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

Maud A. Tjerkstra; René Post; Menno R. Germans; Mervyn D.I. Vergouwen; Korné Jellema; Radboud W. Koot; Nyika D. Kruyt; Peter W.A. Willems; Jasper F.C. Wolfs; Frits C. De Beer; Hans Kieft; Dharmin Nanda; Bram Van Der Pol; Gerwin Roks; Frank De Beer; Patricia H.A. Halkes; Loes J.A. Reichman; Paul J.A.M. Brouwers; Renske M. Van Den Berg-Vos; Vincent I.H. Kwa; Taco C. Van Der Ree; Irene Bronner; Henri P. Bienfait; Hieronymus Boogaarts; Catharina J.M. Klijn; René Van Den Berg; Bert A. Coert; Janneke Horn; Charles B.L.M. Majoie; Gabriël J.E. Rinkel; Yvo B.W.M. Roos; W. Peter Vandertop; Dagmar Verbaan

doi:https://doi.org/10.1212/WNL.0000000000201160

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

Maud A. Tjerkstra, René Post, Menno R. Germans, Mervyn D.I. Vergouwen, Korné Jellema, Radboud W. Koot, Nyika D. Kruyt, Peter W.A. Willems, Jasper F.C. Wolfs, Frits C. De Beer, Hans Kieft, Dharmin Nanda, Bram Van Der Pol, Gerwin Roks, Frank De Beer, Patricia H.A. Halkes, Loes J.A. Reichman, Paul J.A.M. Brouwers, Renske M. Van Den Berg-Vos, Vincent I.H. KwaTaco C. Van Der Ree, Irene Bronner, Henri P. Bienfait, Hieronymus Boogaarts, Catharina J.M. Klijn, René Van Den Berg, Bert A. Coert, Janneke Horn, Charles B.L.M. Majoie, Gabriël J.E. Rinkel, Yvo B.W.M. Roos, W. Peter Vandertop, Dagmar Verbaan

Research output: Contribution to journal › Article › Academic › peer-review

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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 six months. An expected proportion of the included patients had non-aneurysmal 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 six 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 non-contrast computer tomography, 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 six months, assessed by the modified Rankin Scale, dichotomized into good (0-3) and poor (4-6) outcome.

Results: Of the 813 ULTRA-trial patients who had 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% confidence interval (C.I.) 0·69 to 1·24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) aOR 0.76, 95% C.I. 0.57-1.03, all-cause mortality at 30 days aOR 0.91, 95% C.I. 0.65-1.28), all-cause mortality at six months aOR 1.10 (95% C.I. 0.80-1.52).

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

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

Classification of evidence: This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.

Original language	English
Pages (from-to)	E2605-E2614
Journal	Neurology
Volume	99
Issue number	23
Early online date	20 Oct 2022
DOIs	https://doi.org/10.1212/WNL.0000000000201160
Publication status	Published - 20 Oct 2022

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Tjerkstra, M. A., Post, R., Germans, M. R., Vergouwen, M. D. I., Jellema, K., Koot, R. W., Kruyt, N. D., Willems, P. W. A., Wolfs, J. F. C., De Beer, F. C., Kieft, H., Nanda, D., Van Der Pol, B., Roks, G., De Beer, F., Halkes, P. H. A., Reichman, L. J. A., Brouwers, P. J. A. M., Van Den Berg-Vos, R. M., ... Verbaan, D. (2022). Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post-Hoc Analysis of the ULTRA Trial: Post-Hoc Analysis of the ULTRA Trial. Neurology, 99(23), E2605-E2614. https://doi.org/10.1212/WNL.0000000000201160

@article{ca9db059c3fb4388aa0824eeebebd46b,

title = "Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post-Hoc Analysis of the ULTRA Trial: Post-Hoc Analysis of the ULTRA Trial",

