Table A1.
Summary of Clinical Trials.
| Reference | No. of Patients | Inclusion Criteria | Exclusion Criteria | TBI Severity | Time of Injury | Biomarkers |
|---|---|---|---|---|---|---|
| [62] | 109 | Military personnel and veterans | Psychosis; schizophrenia; schizoaffective disorder; bipolar disorder; contraindication to MRI scanning | All | Median 5 years | Serum tau, NFL, and amyloid-beta 40 and 42 |
| [63] | 98 | Military personnel deployed within the previous 18 months | Recent history of drug or alcohol abuse; current severe medical condition requiring long-term treatments; severe psychiatric conditions; severe neurological disorders | All | Most at least 18 months prior to the study | Plasma total tau |
| [68] | 155 | Patient in the ED of an adult level 1 trauma center; between 4 and 100 years old; had suspected head trauma requiring a head CT scan upon admission; available blood samples collected within 32 h of injury | Unidentified time of injury; history of head trauma 6 months prior to study; participating in another clinical study; active psychiatric, neurologic, and/or developmental disorders; admitted to the hospital’s special care unit; prisoners; persons in custody | All | 0–8 h and 12–32 h | Serum GFAP, UCH-L1, and S100B |
| [80] NCT01132898 |
91 | 18 years old or older; speak and write English; diagnosed with non-penetrating TBI; enrolled in study within 1 year of injury | Pregnancy; contraindication to MRI; history of significant psychiatric or neurologic conditions | All | 1 year | Extracellular vesicle GFAP and NFL |
| [81] | 488 | Service members and veterans; history of a TBI one year or more prior to study enrollment | Significant neurologic or psychiatric conditions | All | 1 year or more | Serum total tau, GFAP, NFL, and UCH-L1 |
| [82] | 230 | Subacute and chronic TBI patients; at least 18 years old; clinical diagnosis of nonpenetrating TBI; injury occurring within 1 year of enrollment | Contraindications to MRI; history of major neurologic or psychiatric conditions; pregnancy | All | 30 days to 5 years | Serum NFL, GFAP, UCH-L1, and tau |
| [83] | 343 | Patients with mTBI recruited from the emergency departments of a level 1 trauma center and an out-patient clinic | Not fluent in Norwegian; pre-existing neurological, psychiatric, somatic, or substance use disorder; history of complicated TBI; presence of other major interfering trauma; presentation more than 40 h after injury | mTBI | Acute to 12 months | Plasma NFL, GFAP and tau |
| [84] | 195 | History of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn deployment; history of combat exposure during any deployment; aged 18 years or older | History of moderate or severe TBI; history of major neurologic or psychiatric disorder | mTBI | Median 6.83–9.53 years | Exosomal and plasma NFL, TNF-alpha, IL-6, IL-10, and VEGF |
| [85] NCT01565551 |
107 | External force trauma to the head; presentation to the ED of a participating trauma center; a clinically indicated brain CT scan within 24 h of injury | Pregnancy; comorbid life-threatening disease; incarceration; on psychiatric hold; non-English speaking | All | Less than 24 h | Plasma GFAP, UCH-L1, NFL, and total tau |
| [86] | 21 | 18 years old or older; diagnosed with nonpenetrating moderate-to-severe TBI | Pregnancy; GCS equal to 3 associated with bilateral fixed and dilated pupils; normal head CT; interfering neurological comorbidities | moderate-severe TBI | up to 5 days | Serum exosomal GFAP, UCH-L1, NFL, and total tau |
| [87] NCT01565551 |
169 | Presented to a participating level 1 trauma center within 24 h of injury; received a head CT scan upon admission to trauma center; 16 years old or older; able to provide informed consent | non-English speaking; pregnant; in custody; undergoing psychiatric evaluation; contraindications to MRI; pre-existing interfering medical or neurological conditions | mTBI | Less than 24 h | Plasma p-tau, total tau, and GFAP |
| [88] | 584 | Adult trauma patients that presented to the ED of a level 1 trauma center within 4 h of injury | younger than 18 years old; no history of trauma as their primary event; had known dementia, chronic psychosis, or active central nervous system pathology; pregnant; incarcerated; had a systolic blood pressure less than 100 mm Hg. | mild moderate TBI | less than 4 h to 180 h | Serum GFAP and UCH-L1 |
| [89] NCT01990768 |
243 | Head trauma patients presenting in the ED of one of 20 trauma centers; blunt or penetrating TBI; moderate-to-severe TBI; prehospital systolic blood pressure greater than 90 mm Hg; prehospital intravenous access; 15 years or older (or weight 50 kg or more if age unknown); estimated time lapse of less than 2 h between injury and hospital arrival | Prehospital GCS of 3 with no reactive pupil; estimated time from injury to start of study of more than 2 h; unknown time of injury; clinical suspicion of seizure activity; acute MI or stroke; known history of confounding medical conditions; CPR by EMS prior to randomization; burns more than 20% TBSA; prisoners; pregnancy; prehospital pro-coagulant drug given prior to randomization; opting out of the study | mod-sev TBI | 0 to 24 h | Serum UCH-L1, GFAP, and MAP-2 |