Prehospital tranexamic acid in trauma and traumatic brain injury: a systematic review with meta-analysis of randomized comparative evidence

 Your competent? doctor put together a protocol on this years ago, right? NO? 

• tranexamic acid (17 posts to March 2013)

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING? Your choice; let them be incompetent or demand action!

Prehospital tranexamic acid in trauma and traumatic brain injury: a systematic review with meta-analysis of randomized comparative evidence

• Khalid Nabeel Almulhim &
• Mohammed Almulhim 

• 12 Accesses

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We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply.

Abstract

Background

Tranexamic acid (TXA) is commonly used in trauma care to decrease bleeding, but its effectiveness and safety in prehospital settings, notably in traumatic brain injury (TBI), remain controversial. This review aimed to systematically evaluate the evidence on prehospital tranexamic acid (TXA) use in trauma and traumatic brain injury (TBI), with quantitative meta-analysis restricted to randomized comparative evidence and non-randomized evidence summarized narratively.

Methods

We conducted a systematic review with quantitative meta-analysis restricted to independent randomized comparative studies evaluating prehospital TXA versus placebo, usual care, or no TXA. Observational studies, secondary analyses, and survey studies were summarized separately and were not pooled with randomized trials in the primary efficacy or safety meta-analysis. outcomes included mortality (28/30-day, in-hospital), thromboembolic events, seizures, and neurological consequences. Risk of bias was evaluated using Cochrane risk of bias tools for randomized controlled trials (RoB2) and non-randomized studies by Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I).

Results

Twenty-one reports met the broad review criteria. The RCT-only analysis of 28- or 30-day mortality included three independent parent randomized trials: PATCH-Trauma/Gruen et al. 2023, STAAMP/Guyette et al. 2021, and ROC-TXA/Rowell et al. 2020. Prehospital TXA was associated with lower 28- or 30-day mortality (RR 0.81, 95% CI 0.68–0.95). The TBI mortality result was derived solely from ROC-TXA/Rowell et al. 2020 and was therefore a single-study estimate rather than a pooled estimate (RR 0.87, 95% CI 0.64–1.20). In-hospital mortality was reported only by STAAMP/Guyette et al. 2021 and was also a single-study estimate (RR 0.87, 95% CI 0.57–1.33). No statistically significant increase in thromboembolic events or seizures was demonstrated. However, the DVT and PE point estimates were above the null, and their wide confidence intervals did not exclude a clinically relevant increase in thromboembolic risk.

Conclusion

Prehospital TXA may reduce 28- or 30-day mortality in selected broader trauma populations, particularly among patients at risk of hemorrhage. No statistically significant increase in thromboembolic events or seizures was demonstrated; however, clinically relevant thromboembolic harm cannot be excluded because the DVT and PE point estimates were above the null, and the confidence intervals were wide.

Tranexamic Acid Cuts Surgical Bleeding in Yet Another Setting

 It was tried on hemorrhages and suggested further research. No clue if that has occurred. Stroke association persons who are paid for keeping track of research should know and since I have a life to live I'm not looking for it.

Effect of Tranexamic Acid Administration on Remote Cerebral Ischemic Lesions in Acute Spontaneous Intracerebral Hemorrhage March 2022

The latest here:

Tranexamic Acid Cuts Surgical Bleeding in Yet Another Setting

But POISE-3 trial leaves open the question of cardiovascular safety

by Crystal Phend, Contributing Editor, MedPage Today April 2, 2022

A dose of tranexamic acid to start and end noncardiac surgery reduced important bleeding events, the POISE-3 trial showed, albeit with a question mark hanging over cardiovascular risk.

The antifibrinolytic drug cut life-threatening, major, or critical organ bleeding by a relative 24% at 30 days compared with placebo (9.1% vs 11.7%, P<0.001), reported P.J. Devereaux, MD, PhD, of the Population Health Research Institute at McMaster University in Hamilton, Ontario, at the American College of Cardiology (ACC) meeting, held virtually and in Washington.

The effect size was similar for fatal bleeds, major bleeds based on International Society on Thrombosis and Haemostasis definition, and transfusion of packed red cells, Devereaux's group reported simultaneously in the New England Journal of Medicine.

However, the primary safety endpoint -- a composite of myocardial injury, nonhemorrhagic stroke, peripheral artery thrombosis, or symptomatic proximal venous thromboembolism at 30 days -- just missed non-inferiority.

The absolute 0.3 percentage point difference between groups (14.2% tranexamic acid vs 13.9% placebo) didn't meet the non-inferiority criterion for the confidence interval upper bound (1.14 vs

"Health care providers and patients will have to weigh a clear beneficial reduction in the incidence of composite bleeding outcome events...against the low probability of a small increase in the incidence of composite cardiovascular outcome events," (absolute difference -2.6 percentage points, 95% CI -3.8 to -1.4), the researchers wrote.

