Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial

Post, René; Germans, Menno R.; Tjerkstra, Maud A.; Vergouwen, Mervyn D.I.; Jellema, Korné; Koot, Radboud W.; Kruyt, Nyika D.; Willems, Peter W. A.; Wolfs, Jasper F. C.; Beer, F; Kieft, Hans; Nanda, Dharmin; Pol, B. van der; Roks, Gerwin; Beer, Frank de; Halkes, Patricia H.A.; Reichman, Loes J A; Brouwers, P. J. A. M.; Berg-Vos, Renske M. Van den; Kwa, Vincent I H; Ree, Taco C van der; Bronner, I. M.; Vlekkert, J. van de; Bienfait, Henri Paul; Boogaarts, Hieronymus D.; Klijn, Catharina J.M.; Berg, René van den; Coert, Bert A.; Horn, Janneke; Majoie, Charles B. L. M.; Rinkel, Gabriël J.E.; Roos, Yvo B.W.E.M.; Vandertop, W. Peter; Verbaan, Dagmar; Bilzen, Martine van; Dieks, H.J.G.; Gans, Koen de; Holter, J.B.M. ten; Kruijk, Jelle R. de; Leijzer, Charlie T.J.M.; Molenaar, D.S.M.; Oostenbrugge, Robbert J. van; Pamelen, Jeske van; Spaander, Fianne; Vermeer, Sarah E.; Voorend, J. Manuela

doi:10.1016/s0140-6736(20)32518-6

Cited by 132 publications

(132 citation statements)

References 21 publications

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“…Roos et al concluded that the use of TXA with standard treatment did not improve patient outcomes [ 38 ]. In 2021, the ULTRA trial also concluded that the use of tranexamic acid did not show improved clinical outcomes defined by the modified Rankin score (mRS) at 6 months [ 39 ]. The Neurocritical Care Society does endorse that TXA and aminocaproic acid can reduce aneurysmal re-rupture; however, they have also been shown to increase risk of deep venous thrombosis, pulmonary embolus, and ischemic stroke if used for prolonged periods of time [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Subarachnoid hemorrhage in the emergency department

2021

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Background Subarachnoid hemorrhage accounts for more than 30,000 cases of stroke annually in North America and encompasses a 4.4% mortality rate. Since a vast number of subarachnoid hemorrhage cases present in a younger population and can range from benign to severe, an accurate diagnosis is imperative to avoid premature morbidity and mortality. Here, we present a straightforward approach to evaluating, risk stratifying, and managing subarachnoid hemorrhages in the emergency department for the emergency medicine physician. Discussion The diversities of symptom presentation should be considered before proceeding with diagnostic modalities for subarachnoid hemorrhage. Once a subarachnoid hemorrhage is suspected, a computed tomography of the head with the assistance of the Ottawa subarachnoid hemorrhage rule should be utilized as an initial diagnostic measure. If further investigation is needed, a CT angiography of the head or a lumbar puncture can be considered keeping risks and limitations in mind. Initiating timely treatment is essential following diagnosis to help mitigate future complications. Risk tools can be used to assess the complications for which the patient is at greatest. Conclusion Subarachnoid hemorrhages are frequently misdiagnosed; therefore, we believe it is imperative to address the diagnosis and initiation of early management in the emergency medicine department to minimize poor outcomes in the future.

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Section: Discussionmentioning

confidence: 99%

Subarachnoid hemorrhage in the emergency department

2021

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“…After assessing 22 full-text for eligibility, we excluded 15 because 1)no control group(n=7), 2)case report, 3)non-RCT studies (n=7). Therefore, seven articles were included in the qualitative synthesis [7,[11][12][13][14][15][16]. A total of 2917 patients from 7 RCTs were randomly assigned to TXA treatment (n = 1403) or placebo (n = 1514) for meta-analysis.…”

Section: Description Of Included Studiesmentioning

confidence: 99%

“…Each group included 29 to 480 patients. The largest RCT population was a multicenter study published in 2021 [7]. Three studies were open-label RCTs [7,11,16], while the remaining four were double-blind RCTs [12][13][14][15].…”

Section: Description Of Included Studiesmentioning

confidence: 99%

“…In 2003, a Cochrane Review demonstrated that TXA showed a bene cial effect on reducing rebleeding but failed to show good clinical outcomes, possibly because the bene t was offset by an increase in adverse events due to cerebral ischemia [5].TXA with concomitant treatment strategies to prevent cerebral ischemia also showed a bene cial effect on reducing rebleeding; nonetheless, the effect of tranexamic acid on good clinical outcomes remained unclear [6]. Recently, the ULTRA, a multicenter prospective, randomized, controlled, open-label trial with 955 participants from 8 treatment centers and 16 referring hospitals, assessed the effects of ultra-early tranexamic acid for aneurysmal SAH and showed a slight reduction in mortality but not in rebleeding after randomization and before aneurysm treatment as well as in the improvement of clinical outcome at 6 months [7]. Some comments suggest that it might be associated with increased incidence of hydrocephalus and epilepsy [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Meta-analysis of Randomized Controlled Trials