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 six months. An expected proportion of the included patients had non-aneurysmal 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 six 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 non-contrast computer tomography, 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 six months, assessed by the modified Rankin Scale, dichotomized into good (0-3) and poor (4-6) outcome.Results: Of the 813 ULTRA-trial patients who had 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% confidence interval (C.I.) 0·69 to 1·24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) aOR 0.76, 95% C.I. 0.57-1.03, all-cause mortality at 30 days aOR 0.91, 95% C.I. 0.65-1.28), all-cause mortality at six months aOR 1.10 (95% C.I. 0.80-1.52).Discussion: Ultra-early and short-term tranexamic acid treatment did not improve clinical outcome at six months in patients with aneurysmal subarachnoid hemorrhage and therefore, cannot be recommended.Trial registration: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24th, 2013).Classification of evidence: This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.",

author = "Tjerkstra, {Maud A.} and Ren{\'e} Post and Germans, {Menno R.} and Vergouwen, {Mervyn D.I.} and Korn{\'e} Jellema and Koot, {Radboud W.} and Kruyt, {Nyika D.} and Willems, {Peter W.A.} and Wolfs, {Jasper F.C.} and {De Beer}, {Frits C.} and Hans Kieft and Dharmin Nanda and {Van Der Pol}, Bram and Gerwin Roks and {De Beer}, Frank and Halkes, {Patricia H.A.} and Reichman, {Loes J.A.} and Brouwers, {Paul J.A.M.} and {Van Den Berg-Vos}, {Renske M.} and Kwa, {Vincent I.H.} and {Van Der Ree}, {Taco C.} and Irene Bronner and Bienfait, {Henri P.} and Hieronymus Boogaarts and Klijn, {Catharina J.M.} and {Van Den Berg}, Ren{\'e} and Coert, {Bert A.} and Janneke Horn and Majoie, {Charles B.L.M.} and Rinkel, {Gabri{\"e}l J.E.} and Roos, {Yvo B.W.M.} and Vandertop, {W. Peter} and Dagmar Verbaan",

note = "Funding Information: 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, 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. C.J.M. Klijn reports grants from Clinical established investigator grant of the Dutch Heart Foundation (Grant Number 2012T077), grants from ASPASIA, grant from The Netherlands Organization for Health Research and Development, ZonMw (Grant Number 015008048), grants from Support of the Netherlands Cardiovascular Research Initiative, which is supported by the Dutch Heart Foundation, CVON2015–01: CONTRAST, and the support of the Brain Foundation Netherlands (HA2015 01·06), outside the submitted work. 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, 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. The other authors report no relevant disclosures. Go to Neurology.org/N for full disclosures. Publisher Copyright: {\textcopyright} 2022 American Academy of Neurology.",

year = "2022",

month = oct,

day = "20",

doi = "https://doi.org/10.1212/WNL.0000000000201160",

language = "English",

volume = "99",

pages = "E2605--E2614",

journal = "Neurology",

issn = "0028-3878",

publisher = "American Academy of Neurology",

number = "23",

}

Tjerkstra, MA , Post, R, Germans, MR, Vergouwen, MDI, Jellema, K, Koot, RW, Kruyt, ND, Willems, PWA, Wolfs, JFC, De Beer, FC, Kieft, H, Nanda, D, Van Der Pol, B, Roks, G, De Beer, F, Halkes, PHA, Reichman, LJA, Brouwers, PJAM, Van Den Berg-Vos, RM, Kwa, VIH, Van Der Ree, TC, Bronner, I, Bienfait, HP, Boogaarts, H, Klijn, CJM, Van Den Berg, R , Coert, BA , Horn, J , Majoie, CBLM, Rinkel, GJE, Roos, YBWM , Vandertop, WP & Verbaan, D 2022, 'Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post-Hoc Analysis of the ULTRA Trial: Post-Hoc Analysis of the ULTRA Trial', Neurology, vol. 99, no. 23, pp. E2605-E2614. https://doi.org/10.1212/WNL.0000000000201160

TY - JOUR

T1 - Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post-Hoc Analysis of the ULTRA Trial

T2 - Post-Hoc Analysis of the ULTRA Trial

AU - Tjerkstra, Maud A.

AU - Post, René

AU - Germans, Menno R.

