Rationale and Design of a Randomized, Double-Blind Trial Evaluating the Efficacy of Tranexamic Acid on Hematoma Expansion and Peri-hematomal Edema in Patients with Spontaneous Intracerebral Hemorrhage within 4.5 h after Symptom Onset: The THE-ICH Trial Protocol

Background and Purpose: The computed tomography angiography or contrast-enhanced computed tomography based spot sign has been proposed as a biomarker for identifying on-going hematoma expansion in patients with acute intracerebral hemorrhage. We investigated, if spot-sign positive participants benefit more from tranexamic acid versus placebo as compared to spot-sign negative participants. Methods: TICH-2 trial (Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage) was a randomized, placebo-controlled clinical trial recruiting acutely hospitalized participants with intracerebral hemorrhage within 8 hours after symptom onset. Local investigators randomized participants to 2 grams of intravenous tranexamic acid or matching placebo (1:1). All participants underwent computed tomography scan on admission and on day 2 (24±12 hours) after randomization. In this sub group analysis, we included all participants from the main trial population with imaging allowing adjudication of spot sign status. Results: Of the 2325 TICH-2 participants, 254 (10.9%) had imaging allowing for spot-sign adjudication. Of these participants, 64 (25.2%) were spot-sign positive. Median (interquartile range) time from symptom onset to administration of the intervention was 225.0 (169.0 to 310.0) minutes. The adjusted percent difference in absolute day-2 hematoma volume between participants allocated to tranexamic versus placebo was 3.7% (95% CI, −12.8% to 23.4%) for spot-sign positive and 1.7% (95% CI, −8.4% to 12.8%) for spot-sign negative participants ( P heterogenity =0.85). No difference was observed in significant hematoma progression (dichotomous composite outcome) between participants allocated to tranexamic versus placebo among spot-sign positive (odds ratio, 0.85 [95% CI, 0.29 to 2.46]) and negative (odds ratio, 0.77 [95% CI, 0.41 to 1.45]) participants ( P heterogenity =0.88). Conclusions: Data from the TICH-2 trial do not support that admission spot sign status modifies the treatment effect of tranexamic acid versus placebo in patients with acute intracerebral hemorrhage. The results might have been affected by low statistical power as well as treatment delay. REGISTRATION: URL: http://www.controlled-trials.com ; Unique identifier: ISRCTN93732214.

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Tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign trial: Rationale and design

International Journal of Stroke ◽

10.1177/1747493017694394 ◽

2017 ◽

Vol 12 (3) ◽

pp. 326-331 ◽

Cited By ~ 10

Author(s):

Liping Liu ◽

Yilong Wang ◽

Xia Meng ◽

Na Li ◽

Ying Tan ◽

...

Keyword(s):

High Risk ◽

Intracerebral Hemorrhage ◽

Tranexamic Acid ◽

Primary Outcome Measure ◽

Hematoma Expansion ◽

Spot Sign ◽

Double Blind ◽

Risk Patients ◽

Acute Intracerebral Hemorrhage ◽

Hemorrhage Volume

Rationale Acute intracerebral hemorrhage inflicts a high-economic and -health burden. Computed tomography angiography spot sign is a predictor of hematoma expansion, is associated with poor clinical outcome and is an important stratifying variable for patients treated with haemostatic therapy. Aims We aim to compare the effect of treatment with tranexamic acid to placebo for the prevention of hemorrhage growth in patients with high-risk acute intracerebral hemorrhage with a positive spot sign. Design The tranexamic acid for acute intracerebral hemorrhage growth predicted by spot sign (TRAIGE) is a prospective, multicenter, placebo-controlled, double-blind, investigator-led, randomized clinical trial that will include an estimated 240 participants. Patients with intracerebral hemorrhage demonstrating symptom onset within 8 h and with the spot sign as a biomarker for ongoing hemorrhage, and no contraindications for antifibrinolytic therapy, will be enrolled to receive either tranexamic acid or placebo. The primary outcome measure is the presence of hemorrhage growth defined as an increase in intracerebral hemorrhage volume >33% or >6 ml from baseline to 24 ± 2 h. The secondary outcomes include safety and clinical outcomes. Conclusion The TRAIGE trial evaluates the efficacy of haemostatic therapy with tranexamic acid in the prevention of hemorrhage growth among high-risk patients with acute intracerebral hemorrhage.

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Treatment of Menorrhagia with Tranexamic Acid. A Double-blind Trial

BMJ ◽

10.1136/bmj.4.5729.214 ◽

1970 ◽

Vol 4 (5729) ◽

pp. 214-216 ◽

Cited By ~ 76

Author(s):

S. L. T. Callender ◽

G. T. Warner ◽

E. Cope

Keyword(s):

Tranexamic Acid ◽

Double Blind Trial ◽

Double Blind ◽

Blind Trial

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

Frontiers in Neurology ◽

10.3389/fneur.2021.761185 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yu Guo ◽

Xin-Mei Guo ◽

Rui-Li Li ◽

Kai Zhao ◽

Qiang-Ji Bao ◽

...

Keyword(s):

High Risk ◽

Intracerebral Hemorrhage ◽

Tranexamic Acid ◽

Symptom Onset ◽

High Risk Population ◽

Controlled Trials ◽

Spontaneous Intracerebral Hemorrhage ◽

Risk Population ◽

Randomized Controlled ◽

Standard Risk

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.

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Intravenous vs Intra-Articular Tranexamic Acid in Total Knee Arthroplasty: A Randomized, Double-Blind Trial

The Journal of Arthroplasty ◽

10.1016/j.arth.2016.07.004 ◽

2017 ◽

Vol 32 (1) ◽

pp. 28-32 ◽

Cited By ~ 24

Author(s):

Navendu Goyal ◽

Darren B. Chen ◽

Ian A. Harris ◽

Neville J. Rowden ◽

George Kirsh ◽

...

Keyword(s):

Total Knee Arthroplasty ◽

Tranexamic Acid ◽

Knee Arthroplasty ◽

Double Blind Trial ◽

Double Blind ◽

Blind Trial ◽

Total Knee

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Outcomes in Antiplatelet‐Associated Intracerebral Hemorrhage in the TICH‐2 Randomized Controlled Trial

Journal of the American Heart Association ◽

10.1161/jaha.120.019130 ◽

2021 ◽

Author(s):

Zhe Kang Law ◽

Michael Desborough ◽

Ian Roberts ◽

Rustam Al‐Shahi Salman ◽

Timothy J. England ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Tranexamic Acid ◽

Functional Outcome ◽

Antiplatelet Therapy ◽

Controlled Trial ◽

Hematoma Expansion ◽

Modified Rankin Scale ◽

Double Blind ◽

Risk Of Death ◽

Increased Risk

Background Antiplatelet therapy increases the risk of hematoma expansion in intracerebral hemorrhage (ICH) while the effect on functional outcome is uncertain. Methods and Results This is an exploratory analysis of the TICH‐2 (Tranexamic Acid in Intracerebral Hemorrhage‐2) double‐blind, randomized, placebo‐controlled trial, which studied the efficacy of tranexamic acid in patients with spontaneous ICH within 8 hours of onset. Multivariable logistic regression and ordinal regression were performed to explore the relationship between pre‐ICH antiplatelet therapy, and 24‐hour hematoma expansion and day 90 modified Rankin Scale score, as well as the effect of tranexamic acid. Of 2325 patients, 611 (26.3%) had pre‐ICH antiplatelet therapy. They were older (mean age, 75.7 versus 66.5 years), more likely to have ischemic heart disease (25.4% versus 2.7%), ischemic stroke (36.2% versus 6.3%), intraventricular hemorrhage (40.2% versus 27.5%), and larger baseline hematoma volume (mean, 28.1 versus 22.6 mL) than the no‐antiplatelet group. Pre‐ICH antiplatelet therapy was associated with a significantly increased risk of hematoma expansion (adjusted odds ratio [OR], 1.28; 95% CI, 1.01–1.63), a shift toward unfavorable outcome in modified Rankin Scale (adjusted common OR, 1.58; 95% CI, 1.32–1.91) and a higher risk of death at day 90 (adjusted OR, 1.63; 95% CI, 1.25–2.11). Tranexamic acid reduced the risk of hematoma expansion in the overall patients with ICH (adjusted OR, 0.76; 95% CI, 0.62–0.93) and antiplatelet subgroup (adjusted OR, 0.61; 95% CI, 0.41–0.91) with no significant interaction between pre‐ICH antiplatelet therapy and tranexamic acid (P interaction=0.248). Conclusions Antiplatelet therapy is independently associated with hematoma expansion and unfavorable functional outcome. Tranexamic acid reduced hematoma expansion regardless of prior antiplatelet therapy use. Registration URL: https://www.isrctn.com ; Unique identifier: ISRCTN93732214.

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