Table 4. Adjusted Analyses of Select Secondary Outcomes and Adverse Events in a Study of the Effect of Tranexamic Acid vs Placebo on Neurologic Outcomes in Patients With Traumatic Brain Injury.
| Outcome | Treatment group, No. (%)a | Adjusted difference (95% CI)b | |||||
|---|---|---|---|---|---|---|---|
| Bolus maintenance | Bolus only | Placebo | Bolus maintenance vs placebo | Bolus only vs placebo | Bolus only vs bolus maintenance | ||
| Secondary outcomes (exploratory) | (n = 312) | (n = 345) | (n = 309) | ||||
| 6-mo Glasgow Outcome Scale-Extended score >4c | 198 (63) | 226 (66) | 192 (62) | 2.0 (−5.8 to 9.8) | 4.8 (−2.9 to 12.5) | 2.8 (−4.6 to 10.2) | |
| 28-d mortalityc | 53 (17) | 41 (12) | 53 (17) | −0.09 (−6.1 to 5.9) | −5.4 (−10.9 to 0.05) | −5.3 (−10.8 to 0.1) | |
| 6-mo Disability Rating Scale score, median (IQR)c | 2 (0 to 7) | 1 (0 to 5) | 1 (0 to 8) | −0.2 (−2.1 to 1.7) | −1.5 (−3.3 to 0.3) | −1.4 (−3.1 to 0.4) | |
| Progression of intracranial hemorrhaged,e | 26 (17) (n = 154) | 27 (15) (n = 178) | 30 (20) (n = 148) | −4.2 (−13.0 to 4.6) | −6.3 (−14.4 to 1.7) | −2.2 (−9.9 to 5.6) | |
| Adverse eventsf | (n = 312) | (n = 345) | (n = 309) | ||||
| Seizure/seizure-like activityc | 5 (2) | 17 (5) | 7 (2) | −0.6 (−2.8 to 1.6) | 2.8 (−0.1 to 5.6) | 3.4 (0.7 to 6.1) | |
| Any thromboembolic eventc | 13 (4) | 31 (9) | 30 (10) | −5.8 (−9.8 to −1.8) | −1.0 (−5.4 to 3.4) | 4.8 (1.1 to 8.5) | |
| Other adverse eventsc,g | 77 (25) | 79 (23) | 76 (25) | −0.4 (−7.1 to 6.2) | −2.3 (−8.8 to 4.3) | −1.8 (−8.3 to 4.6) | |
| Subgroups (exploratory) | |||||||
| Unimputed outcomesh | |||||||
| 6-mo Glasgow Outcome Scale-Extended score >4e | 153 (59) (n = 261) | 178 (62) (n = 288) | 163 (60) (n = 270) | 0.3 (−6.4 to 7.1) | 3.6 (−3.3 to 10.5) | 3.3 (−3.6 to 10.2) | |
| 28-d mortalitye | 53/307 (17) (n = 307) | 40 (12) (n = 336) | 50 (17) (n = 297) | 0.9 (−4.1 to 6.0) | −4.0 (−8.8 to 0.7) | −4.9 (−9.6 to −0.2) | |
| 6-mo Disability Rating Scale score, median (IQR)e | 2 (0 to 8) (n = 261) | 2 (0 to 5) (n = 287) | 1 (0 to 11) (n = 266) | −0.2 (−1.8 to 1.4) | −1.5 (−3.1 to 0.005) | −1.3 (−2.8 to 0.3) | |
| Intracranial hemorrhage on initial computed tomographic imagingi | (n = 177) | (n = 197) | (n = 171) | ||||
| 6-mo Glasgow Outcome Scale-Extended score >4e | 83 (47) | 108 (55) | 86 (50) | −3.9 (−13.0 to 5.2) | 4.8 (−4.4 to 14.0) | 8.7 (−0.3 to 17.8) | |
| 28-d mortalitye | 45 (26) | 35 (18) | 47 (27) | 0.8 (−7.0 to 8.7) | −8.2 (−15.6 to −0.8) | −9.0 (−16.1 to −1.8) | |
| 6-mo Disability Rating Scale score, median (IQR)e | 2 (0 to 30) | 2 (0 to 11) | 4 (0 to 30) | −0.06 (−2.3 to 2.1) | −2.2 (−4.3 to −0.1) | −2.2 (−4.2 to −0.08) | |
See Table 2 for descriptions of the Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS). Imputed outcomes are included for GOSE, DRS, and mortality. There were 20 imputed data sets generated, and the mean over both the participants and the 20 data sets is reported. Although mean “counts” are rounded to the nearest integer, each participant's mean over 20 imputed data sets may be fractional.
All outcomes are modeled with linear regression with robust standard errors. Adjustments for each model are included in footnotes. eTable 5 in Supplement 2 includes logistic regression results for binary outcomes.
Model adjusts for regional site only.
To analyze for progression of intracranial hemorrhage (ICH), an initial computed tomographic imaging volume had to be available as well as at least 1 subsequent computed tomographic imaging volume prior to evacuation of a hematoma (eTable 14 in Supplement 2). Progression is defined by a 33% increase or more in combined amount of epidural, subdural, and intraparenchymal hemorrhage volumes on a subsequent computed tomographic image relative to the initial computed tomographic image. The volume difference must be at least 1 mL.
Model adjusts for regional site, age, sex, penetrating vs blunt injury, out-of-hospital GCS, ISS, and AIS for the head region.
Counts are of participants with 1 or more events of the type listed in the row label.
Includes monitoring for the following events: cardiopulmonary resuscitation, cardiac arrest, cardiac failure, liver failure, acute kidney injury, kidney failure, acute respiratory distress syndrome, cerebral vasospasm, hemorrhagic cerebral vascular accident, central diabetes insipidus, hypernatremia, pseudomembranous colitis, abdominal compartment syndrome, extremity compartment syndrome, fat embolism, posterior ischemic optic neuropathy, anterior ischemic optic neuropathy, pneumonia, sepsis, bloodstream infection, urinary tract infection, meningitis, empyema, cholecystitis, intra-abdominal abscess, pseudomembranous colitis, wound infection, and osteomyelitis.
This section includes participants who completed the 6-month assessment for GOSE and DRS outcomes (ie, outcome was not imputed). For 28-day mortality, it includes participants for whom vital status at 28 days is definitively known and participants who were lost to follow-up prior to 28 days but who were notified of their study participation themselves rather than only family members being notified (n = 52).The latter were assumed to survive through 28 days. Participants are generally notified themselves only if they are sufficiently cognizant to receive and process such information. Among participants with definitive 28-day vital status who were notified themselves of the study only 1 of 362 died before day 28.
Participants with computed tomographic images from which the central reader could not determine whether there was a bleed or not were excluded from both the “Intracranial hemorrhage” and “No intracranial hemorrhage” groups, as were participants who died prior to receiving a computed tomographic image and there was no other evidence to determine whether the participant had an intracranial hemorrhage or not. Among the 26 participants not included in either subgroup, 14 died within 28 days (6 in the bolus maintenance group, 2 in the bolus only group, and 6 in the placebo group).