Efficacy of Apixaban Versus Standard Care in Patients with Intracerebral Hemorrhage: A Randomized Controlled Trial

The primary objective of the study is to assess the **efficacy** of the strategy "Direct Oral Anticoagulant (OAC)" or "avoiding OAC with Left Atrial Appendage Closure (LAAC)" compared to "usual care (avoiding anticoagulation and LAAC)" on individual components of the net clinical benefit, mortality, dependency, and health-related quality of life in patients with **intracerebral haemorrhage**. This is clinically relevant as it aims to determine the optimal management strategy to improve patient outcomes following an intracerebral haemorrhage, a condition associated with significant morbidity and mortality.

Secondary objectives include:

• Identifying MRI cerebral biomarkers, such as brain microbleeds and superficial siderosis, that may predict the risk of future intracranial haemorrhages.
• Describing complications related to the endovascular procedure.
• Describing the overall success of the procedure.

The clinical trial involves a study population comprising **adults** over the age of 18, with no upper age limit, who have a history of paroxysmal, persistent, or long-standing non-valvular atrial fibrillation, as documented on an electrocardiogram. Participants are required to have a CHA2DS2VASc score of 2 or more, indicating a need for long-term anticoagulation, and must have experienced a spontaneous **intracerebral haemorrhage** documented by brain CT or MRI more than 30 days prior to randomization. Both male and female subjects are included, and the trial does not involve a vulnerable population. The selection criteria ensure that participants have a clinical equipoise regarding the best preventive strategy to avoid future vascular events. The sponsor has not provided information on the total number of participants. Participants are expected to be affiliated with the Sécurité Sociale. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of different strategies for managing patients with a history of **intracerebral haemorrhage** and non-valvular atrial fibrillation. This study is a randomized, controlled trial with a double-blind design, ensuring that neither the participants nor the investigators are aware of the treatment allocations. The trial aims to compare the outcomes of using direct oral anticoagulants (DOACs) or avoiding anticoagulation with left atrial appendage closure (LAAC) against usual care, which involves avoiding both anticoagulation and LAAC. The primary endpoint is a composite of fatal or life-threatening major vascular events within 24 months post-randomization. Secondary endpoints include individual components of the composite outcome, overall mortality, functional dependence, health-related quality of life, and complications of endovascular treatment.

The trial is expected to last until February 2028, with participant involvement spanning up to 24 months. The sequence of study visits begins with an inclusion visit, where eligibility is confirmed based on criteria such as age, history of atrial fibrillation, and previous intracerebral haemorrhage. Follow-up visits are scheduled to monitor the participants' health status, adherence to the treatment protocol, and to collect data on the primary and secondary endpoints. The end-of-study visit marks the conclusion of the participant's involvement, where final assessments are conducted.

Participants may be withdrawn from the study if they experience adverse events that compromise their safety, if they withdraw consent, or if they fail to comply with the study protocol. The trial's design and procedures are structured to ensure the collection of robust data while maintaining the safety and well-being of the participants throughout the study duration.

The clinical trial involves the administration of **Eliquis 2.5 mg film-coated tablets**, which contain the active substance **apixaban**. Apixaban is a chemical compound classified as an oral direct anticoagulant (AOD). The pharmaceutical form of the medication is a film-coated tablet, designed for oral use. The dosage regimen for the trial specifies a maximum daily dose of 10 mg, with the treatment period extending up to 24 months. The tablets are manufactured by Bristol-Myers Squibb/Pfizer EEIG and are authorized under the marketing authorization number EU/1/11/691/013. The administration of the medication is monitored to ensure participant compliance with the dosing schedule.

In addition to the experimental treatment, the study includes a comparator group receiving standard-of-care therapy, which involves avoiding anticoagulation and left atrial appendage closure (LAAC). This approach serves as a control to evaluate the efficacy of the experimental strategy, which includes the use of direct oral anticoagulants or avoiding anticoagulation with LAAC. The trial aims to assess the impact of these strategies on individual components of net clinical benefit, mortality, dependency, and health-related quality of life. Compliance with the treatment protocol is closely monitored to ensure the integrity of the study results.

The efficacy of the clinical trial titled "Avoid Anticoagulation After IntraCerebral Haemorrhage" will be assessed using a composite primary endpoint. This endpoint includes all fatal or life-threatening and major vascular events, specifically cardiovascular or cerebrovascular ischemic or hemorrhagic intracranial or extracranial events, occurring within 24 months after randomization. Secondary endpoints will further evaluate efficacy by examining each individual component of the composite outcome at 24 months, death from any cause at 24 months, and functional dependence scored on the modified Rankin Scale at 24 months in a shift analysis. Additionally, health-related quality of life will be measured using the EQ-5D (EuroQoL) at 24 months, and baseline small-vessel disease biomarkers on brain MRI will be assessed.

Complications of endovascular treatment will be monitored up to 30 days, and the overall success of the procedure will be evaluated at 30 days. The trial will compare the efficacy of the strategy "Direct OAC" or "avoiding OAC with LAAC" against "usual care" (avoiding anticoagulation and LAAC) in terms of net clinical benefit, mortality, dependency, and health-related quality. The trial is designed as a randomized controlled trial (RCT) to test the hypothesis that starting Direct OAC or avoiding OAC with Left Atrial Appendage Closure (LAAC) in patients with prior **intracerebral hemorrhage** and atrial fibrillation has a net clinical benefit superior to usual care. The trial will span a maximum treatment period of 24 months, with efficacy assessments scheduled at specified intervals to ensure comprehensive data collection and analysis.