Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post Hoc Analysis of the ULTRA Trial

Maud A Tjerkstra¹, René Post², Menno R Germans², Mervyn D I Vergouwen², Korné Jellema², Radboud W Koot², Nyika D Kruyt², Peter W A Willems², Jasper F C Wolfs², Frits C de Beer², Hans Kieft², Dharmin Nanda², Bram van der Pol², Gerwin Roks², Frank de Beer², Patricia H A Halkes², Loes J A Reichman², Paul J A M Brouwers², Renske M Van den Berg-Vos², Vincent I H Kwa², Taco C van der Ree², Irene Bronner², Henri P Bienfait², Hieronymus Boogaarts², Catharina J M Klijn², René van den Berg², Bert A Coert², Janneke Horn², Charles B L M Majoie², Gabriël J E Rinkel², Yvo B W M Roos², W Peter Vandertop², Dagmar Verbaan²; ULTRA investigators

Collaborators, Affiliations

Affiliations

¹ From the Department of Neurosurgery (M.A.T., R.P., B.A.C., W.V., D.V.), Amsterdam Neuroscience Research Institute, Amsterdam University Medical Centres, the Netherlands; Department of Neurosurgery (M.R.G.), Clinical Neuroscience Centre, University Hospital Zurich, Switzerland; Department of Neurology and Neurosurgery (M.D.I.V., P.W.A.W., G.J.E.R.), UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht University; Department of Neurology (K.J.), Haaglanden Medical Centre, the Hague; Department of Neurosurgery (R.W.K.), Leids University Medical Centre; Department of Neurology (N.D.K.), Leids University Medical Centre; Department of Neurosurgery (J.F.C.W.), Haaglanden Medical Centre, the Hague; Department of Neurosurgery (F.C.B., D.N.), Isala Hospital, Zwolle; Department of Intensive Care (H.K.), Isala Hospital, Zwolle; Department of Neurosurgery (B.P.), Elisabeth Tweesteden Ziekenhuis, Tilburg; Department of Neurology (G.R.), Elisabeth Tweesteden Ziekenhuis, Tilburg; Department of Neurology (F.B.), Spaarne Gasthuis, Haarlem; Department of Neurology (P.H.A.H.), Noordwest Ziekenhuisgroep, Alkmaar; Department of Neurology (L.J.A.R.), Ziekenhuisgroep Twente, Almelo; Department of Neurology (P.J.A.M.B.), Medisch Spectrum Twente, Enschede; Department of Neurology (R.M.V.B.-V., V.I.H.K.), OLVG, Amsterdam; Department of Neurology (R.M.V.B.-V., Y.B.W.M.R.), Amsterdam University Medical Centres, Llocation AMC; Department of Neurology (T.C.R.), Dijklander Hospital, Hoorn; Department of Neurology (I.B.), Flevo Hospital, Almere; Department of Neurology (H.P.B.), Gelre Hospital, Apeldoorn; Department of Neurosurgery (H.B.), Radboud University Medical Centre, Nijmegen; Department of Neurology (C.J.M.K.), Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen; Department of Radiology and Nuclear Medicine (R.B., C.B.L.M.M.), Amsterdam University Medical Centres, Location AMC; and Department of Intensive Care (J.H.), Amsterdam University Medical Centres, Location AMC, the Netherlands. m.a.tjerkstra@amsterdamumc.nl.
² From the Department of Neurosurgery (M.A.T., R.P., B.A.C., W.V., D.V.), Amsterdam Neuroscience Research Institute, Amsterdam University Medical Centres, the Netherlands; Department of Neurosurgery (M.R.G.), Clinical Neuroscience Centre, University Hospital Zurich, Switzerland; Department of Neurology and Neurosurgery (M.D.I.V., P.W.A.W., G.J.E.R.), UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht University; Department of Neurology (K.J.), Haaglanden Medical Centre, the Hague; Department of Neurosurgery (R.W.K.), Leids University Medical Centre; Department of Neurology (N.D.K.), Leids University Medical Centre; Department of Neurosurgery (J.F.C.W.), Haaglanden Medical Centre, the Hague; Department of Neurosurgery (F.C.B., D.N.), Isala Hospital, Zwolle; Department of Intensive Care (H.K.), Isala Hospital, Zwolle; Department of Neurosurgery (B.P.), Elisabeth Tweesteden Ziekenhuis, Tilburg; Department of Neurology (G.R.), Elisabeth Tweesteden Ziekenhuis, Tilburg; Department of Neurology (F.B.), Spaarne Gasthuis, Haarlem; Department of Neurology (P.H.A.H.), Noordwest Ziekenhuisgroep, Alkmaar; Department of Neurology (L.J.A.R.), Ziekenhuisgroep Twente, Almelo; Department of Neurology (P.J.A.M.B.), Medisch Spectrum Twente, Enschede; Department of Neurology (R.M.V.B.-V., V.I.H.K.), OLVG, Amsterdam; Department of Neurology (R.M.V.B.-V., Y.B.W.M.R.), Amsterdam University Medical Centres, Llocation AMC; Department of Neurology (T.C.R.), Dijklander Hospital, Hoorn; Department of Neurology (I.B.), Flevo Hospital, Almere; Department of Neurology (H.P.B.), Gelre Hospital, Apeldoorn; Department of Neurosurgery (H.B.), Radboud University Medical Centre, Nijmegen; Department of Neurology (C.J.M.K.), Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen; Department of Radiology and Nuclear Medicine (R.B., C.B.L.M.M.), Amsterdam University Medical Centres, Location AMC; and Department of Intensive Care (J.H.), Amsterdam University Medical Centres, Location AMC, the Netherlands.