However, the 95.6% probability that the primary safety endpoint was within the needed range for non-inferiority was an "adequate safety signal," said ACC discussant Joseph Cleveland, MD, of the University of Colorado in Aurora, at a press conference.

POISE-3 results carry the potential for "large public health and clinical benefits if tranexamic acid becomes standard practice in noncardiac surgery," given that surgical bleeding accounts for some 40% of all transfusions, Devereaux's group noted.

And it adds to evidence from large trials in cesarean section and in cardiac surgery that also have shown reduced incidence and severity of bleeding, they added. Small trials had also provided supportive data in orthopedic surgery.

Orthopedic surgery is the one noncardiac surgical specialty where there has been some uptake, Devereaux noted.

Results were consistent across patient subgroups, including for orthopedic versus nonorthopedic surgery and for each individual type of surgery considered.

The heterogeneity in types of major operations -- intrathoracic, intraabdominal, retroperitoneal, vascular, and orthopedic -- and inclusion of nonmajor surgeries as some 20% of the procedures -- was surprising, commented ACC discussant Michael Mack, MD, of Baylor Scott & White Health System in Plano, Texas.

I would be a little concerned or hesitant to recommend it in the 20% of nonmajor procedures -- plastic surgery, urology, some of these other procedures that aren't really at risk for major bleeding," he said.

Nevertheless, "This should be more widely used in noncardiac surgery," Mack stated.

Devereaux responded that even among the urology procedures in the trial, bleeding was "reasonably common" and reduced by a similar degree with tranexamic acid as in the overall cohort.

"That does not mean that we're talking about a low-risk, day surgery that this has to happen," he said. "I just want to remind people that in the surgical setting, we often are underestimating the true risk of events."

Also, tranexamic acid is such an inexpensive drug that the economics of it are important in preventing what can be expensive episodes of care for bleeding events, he added.

The Perioperative Ischemic Evaluation-3 (POISE-3) trial randomly assigned 9,535 patients undergoing noncardiac surgery at 114 hospitals across six continents to double-blind treatment with tranexamic acid (1-g IV bolus) or placebo at the start and end of surgery. Patients were ages 45 or older and deemed at risk of bleeding and vascular complications, with those having intracranial neurosurgery or on chronic dialysis excluded. No nonhospital surgical centers or outpatient procedures were included.

Most of the patients had nonorthopedic surgery (77%) and got prophylaxis for venous thromboembolism after surgery (64%). Average age of the participants was 69; 43.9% were women; and 75.9% were white, with 31% enrolled in North America, 40% in Europe, and the rest in the Asia-Pacific region.

The trial had a partial factorial design to randomize patients on long-term antihypertensive medication to compare strategies aimed to avoid hypotension versus hypertension, the results of which are slated for presentation later at the ACC meeting.

One limitation was that the trial was stopped before the last 4% of the planned sample size could be enrolled "owing to a financial deficit resulting from slowed recruitment during the Covid-19 pandemic," the authors stated.

• 

  Crystal Phend is a contributing editor at MedPage Today. Follow

Disclosures

The trial was supported by grants from government agencies in Canada, Australia, and Hong Kong, as well as by the Population Health Research Institute.

Devereaux disclosed relationships with Abbott Canada, Cloud Dx, Roche Diagnostics, and Siemens.

Primary Source

New England Journal of Medicine

Source Reference: Devereaux PJ, et al "Tranexamic Acid in Patients Undergoing Noncardiac Surgery" N Engl J Med 2022; DOI: 10.1056/NEJMoa2201171.

 

Effect of Tranexamic Acid Administration on Remote Cerebral Ischemic Lesions in Acute Spontaneous Intracerebral Hemorrhage

But haven't we already created protocols on this from years of research? No? Then everyone involved is incompetent.

