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Randomized Controlled Trial
. 2024 Jun 25;102(12):e209169.
doi: 10.1212/WNL.0000000000209169. Epub 2024 May 24.

Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage

Maud A Tjerkstra  1 , René Post  1 , Menno R Germans  1 , Mervyn D I Vergouwen  1 , Korne Jellema  1 , Radboud W Koot  1 , Nyika D Kruyt  1 , Jasper F C Wolfs  1 , Frits C De Beer  1 , Hans H Kieft  1 , Dharmin Nanda  1 , Bram Van Der Pol  1 , Gerwin Roks  1 , Frank De Beer  1 , Loes J A Reichman  1 , Paul J A M Brouwers  1 , Vincent I H Kwa  1 , Taco C Van Der Ree  1 , Henri P Bienfait  1 , Hieronymus D Boogaarts  1 , Catharina J Klijn  1 , Victoria Visser  1 , René van den Berg  1 , Bert A Coert  1 , Janneke Horn  1 , Charles B L M Majoie  1 , Gabriël J E Rinkel  1 , Yvo B W E M Roos  1 , W Peter Vandertop  1 , Dagmar Verbaan  1 ; ULTRA trial study group  1
Affiliations
Randomized Controlled Trial

Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage

Maud A Tjerkstra et al. Neurology. .

Abstract

Background and objectives: The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH.

Methods: The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade (p = 0.10).

Results: Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56).

Discussion: This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care.

Trial registration information: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013).

Classification of evidence: This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.

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Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: M.D.I. Vergouwen reports a grant from the Dutch Heart Foundation (Clinical Established Investigator grant 2018T076); J.F.C. Wolfs reports personal fees from Consultant Nuvasive, personal fees from Zimmer Biomet, personal fees from Safe Orthopaedics, and personal fees from EIT/Johnson and Johnson, outside the submitted work; H.D. Boogaarts reports consulting fees paid to the Department of Neurosurgery, Radboud University Medical Center Nijmegen from Stryker neurovascular; R. van den Berg reports consulting fees for unrelated research and teaching activities from Cerenovus Neurovascular; C.B.L.M. Majoie reports grants from CVON/Dutch Heart Foundation, grants from European Commission, grants from Dutch Health Evaluation Program, grants from TWIN Foundation, and grants from Stryker, outside the submitted work and is a Shareholder of Nico-Lab, a company that focuses on the use of artificial intelligence for medical image analysis; G.J.E. Rinkel reports no disclosures relevant to the manuscript; Y.B.W.E.M. Roos is a minor stockholder of Nico-Lab; D. Verbaan reports funding of Fonds NutsOhra; the other authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.

Figures

Figure 1
Figure 1. Flow Diagram of Included Patients
Figure 2
Figure 2. Distribution of Modified Rankin Scale Score at 6 Months in Both Treatment Groups, Separately Analyzed for Patients With Good-Grade and Poor-Grade aSAH, Using the As-Treated Principle
Stacked bar chart of scores on the modified Rankin scale (0–6). A score of 0 indicates no symptoms, 1 no clinically significant disability, 2 slight disability (patient is able to look after own affairs without assistance, but is unable to perform all previous activities), 3 moderate disability (patient requires some help but is able to walk unassisted), 4 moderately severe disability (patient is unable to attend to bodily needs without assistance and unable to walk unassisted), 5 severe disability (patient requires constant nursing care and attention), and 6 death. In good-grade patients, the overall distribution of the mRS scores 6 months after aSAH with ordinal regression analysis differed significantly between the TXA and usual care groups, showing worse mRS scores in the TXA group (OR 0.67, 95% CI 0.48–0.94; aOR 0.68, 95% CI 0.48–0.94, adjusted for treatment center). In poor-grade patients, the overall distribution of mRS scores 6 months after aSAH with ordinal regression analysis showed no significant differences between the TXA and usual care groups, OR 1.04, 95% CI 0.70–1.55, neither after adjustment for treatment center, aOR 1.05, 95% CI 0.70–1.56. aSAH = aneurysmal subarachnoid hemorrhage; mRS = modified Rankin scale; TXA = tranexamic acid.
See this image and copyright information in PMC

References

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