Baseline results | Tranexamic acid to reduce head injury death in people with traumatic brain injury: the CRASH-3 international RCT

Tranexamic acid to reduce head injury death in people with traumatic brain injury: the CRASH-3 international RCT · Baseline results

Baseline results

The first patient was randomised on 20 July 2012 and the last patient on 31 January 2019. Recruitment ended when the trial treatment expired.

Figure 1 shows the trial profile. A total of 12,737 patients were randomly allocated to receive TXA (6406 patients) or matching placebo (6331 patients). A total of 9202 patients were enrolled within 3 hours of injury. Forty patients withdrew consent after randomisation, but 13 of them agreed to outcome data collection or had outcome data collected as part of adverse event reporting. We did not obtain primary outcome data for 75 patients (0.8%). There were 98 protocol violations. Sixty-six patients did not meet the inclusion criteria (32 patients had a GCS score of > 12 and no bleeding on CT scan, 11 had significant extracranial bleeding, eight had a time since injury of > 8 hours, six were aged < 16 years, three had non-traumatic bleeding, five had a combination of the above reasons, and one patient received TXA before randomisation). Thirty-two patients were recruited during a lapse in ethics approval in country. These patients were recruited in accordance with the approved procedure and approval was reissued after the lapse. Thirteen patients were unblinded. Baseline characteristics were similar between treatment groups for patients treated within 3 hours of injury (Table 1) and for those treated after 3 hours (Table 2).

FIGURE 1 Trial profile. (Figure not reproduced here; see the original article.)

TABLE 1 Baseline characteristics in participants randomised within 3 hours of injury

	TXA (N = 4649), n	%	Placebo (N = 4553), n	%
Sex
Male	3742	80	3660	80
Female	906	19	893	20
Unknown	1	< 1	0	0
Age (years)
Mean (SD)	41.7	19.0	41.9	19.0
< 25	1042	22	996	22
25–44	1716	37	1672	37
45–64	1169	25	1184	26
≥ 65	722	16	701	15
Time since injury (hours)
Mean (SD)	1.9	0.7	1.9	0.7
≤ 1	877	19	869	19
> 1–2	2003	43	1889	41
> 2–3	1769	38	1795	39
SBP (mmHg)
< 90	89	2	85	2
90–119	1508	32	1490	33
120–139	1461	31	1504	33
≥ 140	1576	34	1466	32
Unknown	15	< 1	8	< 1
GCS scorea
3	495	11	506	11
4	213	5	213	5
5	163	4	172	4
6	221	5	232	5
7	311	7	294	6
8	354	8	315	7
9	335	7	292	6
10	371	8	364	8
11	375	8	390	9
12	476	10	478	10
13	297	6	312	7
14	526	11	458	10
15	484	10	492	11
Unknown	28	1	35	1
Pupil reaction
None react	425	9	440	10
One reacts	374	8	353	8
Both react	3706	80	3636	80
Unable to assess/unknown	144	3	124	3

TABLE 2 Baseline charactersitics before randomisations of all participants and participants randomised beyond 3 hours of injury

	All				> 3 hours
	TXA (N = 6406)		Placebo (N = 6331)		TXA (N = 1757)		Placebo (N = 1778)
	n	%	n	%	n	%	n	%
Sex
Male	5104	80	5013	79	1362	78	1353	76
Female	1301	20	1318	21	395	22	425	24
Unknown	1	< 1	0	0	0	0	0	0
Age (years)
Mean (SD)	43	19.8	43.1	19.7	46.4	21.3	46.2	21.1
< 25	1362	21	1326	21	320	18	330	19
25–44	2285	36	2264	36	569	32	592	33
45–64	1625	25	1613	25	456	26	429	24
≥ 65	1134	18	1128	18	412	23	427	24
Time since injury (hours)
Mean (SD)	2.9	3.2	2.9	2.3	5.5	5.2	5.4	2.9
≤ 1	877	14	869	14	–	–	–	–
1–3	3772	59	3684	58	–	–	–	–
3–8	1737	27	1760	28	1737	99	1760	99
> 8	20	< 1	18	< 1	20	1	18	1
SBP (mmHg)
< 90	108	2	109	2	19	1	24	1
90–119	2001	31	1988	31	493	28	498	28
120–139	2107	33	2120	33	646	37	616	35
≥ 140	2167	34	2097	33	591	34	631	35
Unknown	23	< 1	17	< 1	8	< 1	9	1
GCS scorea
3	630	10	642	10	135	3	136	3
4	261	4	275	4	48	1	62	1
5	211	3	242	4	48	1	70	2
6	304	5	308	5	83	2	76	2
7	413	6	400	6	102	2	106	2
8	465	7	406	6	111	2	91	2
9	416	6	382	6	81	2	90	2
10	463	7	444	7	92	2	80	2
11	465	7	502	8	90	2	112	2
12	600	9	601	9	124	3	123	3
13	460	7	453	7	163	4	141	3
14	790	12	754	12	264	6	296	7
15	899	14	886	14	415	9	394	9
Unknown	29	< 1	36	1	1	< 1	1	< 1
Pupil reaction
None react	536	8	575	9	111	6	135	8
One reacts	511	8	482	8	137	8	129	7
Both react	5174	81	5113	81	1468	84	1477	83
Unable to assess/unknown	185	3	161	3	41	2	37

Attribution. Ian Roberts; Haleema Shakur-Still; Amy Aeron-Thomas; Danielle Beaumont; Antonio Belli; Amy Brenner et al. (2021). Tranexamic acid to reduce head injury death in people with traumatic brain injury: the CRASH-3 international RCT. NIHR Journals Library. Copyright © 2021 Roberts et al. This work was produced by Roberts et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This is an Open Access publication distributed under the terms of the Creative Commons Attribution CC BY 4.0 licence, which permits unrestricted use, distribution, reproduction and adaption in any medium and for any purpose provided that it is properly attributed. See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source – NIHR Journals Library, and the DOI of the publication must be cited. Licensed under CC BY 4.0. NCBI Bookshelf NBK570193. CC BY 4.0. Original source ↗. Text reproduced from the Bookshelf XML without changing wording; figures, images and supplements are not reproduced.