• tranexamic acid (14 posts to March 2013)

 

Effect of Tranexamic Acid Administration on Remote Cerebral Ischemic Lesions in Acute Spontaneous Intracerebral Hemorrhage

A Substudy of a Randomized Clinical Trial

Stefan Pszczolkowski, PhD^1,2,3; Nikola Sprigg, DM^3,4; Lisa J. Woodhouse, MSc³; et al Rebecca Gallagher, MBBChir⁵; David Swienton, MBBChir⁵; Zhe Kang Law, MD, PhD^3,6; Ana M. Casado, MD⁷; Ian Roberts, PhD⁸; David J. Werring, PhD⁹; Rustam Al-Shahi Salman, PhD⁷; Timothy J. England, PhD^3,10; Paul S. Morgan, PhD^1,11,12; Philip M. Bath, DSc^3,4; Robert A. Dineen, PhD^1,2,12

Author Affiliations

JAMA Neurol. Published online March 21, 2022. doi:10.1001/jamaneurol.2022.0217

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Abstract

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Editorial

Comment

• Editorial
  Tranexamic Acid and Diffusion-Weighted Imaging Lesions After Intracerebral Hemorrhage
  Stephanie E. Oh, MD, PhD; Santosh B. Murthy, MD, MPH

Full Text

Key Points

Question  Does intravenous tranexamic acid that is administered after acute spontaneous intracerebral hemorrhage (ICH) increase diffusion-weighted imaging hyperintense lesions?

Findings  In this substudy of a randomized clinical trial involving 219 individuals with acute spontaneous ICH, the prevalence or number of diffusion-weighted imaging hyperintense lesions on brain MRI scans within 2 weeks did not increase in those who received tranexamic acid compared with placebo within 8 hours of acute spontaneous ICH.

Meaning  Findings of this substudy suggest that tranexamic acid is unlikely to increase cerebral ischemic events in acute spontaneous ICH.

Abstract

Importance  Hyperintense foci on diffusion-weighted imaging (DWI) that are spatially remote from the acute hematoma occur in 20% of people with acute spontaneous intracerebral hemorrhage (ICH). Tranexamic acid, a hemostatic agent that is under investigation for treating acute ICH, might increase DWI hyperintense lesions (DWIHLs).

Objective  To establish whether tranexamic acid compared with placebo increased the prevalence or number of remote cerebral DWIHLs within 2 weeks of ICH onset.

Design, Setting, and Participants  This prospective nested magnetic resonance imaging (MRI) substudy of a randomized clinical trial (RCT) recruited participants from the multicenter, double-blind, placebo-controlled, phase 3 RCT (Tranexamic Acid for Hyperacute Primary Intracerebral Hemorrhage [TICH-2]) from July 1, 2015, to September 30, 2017, and conducted follow-up to 90 days after participants were randomized to either the tranexamic acid or placebo group. Participants had acute spontaneous ICH and included TICH-2 participants who provided consent to undergo additional MRI scans for the MRI substudy and those who had clinical MRI data that were compatible with the brain MRI protocol of the substudy. Data analyses were performed on an intention-to-treat basis on January 20, 2020.

Interventions  The tranexamic acid group received 1 g in 100-mL intravenous bolus loading dose, followed by 1 g in 250-mL infusion within 8 hours of ICH onset. The placebo group received 0.9% saline within 8 hours of ICH onset. Brain MRI scans, including DWI, were performed within 2 weeks.

Main Outcomes and Measures  Prevalence and number of remote DWIHLs were compared between the treatment groups using binary logistic regression adjusted for baseline covariates.

Results  A total of 219 participants (mean [SD] age, 65.1 [13.8] years; 126 men [57.5%]) who had brain MRI data were included. Of these participants, 96 (43.8%) were randomized to receive tranexamic acid and 123 (56.2%) were randomized to receive placebo. No baseline differences in demographic characteristics and clinical or imaging features were found between the groups. There was no increase for the tranexamic acid group compared with the placebo group in DWIHL prevalence (20 of 96 [20.8%] vs 28 of 123 [22.8%]; odds ratio [OR], 0.71; 95% CI, 0.33-1.53; P = .39) or mean (SD) number of DWIHLs (1.75 [1.45] vs 1.81 [1.71]; mean difference [MD], −0.08; 95% CI, −0.36 to 0.20; P = .59). In an exploratory analysis, participants who were randomized within 3 hours of ICH onset or those with chronic infarcts appeared less likely to have DWIHLs if they received tranexamic acid. Participants with probable cerebral amyloid angiopathy appeared more likely to have DWIHLs if they received tranexamic acid.

Conclusions and Relevance  This substudy of an RCT found no evidence of increased prevalence or number of remote DWIHLs after tranexamic acid treatment in acute ICH. These findings provide reassurance for ongoing and future trials that tranexamic acid for acute ICH is unlikely to induce cerebral ischemic events.

Trial Registration  isrctn.org Identifier: ISRCTN93732214

• Editorial
  Tranexamic Acid and Diffusion-Weighted Imaging Lesions After Intracerebral Hemorrhage

Comment

 

Safety and Efficacy of Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials

 But we haven't already created protocols on this from years of research? No? Then everyone involved is incompetent.

