been approved for use as treatment for epilepsy since 1978. Risks sometimes associated with VPA treatment include abdominal pain, headache, fatigue, drowsiness, nausea, sore throat, abdominal discomfort, changes in weight, low platelet count, and blurred vision. 

Risks and discomforts from study procedures 

• Blood draw: Pain, redness, soreness, bruising, or infection may occur at the needle stick site. 

• ECG: To measure your heart rate an electrocardiogram (ECG) will be done. This is a test that records the electrical activity of the heart. Sticky patches will be fixed to your chest as you lie down. You will be asked to lie still. The sticky pads used for the ECG may cause skin irritation. 

• Confidentiality: Any time information is collected there is a potential risk for loss of confidentiality. Every effort will be made to keep your information confidential; however, this cannot be guaranteed. This research study involves the use of your identifiable, personal information and there is a chance that a loss of confidentiality could occur. The researchers have procedures in place to decrease the possibility of this happening. 

Because this treatment is investigational, meaning non-FDA approved, there may be risks that we do not know about at this time. 

We are conducting this study because we anticipate that the benefits of getting VPA may include less injury or an increased chance of survival than if you had not received VPA. The additional study laboratory tests may provide information beneficial to you. The information that we obtain from this study may benefit others in the future and help us to provide more effective treatments for patients with traumatic brain injury in both the civilian and military populations. 

People who have traumatic brain injuries who are transported to a research site participating in VIBRANT may be included in this study. 

Normally, researchers must ask a person for their consent before they can be in a research study. Because traumatic brain injuries must be treated right away, there may not be time to get consent. Giving consent for medical research usually means reading information, talking with doctors and nurses, and having time to think about whether to join. A person with a traumatic brain injury is often not able to do these things. Sometimes researchers can talk to the patient’s family to ask for consent. However, in the emergency of a traumatic brain injury, the family is often not around or can’t be found before the injured person must be treated. This study could not be done without special permission to include people before getting consent. This permission is called Exception from Informed Consent, or EFIC. Once the enrolled person is better and can consent or their family arrives at the hospital, the researchers will ask for consent to continue with the study. For more information regarding EFIC, please 

visit: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/U CM249673.pdf]. 

You can opt-out of the study by contacting us using any of the methods below and letting us know that you do not want to participate. Please make sure to give us your name and contact information so that we can get in touch with you. We can provide you with a hypoallergenic silicone bracelet to wear that indicates that you should not be enrolled into the study. Please note that opting out of the study only means that you will not receive VPA as part of the study. Opting out will not prevent you from receiving normal care. 

For questions or to learn more about this study, please call us at 1-877–236–7487, email us at vibranttrial@northwestern.edu or complete the contact form below: