Tranexamic acid for hyperacute spontaneous IntraCerebral Haemorrhage (TICH-3)

The primary objective of the study titled "Tranexamic acid for hyperacute spontaneous IntraCerebral Haemorrhage (TICH-3)" is to evaluate the clinical effectiveness of **tranexamic acid (TXA)** in patients with hyperacute spontaneous intracerebral hemorrhage (ICH). Specifically, the study aims to determine the impact of TXA on early mortality, defined as death occurring within 7 days post-ICH. This objective is clinically significant as it addresses the potential of TXA to reduce early mortality in a condition where rapid intervention is critical.

The secondary objective is to assess the effect of TXA on patient dependency 6 months following ICH. This evaluation is important for understanding the long-term benefits of TXA in improving patient outcomes and quality of life post-ICH.

The clinical trial involves a total of **3984 participants** diagnosed with **stroke**, specifically focusing on the assessment of tranexamic acid (TXA) after intracerebral hemorrhage (ICH). The study population includes both male and female adults aged 18 years and older. Participants were selected based on their presentation within 4.5 hours of the onset of acute spontaneous ICH, confirmed through brain imaging. The trial includes individuals who are taking direct oral anticoagulants. The population is characterized by a vulnerable group, as indicated by the inclusion of individuals with acute medical conditions. Lifestyle factors such as diet and physical activity are not specified in the available data. The selection criteria ensure that participants have no other exclusion criteria and have provided informed consent in accordance with regulatory requirements.

The clinical trial is designed to evaluate the **clinical effectiveness** of **tranexamic acid** (TXA) in patients with hyperacute spontaneous intracerebral hemorrhage (ICH). This study is a randomized, double-blind, controlled trial, with participants receiving either TXA or a placebo, specifically **sodium chloride** injection. The trial aims to assess the impact of TXA on early mortality, defined as death within seven days post-ICH onset, and on dependency six months after the event. The trial is expected to run from March 2023 to June 2028, with participant involvement lasting up to seven days for the primary outcome assessment and six months for secondary outcomes.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), presentation within 4.5 hours of ICH onset, and confirmation of ICH via brain imaging. Follow-up visits will occur to monitor the primary endpoint of early death and secondary endpoints related to dependency. The end-of-study visit will evaluate the long-term effects of TXA on patient outcomes. The expected length of participant involvement is up to six months, with the primary focus on the initial seven days post-treatment. Conditions that may lead to early termination from the study include the occurrence of serious adverse events such as seizures or thromboembolic events within the first seven days.

The clinical trial involves the administration of **Cyklokapron**, a **tranexamic acid** solution for injection/infusion, manufactured by Pfizer Limited. This pharmaceutical form is a solution for injection/infusion, with a concentration of 100 mg/mL. The active substance, tranexamic acid, is of chemical origin. The maximum daily dose and total dose amount are both set at 2 grams. The administration route is via infusion, and the maximum treatment period is one day. The product is authorized under the marketing authorization number PL 00057/0952 and is classified under the ATC code B02AA02, which pertains to tranexamic acid. The product is not a pediatric formulation and is used as the test treatment in the trial.

The comparator treatment in the trial is **Sodium Chloride Injection BP 0.9% w/v**, provided by Hameln Pharma Ltd. This solution for injection serves as a placebo in the study. The active substance, **sodium chloride**, is also of chemical origin. The maximum daily and total dose amounts are 2 grams, with the administration route being injection. The maximum treatment period is one day. The product is authorized under the marketing authorization number 01502/0006R and is classified under the ATC code B05XA, which refers to electrolyte solutions. The sodium chloride injection is not a pediatric formulation and is used to maintain blinding in the trial.

Both treatments are prepared and packaged by Sharp Clinical Services Ltd, ensuring that the tranexamic acid and sodium chloride solutions are indistinguishable in appearance. This is achieved by using heat shrink sleeving on the ampoules, which are then labeled in accordance with EU regulations. Each treatment pack contains four 5 mL glass ampoules and is labeled with a unique pack number for identification. Detailed prescribing and administration instructions are provided within the treatment pack, and the final product is released by a qualified person to ensure compliance with trial protocols. Participant treatment packs are delivered to the hospital pharmacy for administration.

The efficacy of tranexamic acid (TXA) in the clinical trial titled "Tranexamic acid for hyperacute spontaneous IntraCerebral Haemorrhage (TICH-3)" will be assessed primarily by evaluating the effect of TXA on early death, defined as mortality occurring up to and including day 7 after the onset of **IntraCerebral Haemorrhage (ICH)**. This primary endpoint is justified by the hypothesis that TXA, as a haemostatic therapy, may improve outcomes by preventing hematoma expansion (HE), which is a common cause of early death following ICH.

Secondary efficacy assessments will focus on the effect of TXA on patient dependency six months post-ICH. The trial will utilize the modified Rankin Scale (mRS) at 90 days as a functional outcome measure, which is a standard practice in stroke-related studies. The trial is designed to determine whether TXA should be incorporated into clinical practice for the treatment of ICH, with a particular focus on its potential to reduce early mortality and long-term dependency.