• tranexamic acid (14 posts to March 2013)

Safety and Efficacy of Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials

Junwei Ren^1†, Dongxi Qian^1†, Jiaming Wu², Lingyan Ni³, Wei Qian¹, Guozheng Zhao¹, Chuanjun Huang¹, Xing Liu¹, Yu Zou¹ and Weikang Xing^1*

• ¹Department of Neurosurgery, Suzhou Ninth People's Hospital, Suzhou, China
• ²Department of Gastroenterology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China
• ³Department of Neurology, The First People's Hospital of Taicang, Suzhou, China

Background: In recent decades, tranexamic acid (TXA) antifibrinolytic therapy before aneurysm clipping or embolization has been widely reported, but its safety and efficacy remain controversial. This meta-analysis evaluated the efficacy and safety of TXA therapy in aneurysmal subarachnoid hemorrhage (aSAH) patients, aiming to improve the evidence-based medical knowledge of treatment options for such patients.

Methods: Pubmed, Web of Science, and Cochrane Library databases were searched up to 1 March 2021 for randomized controlled trials (RCTs). We extracted safety and efficacy outcomes and performed a meta-analysis using the Review Manager software. We performed two group analyses of TXA duration and daily dose.

Results: Ten RCT studies, enrolling a total of 2,810 participants (1,410 with and 1,400 without TXA therapy), matched the selection criteria. In the TXA duration group: TXA did not reduce overall mortality during the follow-up period [RR 1.00 (95% CI 0.81–1.22)]. The overall rebleeding rate in the TXA group was 0.53 times that of the control group, which was statistically significant [RR 0.53 (95% CI 0.39–0.71)]. However, an RR of 0.43 was not statistically significant in the subgroup analysis of short-term therapy [RR 0.43 (95% CI 0.13–1.39)]. The overall incidence of hydrocephalus was significantly higher in the TXA group than in the control group [RR 1.13 (95% CI 1.02–1.24)]. However, the trend was not statistically significant in the subgroup analysis [short-term: RR 1.10 (95% CI 0.99–1.23); long-term: RR 1.22 (95% CI 0.99–1.50)]. Treatment with TXA did not cause significant delayed cerebral ischemia [RR 1.18 (95% CI 0.89–1.56)], and its subgroup analysis showed an opposite and insignificant effect [short-term: RR 0.99 (95% CI 0.79–1.25); long-term: RR 1.38 (95% CI 0.86–2.21)]. Results in the daily dose group were consistent with those in the TXA duration group.

Conclusions: Tranexamic acid does not reduce overall mortality in patients with aSAH, nor does it increase the incidence of delayed cerebral ischemia. Tranexamic acid in treating aSAH can reduce the incidence of rebleeding. However, there is no statisticalsignificance in the ultra-early short-term and low daily dose TXA therapy, which may be due to the lack of relevant studies, and more RCT experiments are needed for further study.

Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.asp? PROSPERO, identifier: 244079.

Introduction

Aneurysm subarachnoid hemorrhage (aSAH) accounts for 5% of all strokes and has an incidence of 7.9 per 100,000 person-years (1). The case fatality rate is ~35% due to initial hemorrhage or subsequent complications. Only 25% of the survivors have a good prognosis (2). In recent decades, tranexamic acid (TXA) antifibrinolytic therapy before aneurysm clipping or embolization has been widely reported, but its safety and efficacy remain controversial (3–6).

Rebleeding from the ruptured aneurysm increases the risk of poor outcomes and all-cause mortality (7). TXA can eliminate fibrinolysis in patients with SAH (8). At the end of the last century, many clinical studies on randomized controlled trials (RCTs) reported that TXA could significantly reduce the incidence of rebleeding in aSAH patients (5, 6, 9–11). Due to the conditions, they could not use TXA in the ultra-early stage for all patients. Moreover, simultaneously, those RCTs were mainly through the long-term (throughout the entire hospitalization) use of TXA. Although long-term antifibrinolytic therapy showed a reduction in rebleeding, the positive clinical outcome was negated by a concomitant rise in delayed cerebral ischemia (DCI) (4). However, most of all rebleeding in aSAH occur within the first 24 h (12). In 2002, Hillman J et al. found it by using TXA ultra-early (within 24 h) and for short-term (up to 72 h), a significant reduction in the rebleeding rate from 10.8 to 2.4% and an 80% reduction in the mortality rate from early rebleeding, without increasing the incidence of delayed ischemic neurological deficits (5). Unfortunately, it did not effectively improve overall mortality or clinical outcomes at 6 months (5).

With the development of diagnostic, therapeutic techniques, and materials, patients with aSAH are identified earlier and treated more successfully. Post et al.'s study, just published in 2021, had the most significant number of participants compared to any other study (13). From onset to first hospital contact for aSAH patients, the time was only 1.5 h, compared with more than 4 h in other trials (5, 6). They used the minimum daily dose of TXA (<4 g/d) for up to 24 h, greatly reducing the effects of delayed cerebral ischemia due to TXA. They noted that TXA might not significantly improve the incidence rate of rebleeding or better patient outcomes. These results were somewhat controversial with previous studies. Thus we produced this meta-analysis to evaluate the efficacy and safety of TXA therapy in aSAH patients.

More at link.

 

Tranexamic Acid for Acute Spontaneous Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials

 But we haven't already created protocols on this from years of research? No? Then everyone involved is incompetent.

• tranexamic acid (13 posts to March 2013)

Tranexamic Acid for Acute Spontaneous Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials

Yu Guo^1†, Xin-Mei Guo^2†, Rui-Li Li^3†, Kai Zhao¹, Qiang-Ji Bao¹, Jin-Cai Yang¹, Qiang Zhang⁴ and Ming-Fei Yang^4*

• ¹Graduate School, Qinghai University, Xining, China
• ²Biomedical Engineering Research Center, Kunming Medical University, Kunming, China
• ³Neurological Intensive Care Department, Shengli Oilfield Central Hospital, Dongying, China
• ⁴Department of Neurosurgery, Qinghai Provincial People's Hospital, Xining, China

Background: The role of tranexamic acid (TXA) in preventing hematoma expansion (HE) in patients with acute spontaneous intracerebral hemorrhage (ICH) remains unclear. We aim to investigate the efficacy and safety of TXA in acute spontaneous ICH with a particular focus on subgroups.

Methods: Randomized controlled trials (RCTs) were retrieved from CENTRAL, Clinicaltrials.gov, EMBASE, PubMed, and WHO ICTRP. The primary outcome measurement was HE. The secondary outcome measurements included 3-month poor functional outcome (PFO), 3-month mortality, and major thromboembolic events (MTE). We conducted subgroup analysis according to the CT markers of HE (standard-risk population and high-risk population) and the time from onset to randomization (>4.5 and ≤4.5 h).

Results: We identified seven studies (representing five RCTs) involving 2,650 participants. Compared with placebo, TXA may reduce HE on subsequent imaging (odd ratio [OR] 0.825; 95% confidence interval [CI] 0.692–0.984; p = 0.033; I² = 0%; GRADE: moderate certainty). TXA and placebo arms did not differ in the rates of 3-month PFO, 3-month mortality, and MTE. Subgroup analysis indicated that TXA reduced the risk of HE in the high-risk population with CT markers of HE (OR 0.646; 95% CI 0.503–0.829; p = 0.001; I² = 0 %) and in patients who were treated within 4.5 h of symptom onset (OR 0.823; 95% CI 0.690–0.980; p = 0.029; I² = 0%), but this protective effect was not observed in the standard-risk population and patients who were treated over 4.5 h of symptom onset.

Conclusions: Tranexamic acid (TXA) may decrease the risk of HE in patients with acute spontaneous ICH. Importantly, the decreased risk was observed in patients who were treatable within 4.5 h and with a high risk of HE, but not in those who were treatable over 4.5 h and in standard-risk population. However, PFO or mortality at 3 months did not significantly differ between patients who received TXA and those who received placebo. TXA is safe for acute spontaneous ICH without increasing MTE.

Introduction

Spontaneous intracerebral hemorrhage (ICH) is one of the leading causes of disability and death worldwide, and is one of the serious global public health and socioeconomic burdens. Globally, up to 3 million people die from ICH each year, accounting for 5% of all human deaths, while an estimated 18 million people suffer from the sequelae of ICH (1, 2). Although an organized in-patient (stroke unit) care has been shown to contribute in reducing disability and mortality, there is no strong evidence-based acute therapy that is specific to acute spontaneous ICH (3, 4).

Age, neurological deficit, hemorrhage cause, location, and hematoma volume are the main determinants of clinical outcomes in patients with ICH (5, 6). Among them, hematoma volume is the most important factor. Roughly one-third of acute spontaneous ICH are complicated by hematoma expansion (HE), which most often occurs within the first few hours, but could also occur at up to 24 h, presenting a target window for intervention (7, 8). Emergency medical services are traditionally established to bring in patients with acute stroke with haste for diagnosis and treatment within 4.5 h of symptom onset. In addition, tranexamic acid (TXA) therapy is theoretically more suitable for patients with high-risk for ICH growth, such as patients with early computed tomography (CT) markers of HE. CT markers, including black hole sign, blend sign, island sign, and spot sign, have been used as reliable predictors for early HE in patients with acute spontaneous ICH (9–14). Therefore, it seems feasible to identify patients at high risk for HE early, and then for early therapeutic intervention to improve the clinical outcomes of patients with acute spontaneous ICH.