Liu

Ding

Xue

2021

Preprint

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BackgroundTranexamic acid, as a hemostatic drug, is widely used to treat or prevent excessive blood loss. The efficacy of tranexamic acid in promoting good clinical outcomes, reducing mortality, and the occurrence of adverse events during treatment of aneurysmal subarachnoid hemorrhage remains unclear.MethodsPubMed, Web of Science, Embase, and The Cochrane Library were searched for randomized-controlled trials (from1980 to 2021) following strict inclusion and exclusion criteria. We performed STATA 16.0 and RevMan 5.3 for statistical analysis. Fixed-effect model (M-H method) and effect size RR (95% CI) were used as a pooled measure to combine the heterogeneous data. We also performed post hoc sensitivity analyses and conducted subgroup analyses to evaluate each outcome with low heterogeneity results.ResultsMeta-analysis showed that tranexamic acid was associated with reduced rebleeding(RR 0.72 [0.59, 0.87], p= 0.0008; I2:0%, p = 0.51). Tranexamic acid probably has no effect on good clinical outcome or mortality (RR 0.98 [0.92,1.04], p = 0.51; I2: 0%, p = 0.60; RR 1.01 [0.88,1.15], p=0.91; I2:0%, p = 0.51).TXA was associated with increased hydrocephalus (RR 1.13 [1.02, 1.24], p = 0.02; I2:0%, p = 0.61), DCI (RR 1.70 [1.34, 2.16], p < 0.0001; I2: 0%, p= 0.84) and seizure (RR 1.46 [1.00, 2.14], p= 0.05),The rate for thromboembolic complications were similar in both groups(RR 0.91 [0.63, 1.31], p = 0.62;I2: 0%, p = 0.73). There was significant drug related overall adverse events (RR 1.21 [1.11, 1.32], p < 0.0001; I2: 29%, p = 0.14).ConclusionsIn patients with aneurysmal subarachnoid hemorrhage, these findings indicate that it does not support the routine use of TXA.

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“…For example, the CRASH‐2 4 and WOMAN 5 trials on the use of tranexamic acid (TXA) in massive bleeding in trauma or post‐partum hemorrhage may have led to the assumption that TXA should be part of (massive) bleeding protocols in general. However, TXA was ineffective and caused harm in the HALT‐IT trial on gastrointestinal (GI) bleeding 6 and was ineffective in the ULTRA trial on patients with subarachnoid hemorrhage 7 . Also, although blood components such as fresh frozen plasma (FFP), platelet concentrates, and coagulation factor concentrates are frequently used in prevention and treatment of bleeding, there is very little evidence these treatments are effective 8‐10 .…”

Section: Introductionmentioning

confidence: 99%

Treatment of bleeding in patients with liver disease

Lisman

Roberts

2021

Journal of Thrombosis and Haemostasis

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Patients with cirrhosis frequently have complex alterations in their hemostatic system. Although routine diagnostic tests of hemostasis in cirrhosis (platelet count, prothrombin time, fibrinogen level) are suggestive of a bleeding tendency, it is now widely accepted that these tests do not reflect hemostatic competence in this population. Rather, patients with cirrhosis appear to have a rebalanced hemostatic system with hypercoagulable elements. Therefore, routine correction of hemostasis laboratory values, for example by fresh frozen plasma or platelet concentrates, with the aim to avoid spontaneous or procedure‐related bleeding is not indicated as is outlined in recent clinical guidance documents. However, little guidance on how to manage patients with cirrhosis that are actively bleeding is available. Here we present three common bleeding scenarios, variceal bleeding, post‐procedural bleeding and bleeding in a critically ill cirrhosis patient, with specific management suggestions. As patients with cirrhosis generally have adequate hemostatic competence and as bleeding complications may be unrelated to hemostatic failure, prohemostatic therapy is not the first line of management in bleeding patients with cirrhosis, even in the presence of markedly abnormal platelet counts and/or prothrombin times. We provide a rationale for the restrictive approach to prohemostatic therapy in bleeding patients with cirrhosis.

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Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial

Cited by 132 publications

References 21 publications

Subarachnoid hemorrhage in the emergency department

Subarachnoid hemorrhage in the emergency department

Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Meta-analysis of Randomized Controlled Trials

Treatment of bleeding in patients with liver disease

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