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BACKGROUND: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months.
METHODS: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812.
FINDINGS: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups.
INTERPRETATION: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale.
FUNDING: Fonds NutsOhra.
|Hemostasis and Thrombosis|
Nice trial with 2 areas that are worth considering: 1. Could we be seeing a Type II error here as there could be precision concerns and a signal for being under-powered? Is the case closed, or is more research needed given the low cost and safety? 2. Was ULTRA really that ultra-fast? Was delay to TXA a threat to external validity?
Despite its open-label design, this is a well done trial that was negative for effect of TXA in subarachnoid hemorrhage. This trial provides appropriate evidence to discourage the use of TXA in subarachnoid hemorrhage.
The result of this RCT indicated that ultra-early administration of tranexamic acid in patients with subarachnoid hemorrhage (median 185 minutes from onset of symptoms until diagnosis) did not improve the clinical outcome at 6 months. The administration of tranexamic acid for a series of hemorrhagic conditions seems to be in vogue these days. This study does not support its use in SAH.
This is as good as it gets for an open-label RCT.
This RCT of tranexamic acid (TXA) vs no TXA in spontaneous subarachnoid hemorrhage suggested no benefit of TXA. 50% of patients in the TXA arm did not finish the TXA dose because the need for surgical treatment of the aneurysm and because 15% expired. Thus, as a hematologist, I do not find this trial definitive. Reassuringly, there were no thrombotic events.
Tranexemic acid in subarachnoid hemorrhage is not a common practice. The neutral results do not change clinical practice much.
Although negative, this is an important trial.