The researchers are looking for a safe acute therapy to reduce the risk of HE and improve the outcome for acute spontaneous ICH patients. TXA is an antifibrinolytic agent that reduces bleeding by inhibiting plasminogen activation and fibrinolysis. It has been shown that it can reduce perioperative blood loss and risk of blood transfusion (15, 16). In addition, trauma guidelines have recommended the early use of TXA in patients with traumatic ICH, as TXA can provide a survival benefit without increasing its adverse events (17, 18). However, the role of TXA in preventing HE and in improving outcome in patients with acute spontaneous ICH remains unclear.

Several randomized controlled trials (RCTs) evaluating the efficacy and safety of TXA in patients with acute spontaneous ICH have been performed in recent years. However, the existing RCTs and previously published systematic reviews have reported fragmentary and conflicting results. Some studies have shown a protective association between TXA use and ICH growth. Other studies have found no such relationship. These studies differed in their study populations. Herein, we performed meta-analysis on the available RCTs to determine the following: (1) the effectiveness and safety of TXA administration, compared against placebo or open control, in adults with acute spontaneous ICH; (2) how this differs between the standard-risk population and the high-risk population (those with ICH with CT markers of HE); and (3) how this differs between the range within 4.5 h and over 4.5 h of the time from onset to randomization.

More at link.

 

Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial

WHOM is going to look into this as a possible intervention for certain types of hemorrhages? Specific names only.

But what about this research?

Tranexamic Acid Shows No Symptom Benefit for Traumatic Brain Injuries

September 2020

And earlier research for hemorrhages:

Predictors and Outcomes of Neurological Deterioration in Intracerebral Hemorrhage: Results from the TICH-2 Randomized Controlled Trial

September 2020

A paragraph from there:

Tranexamic acid reduced the risk of early (aOR 0.79, 0.63–0.99; p = 0.041) but not late neurological deterioration (aOR 0.76, 0.52–1.11; p = 0.15). Larger hematoma size, intraventricular and subarachnoid extension increased the risk of neurological deterioration. Neurological deterioration increased the risk of death and dependency at day 90. Tranexamic acid reduced the risk of early neurological deterioration and warrants further investigation in ICH. URL:https://www.isrctn.com Unique identifier: ISRCTN93732214

I expect your doctor to know everything about this.

The latest here:

Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial

• The CRASH-3 trial collaborators
  ^†
• Show footnotes

Open AccessPublished:October 14, 2019DOI:https://doi.org/10.1016/S0140-6736(19)32233-0

PlumX Metrics

Summary

Background

Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury (TBI) and can cause brain herniation and death. We aimed to assess the effects of tranexamic acid in patients with TBI.

Methods

This randomised, placebo-controlled trial was done in 175 hospitals in 29 countries. Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible. The time window for eligibility was originally 8 h but in 2016 the protocol was changed to limit recruitment to patients within 3 h of injury. This change was made blind to the trial data, in response to external evidence suggesting that delayed treatment is unlikely to be effective. We randomly assigned (1:1) patients to receive tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury. We prespecified a sensitivity analysis that excluded patients with a GCS score of 3 and those with bilateral unreactive pupils at baseline. All analyses were done by intention to treat. This trial was registered with ISRCTN (ISRCTN15088122), ClinicalTrials.gov (NCT01402882), EudraCT (2011-003669-14), and the Pan African Clinical Trial Registry (PACTR20121000441277).

Results

Between July 20, 2012, and Jan 31, 2019, we randomly allocated 12 737 patients with TBI to receive tranexamic acid (6406 [50·3%] or placebo [6331 [49·7%], of whom 9202 (72·2%) patients were treated within 3 h of injury. Among patients treated within 3 h of injury, the risk of head injury-related death was 18·5% in the tranexamic acid group versus 19·8% in the placebo group (855 vs 892 events; risk ratio [RR] 0·94 [95% CI 0·86–1·02]). In the prespecified sensitivity analysis that excluded patients with a GCS score of 3 or bilateral unreactive pupils at baseline, the risk of head injury-related death was 12·5% in the tranexamic acid group versus 14·0% in the placebo group (485 vs 525 events; RR 0·89 [95% CI 0·80–1·00]). The risk of head injury-related death reduced with tranexamic acid in patients with mild-to-moderate head injury (RR 0·78 [95% CI 0·64–0·95]) but not in patients with severe head injury (0·99 [95% CI 0·91–1·07]; p value for heterogeneity 0·030). Early treatment was more effective than was later treatment in patients with mild and moderate head injury (p=0·005) but time to treatment had no obvious effect in patients with severe head injury (p=0·73). The risk of vascular occlusive events was similar in the tranexamic acid and placebo groups (RR 0·98 (0·74–1·28). The risk of seizures was also similar between groups (1·09 [95% CI 0·90–1·33]).

