Characteristics of the studies included in the systematic review and meta-analysis
| Variable | TRAIGE | STOP-AUST | SPOTLIGHT and STOP-IT | TICH-2 |
| Start time, y | 2015 | 2012 | 2010 | 2013 |
| Publication time, y | 2021 | 2020 | 2019 | 2018 |
| Location | 10 centres in China | 13 centres in Australia | 12 centres in Canada | 123 centres in 12 countries |
| Study type | mRCT | mRCT | mRCT | mRCT |
| Participant | Supratentorial ICH | Supratentorial ICH | Supratentorial ICH | ICH |
| CT signs | Spot sign, black hole sign, or blend sign | Spot sign only | Spot sign only | Data on CT sign were unavailable for subjects included in the overall analysis; spot sign in subgroup analysis; black hole sign and blend sign in post hoc analyses |
| Time (hour) | <6 | <4.5 | <6.5 | <8 |
| Number of patients in treatment group/ total for primary analysis | 89/172 | 50/100 | 32/69 | 1161/2325 in main overall analysis; 24/56 in spot sign subgroup; 411 in black hole sign subgroup; 364 in blend sign subgroup* |
| Age, mean±SD, y | 55.9±11.6 | 71 (IQR 57–79) | 70.7±13.7 | 66.7±12.4† | 68.9±13.8 |
| Male, n (%) | 124 (72.5) | 62 (62.0) | 35 (50.7) | 1301 (56.0) |
| Baseline NIHSS, median (IQR) | 11.0 (7.0–15.0) | NA | 16.0 (11.0–18.5) | 16.0 (13.0–20.0) | 13.1±7.5 | 12.9±7.5 |
| Hypertension, n (%) | 114 (66.7) | 69 (69.0) | 49 (71.0) | 1421 (61.1) |
| ICH volume, mean±SD, mL | 23.7±18.7 | 14.6 (IQR 7.9–32.7) | 16.3 (9.6–19.2) | 20.4 (8.6–32.6) | 24.0±27.2 |
| Intraventricular haemorrhage, n (%) | 33 (19.3) | 22 (22.0) | 28 (40.6) | 745 (32.0) |
| Spot sign, n (%) | 94 (55.0) | 100 (100.0) | 69 (100.0) | 56 (2.4) |
| Blend sign, n (%) | 47 (27.5) | NA | NA | 411 (17.7) |
| Black hole sign, n (%) | 107 (62.6) | NA | NA | 364 (15.7) |
| Onset to treatment, median (IQR), hour | 290 (185–370) | 150 (118–203) | 178 (138–197) | 246 (NA) |
| Randomisation | Randomised 1:1, double-blind, placebo-controlled | Randomised 1:1, double-blind, placebo-controlled | Randomised 1:1, double-blind, placebo-controlled | Randomised 1:1, double-blind, placebo-controlled |
| Intervention | Tranexamic acid: 1 g in 100 mL 0.9% NaCl over 10 min followed by 1 g in 250 mL 0.9% NaCl infusion over 8 hours | Tranexamic acid: 1 g in 100 mL 0.9% NaCl over 10 min followed by 1 g in 500 mL 0.9% NaCl infusion over 8 hours | rFVIIa: 80 µg/kg bolus | Tranexamic acid: 1 g in 100 mL 0.9% NaCl over 10 min followed by 1 g in 250 mL 0.9% NaCl infusion over 8 hours |
| Control | Placebo: saline | Placebo: saline | Placebo: saline | Placebo: saline |
| ITT | Yes | Yes | Yes | Yes |
| Primary outcome | HE 24 hours | HE 24 hours | HE 24 hours | mRS 90 days |
| Secondary outcome‡ | mRS 90 days, death | mRS 90 days, death | mRS 90 days, death | HE 24 hours, death |
| Follow-up | 90 days | 90 days | 90 days | 90 days |
Haemostatic therapy for preventing haematoma expansion.
*Numbers of subjects in the treatment group and the control group in the subgroups of TICH-2 were unavailable.
†a | b indicated data for the treatment group and the control group when data for total population were unavailable.
‡Details of other secondary outcomes of each included trial were listed in online supplemental 2.
HE, haematoma expansion; ICH, intracerebral haemorrhage; ITT, intention-to-treat analysis; mRCT, multicenter randomised controlled trial; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; rFVIIa, Recombinant factor VIIa;SPOTLIGHT, The“Spot Sign” Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy; STOP-AUST, the Spot sign and Tranexamic acid On Preventing ICH growth—AUStralasia Trial; STOP-IT, The Spot Sign for Predicting and Treating ICH Growth Study; TICH-2, Tranexamic acid for hyperacute primary intracerebral hemorrhage; TRAIGE, Tranexamic Acid for Acute ICH Growth prEdicted by Spot Sign.