AU - Vergouwen, Mervyn D.I.

AU - Jellema, Korné

AU - Koot, Radboud W.

AU - Kruyt, Nyika D.

AU - Willems, Peter W.A.

AU - Wolfs, Jasper F.C.

AU - De Beer, Frits C.

AU - Kieft, Hans

AU - Nanda, Dharmin

AU - Van Der Pol, Bram

AU - Roks, Gerwin

AU - De Beer, Frank

AU - Halkes, Patricia H.A.

AU - Reichman, Loes J.A.

AU - Brouwers, Paul J.A.M.

AU - Van Den Berg-Vos, Renske M.

AU - Kwa, Vincent I.H.

AU - Van Der Ree, Taco C.

AU - Bronner, Irene

AU - Bienfait, Henri P.

AU - Boogaarts, Hieronymus

AU - Klijn, Catharina J.M.

AU - Van Den Berg, René

AU - Coert, Bert A.

AU - Horn, Janneke

AU - Majoie, Charles B.L.M.

AU - Rinkel, Gabriël J.E.

AU - Roos, Yvo B.W.M.

AU - Vandertop, W. Peter

AU - Verbaan, Dagmar

N1 - Funding Information: 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, 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. C.J.M. Klijn reports grants from Clinical established investigator grant of the Dutch Heart Foundation (Grant Number 2012T077), grants from ASPASIA, grant from The Netherlands Organization for Health Research and Development, ZonMw (Grant Number 015008048), grants from Support of the Netherlands Cardiovascular Research Initiative, which is supported by the Dutch Heart Foundation, CVON2015–01: CONTRAST, and the support of the Brain Foundation Netherlands (HA2015 01·06), outside the submitted work. 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, 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. The other authors report no relevant disclosures. Go to Neurology.org/N for full disclosures. Publisher Copyright: © 2022 American Academy of Neurology.

PY - 2022/10/20

Y1 - 2022/10/20

N2 - 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 six months. An expected proportion of the included patients had non-aneurysmal 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 six 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 non-contrast computer tomography, 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 six months, assessed by the modified Rankin Scale, dichotomized into good (0-3) and poor (4-6) outcome.Results: Of the 813 ULTRA-trial patients who had 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% confidence interval (C.I.) 0·69 to 1·24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) aOR 0.76, 95% C.I. 0.57-1.03, all-cause mortality at 30 days aOR 0.91, 95% C.I. 0.65-1.28), all-cause mortality at six months aOR 1.10 (95% C.I. 0.80-1.52).Discussion: Ultra-early and short-term tranexamic acid treatment did not improve clinical outcome at six months in patients with aneurysmal subarachnoid hemorrhage and therefore, cannot be recommended.Trial registration: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24th, 2013).Classification of evidence: This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.

AB - 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 six months. An expected proportion of the included patients had non-aneurysmal 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 six 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 non-contrast computer tomography, 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 six months, assessed by the modified Rankin Scale, dichotomized into good (0-3) and poor (4-6) outcome.Results: Of the 813 ULTRA-trial patients who had 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% confidence interval (C.I.) 0·69 to 1·24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) aOR 0.76, 95% C.I. 0.57-1.03, all-cause mortality at 30 days aOR 0.91, 95% C.I. 0.65-1.28), all-cause mortality at six months aOR 1.10 (95% C.I. 0.80-1.52).Discussion: Ultra-early and short-term tranexamic acid treatment did not improve clinical outcome at six months in patients with aneurysmal subarachnoid hemorrhage and therefore, cannot be recommended.Trial registration: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24th, 2013).Classification of evidence: This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.

UR - http://www.scopus.com/inward/record.url?scp=85141661292&partnerID=8YFLogxK

U2 - https://doi.org/10.1212/WNL.0000000000201160

DO - https://doi.org/10.1212/WNL.0000000000201160

M3 - Article

C2 - 36266046

SN - 0028-3878

VL - 99

SP - E2605-E2614

JO - Neurology

JF - Neurology

IS - 23

ER -

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

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