Interpretation

Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury.

Funding

National Institute for Health Research Health Technology Assessment, JP Moulton Charitable Trust, Department of Health and Social Care, Department for International Development, Global Challenges Research Fund, Medical Research Council, and Wellcome Trust (Joint Global Health Trials scheme).

Translations

For the Arabic, Chinese, French, Hindi, Japanese, Spanish and Urdu translations of the abstract see Supplementary Material section.

Introduction

Each year, worldwide, there are more than 60 million new cases of traumatic brain injury (TBI).

¹

Road traffic crashes and falls are the main causes and the incidence is increasing.

¹

Intracranial bleeding is a common complication of TBI and increases the risk of death and disability.

²

Although bleeding can start from the moment of impact, it often continues for several hours after injury.

³

^, 

⁴

Ongoing intracranial bleeding can lead to raised intracranial pressure, brain herniation, and death. Tranexamic acid reduces bleeding by inhibiting the enzymatic breakdown of fibrin blood clots (fibrinolysis). The CRASH-2 trial

⁵

^, 

⁶

showed that in patients with trauma with major extracranial bleeding, early administration (within 3 h of injury) of tranexamic acid reduces bleeding deaths by a third. Subsequent analyses showed that even a short delay in treatment reduces the benefit of tranexamic acid administration.

⁷

On the basis of these results, tranexamic acid was included in guidelines for the pre-hospital care of patients with trauma, although patients with isolated TBI were specifically excluded. However, increased fibrinolysis, as indicated by increased concentrations of fibrinogen degradation products, is often seen in patients with TBI and predicts intracranial haemorrhage expansion.

⁸

Therefore, early administration of tranexamic acid in patients with TBI might prevent or reduce intracranial haemorrhage expansion and thus avert brain herniation and death.

 

Tranexamic Acid Shows No Symptom Benefit for Traumatic Brain Injuries

 Well have your doctor analyze this previous research which showed benefits.

Did your incompetent stroke hospital DO ANYTHING with ANY of this earlier research? 

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): An international randomised, placebo-controlled, phase 3 superiority trial

May 2018, this one actually supposedly was negative.

 

Drug to treat bleeding may benefit some stroke patients, study finds May 2018

 

The Lancet: Immediate treatment with clot-stabilising drug could save thousands of additional lives every year November 2017

 

Treatment of intracerebral haemorrhage with tranexamic acid – A review of current evidence and ongoing trials October 2016

 

New guidance for administering hemorrhage prevention treatment August 2016

 

UBC researchers create self-propelled powder to stop bleeding October 2015

 

UC to Study New Drug in Patients with Traumatic Brain Injury June 2014

 

University of Nottingham to study use of tranexamic acid in people with intracerebral haemorrhage March 2013

I bet they will incompetently DO NOTHING because it is easier to wait for SOMEONE ELSE TO SOLVE THE PROBLEM?   

The latest here for your stroke hospital and doctors to ignore. 

Tranexamic Acid Shows No Symptom Benefit for Traumatic Brain Injuries

Favorable neurologic function was slightly higher in a tranexamic acid group than patients taking a placebo.

Susan E. Rowell, MD

The early administration of tranexamic acid is not beneficial for patients suffering from traumatic brain injuries (TBI), according to new data.

A team, led by Susan E. Rowell, MD, Department of Surgery, Oregon Health & Science University, determined whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of an injury could improve neurologic outcomes of patients with moderate-to-severe traumatic brain injuries.

In the randomized, multicenter double-blind clinical trial, the investigators examined 966 patients at 20 trauma centers and 39 emergency medical service agencies in the US and Canada between May 2015 and November 2017. The mean age of the patient population was 42 years old and 74% of the participants were male. The mean Glasgow Coma Scale score was 8 and 819 patients ended up in the primary outcome analysis at the six-month follow-up.

Eligible patients included out-of-hospital patients with TBI at least 15 years old with a Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher.

The investigators evaluated 3 different interventions, with treatment initiated within 2 hours of an injury—out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309).

The research team sought primary outcomes of favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. They set the asymmetric significance thresholds at 0.1 for benefit and 0.025 for harm.

There were also 18 secondary endpoints in the study, including 28-day mortality, six-month Disability Rating Scale score range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events.