PMID: 36266046
DOI: 10.1212/WNL.0000000000201160

Randomized Controlled Trial

Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post Hoc Analysis of the ULTRA Trial

Maud A Tjerkstra et al. Neurology. 2022.

. 2022 Dec 5;99(23):e2605-e2614.

doi: 10.1212/WNL.0000000000201160.

Authors

Affiliations

¹ From the Department of Neurosurgery (M.A.T., R.P., B.A.C., W.V., D.V.), Amsterdam Neuroscience Research Institute, Amsterdam University Medical Centres, the Netherlands; Department of Neurosurgery (M.R.G.), Clinical Neuroscience Centre, University Hospital Zurich, Switzerland; Department of Neurology and Neurosurgery (M.D.I.V., P.W.A.W., G.J.E.R.), UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht University; Department of Neurology (K.J.), Haaglanden Medical Centre, the Hague; Department of Neurosurgery (R.W.K.), Leids University Medical Centre; Department of Neurology (N.D.K.), Leids University Medical Centre; Department of Neurosurgery (J.F.C.W.), Haaglanden Medical Centre, the Hague; Department of Neurosurgery (F.C.B., D.N.), Isala Hospital, Zwolle; Department of Intensive Care (H.K.), Isala Hospital, Zwolle; Department of Neurosurgery (B.P.), Elisabeth Tweesteden Ziekenhuis, Tilburg; Department of Neurology (G.R.), Elisabeth Tweesteden Ziekenhuis, Tilburg; Department of Neurology (F.B.), Spaarne Gasthuis, Haarlem; Department of Neurology (P.H.A.H.), Noordwest Ziekenhuisgroep, Alkmaar; Department of Neurology (L.J.A.R.), Ziekenhuisgroep Twente, Almelo; Department of Neurology (P.J.A.M.B.), Medisch Spectrum Twente, Enschede; Department of Neurology (R.M.V.B.-V., V.I.H.K.), OLVG, Amsterdam; Department of Neurology (R.M.V.B.-V., Y.B.W.M.R.), Amsterdam University Medical Centres, Llocation AMC; Department of Neurology (T.C.R.), Dijklander Hospital, Hoorn; Department of Neurology (I.B.), Flevo Hospital, Almere; Department of Neurology (H.P.B.), Gelre Hospital, Apeldoorn; Department of Neurosurgery (H.B.), Radboud University Medical Centre, Nijmegen; Department of Neurology (C.J.M.K.), Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen; Department of Radiology and Nuclear Medicine (R.B., C.B.L.M.M.), Amsterdam University Medical Centres, Location AMC; and Department of Intensive Care (J.H.), Amsterdam University Medical Centres, Location AMC, the Netherlands. m.a.tjerkstra@amsterdamumc.nl.
² From the Department of Neurosurgery (M.A.T., R.P., B.A.C., W.V., D.V.), Amsterdam Neuroscience Research Institute, Amsterdam University Medical Centres, the Netherlands; Department of Neurosurgery (M.R.G.), Clinical Neuroscience Centre, University Hospital Zurich, Switzerland; Department of Neurology and Neurosurgery (M.D.I.V., P.W.A.W., G.J.E.R.), UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht University; Department of Neurology (K.J.), Haaglanden Medical Centre, the Hague; Department of Neurosurgery (R.W.K.), Leids University Medical Centre; Department of Neurology (N.D.K.), Leids University Medical Centre; Department of Neurosurgery (J.F.C.W.), Haaglanden Medical Centre, the Hague; Department of Neurosurgery (F.C.B., D.N.), Isala Hospital, Zwolle; Department of Intensive Care (H.K.), Isala Hospital, Zwolle; Department of Neurosurgery (B.P.), Elisabeth Tweesteden Ziekenhuis, Tilburg; Department of Neurology (G.R.), Elisabeth Tweesteden Ziekenhuis, Tilburg; Department of Neurology (F.B.), Spaarne Gasthuis, Haarlem; Department of Neurology (P.H.A.H.), Noordwest Ziekenhuisgroep, Alkmaar; Department of Neurology (L.J.A.R.), Ziekenhuisgroep Twente, Almelo; Department of Neurology (P.J.A.M.B.), Medisch Spectrum Twente, Enschede; Department of Neurology (R.M.V.B.-V., V.I.H.K.), OLVG, Amsterdam; Department of Neurology (R.M.V.B.-V., Y.B.W.M.R.), Amsterdam University Medical Centres, Llocation AMC; Department of Neurology (T.C.R.), Dijklander Hospital, Hoorn; Department of Neurology (I.B.), Flevo Hospital, Almere; Department of Neurology (H.P.B.), Gelre Hospital, Apeldoorn; Department of Neurosurgery (H.B.), Radboud University Medical Centre, Nijmegen; Department of Neurology (C.J.M.K.), Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen; Department of Radiology and Nuclear Medicine (R.B., C.B.L.M.M.), Amsterdam University Medical Centres, Location AMC; and Department of Intensive Care (J.H.), Amsterdam University Medical Centres, Location AMC, the Netherlands.

PMID: 36266046
DOI: 10.1212/WNL.0000000000201160

Abstract

Background and objectives: The ULTRA trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at 6 months. An expected proportion of the included patients experienced nonaneurysmal subarachnoid hemorrhage. In this post hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at 6 months.

Methods: The ULTRA trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013, and January 20, 2020. After confirmation of subarachnoid hemorrhage on noncontrast CT, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care or usual care only. In this post hoc analysis, we included all ULTRA participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin scale (mRS), dichotomized into good (0-3) and poor (4-6) outcomes.

Results: Of the 813 ULTRA trial patients who experienced an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio [aOR] 0.92; 95% CI 0.69-1.24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) (aOR 0.76; 95% CI 0.57-1.03), all-cause mortality at 30 days (aOR 0.91; 95% CI 0.65-1.28), and all-cause mortality at 6 months (aOR 1.10; 95% CI 0.80-1.52).

Discussion: Ultra-early and short-term tranexamic acid treatment did not improve clinical outcomes at 6 months in patients with aneurysmal subarachnoid hemorrhage and therefore cannot be recommended.

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 does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.

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Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post Hoc Analysis of the ULTRA Trial

Collaborators

Affiliations

Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post Hoc Analysis of the ULTRA Trial

Authors

Collaborators

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

Associated data