Favorable neurologic function was found in 65% of patients in the tranexamic acid group, compared to 62% of the placebo group (difference, 3.5%; 90% 1-sided confidence limit for benefit, −0.9%; P = 0.16; 97.5% 1-sided confidence limit for harm, 10.2%; P = 0 .84).

The researchers did not find a statistically significant difference in the 28-day mortality between the 2 groups (14% vs 17%; difference, −2.9%; 95% CI, −7.9% to 2.1%; P = 0.26).

This was also found in the 6-month Disability Rating Scale score (6.8 vs 7.6; difference, −0.9; 95% CI, −2.5 to 0.7; P = 0.29) and the progression of intracranial hemorrhage (16% vs 20%; difference, −5.4%; 95% CI, −12.8% to 2.1%; P = 0 .16).

“Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended,” the authors wrote.

Currently, TBI is the leading cause of death and disability caused by trauma.

The study, “Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury,” was published online by JAMA.

 

Predictors and Outcomes of Neurological Deterioration in Intracerebral Hemorrhage: Results from the TICH-2 Randomized Controlled Trial

Survivors don't need more predictions of failure to recover. THEY NEED 100% RECOVERY PROTOCOLS. GET THERE! Useless crapola.

Predictors and Outcomes of Neurological Deterioration in Intracerebral Hemorrhage: Results from the TICH-2 Randomized Controlled Trial

 

• Zhe Kang Law,
• Rob Dineen,
• Timothy J England,
• Lesley Cala,
• Amit K Mistri,
• Jason P Appleton,
• Serefnur Ozturk,
• Daniel Bereczki,
• Alfonso Ciccone,
• Philip M Bath,
• Nikola Sprigg &
• on behalf of TICH-2 investigators

Translational Stroke Research (2020)Cite this article

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Abstract

Neurological deterioration is common after intracerebral hemorrhage (ICH). We aimed to identify the predictors and effects of neurological deterioration and whether tranexamic acid reduced the risk of neurological deterioration. Data from the Tranexamic acid in IntraCerebral Hemorrhage-2 (TICH-2) randomized controlled trial were analyzed. Neurological deterioration was defined as an increase in National Institutes of Health Stroke Scale (NIHSS) of ≥ 4 or a decline in Glasgow Coma Scale of ≥ 2. Neurological deterioration was considered to be early if it started ≤ 48 h and late if commenced between 48 h and 7 days after onset. Logistic regression was used to identify predictors and effects of neurological deterioration and the effect of tranexamic acid on neurological deterioration. Of 2325 patients, 735 (31.7%) had neurological deterioration: 590 (80.3%) occurred early and 145 (19.7%) late. Predictors of early neurological deterioration included recruitment from the UK, previous ICH, higher admission systolic blood pressure, higher NIHSS, shorter onset-to-CT time, larger baseline hematoma, intraventricular hemorrhage, subarachnoid extension and antiplatelet therapy. Older age, male sex, higher NIHSS, previous ICH and larger baseline hematoma predicted late neurological deterioration. Neurological deterioration was independently associated with a modified Rankin Scale of > 3 (aOR 4.98, 3.70–6.70; p < 0.001). Tranexamic acid reduced the risk of early (aOR 0.79, 0.63–0.99; p = 0.041) but not late neurological deterioration (aOR 0.76, 0.52–1.11; p = 0.15). Larger hematoma size, intraventricular and subarachnoid extension increased the risk of neurological deterioration. Neurological deterioration increased the risk of death and dependency at day 90. Tranexamic acid reduced the risk of early neurological deterioration and warrants further investigation in ICH. URL:https://www.isrctn.com Unique identifier: ISRCTN93732214

Introduction

Neurological deterioration affects approximately one-third of patients with spontaneous intracerebral hemorrhage (ICH) and increases the risk of death and dependency [1,2,3]. Older age, prior use of anticoagulant, larger baseline hematoma, CT angiography spot sign, hematoma expansion, perihematomal edema, intraventricular hemorrhage, subarachnoid extension, hydrocephalus and leukoaraiosis were reported to increase the risk of neurological deterioration after ICH in previous studies [2,3,4,5,6]. Nevertheless, apart from hematoma expansion, reports of other neurological and systemic complications associated with neurological deterioration were not well documented [2,3,4,5,6].

Tranexamic acid is an antifibrinolytic agent that was effective in preventing death due to bleeding in major trauma and traumatic brain injury [7, 8]. In the Tranexamic acid in Intracerebral Hemorrhage-2 (TICH-2) trial, there was no significant difference in death and dependency at day 90 between ICH patients treated with tranexamic acid and placebo [9]. However, there was a significant reduction in the rates of hematoma expansion, early death and serious adverse events with tranexamic acid [9].