Evaluation of Acetylsalicylic Acid and Clopidogrel Monotherapy for Secondary Prevention in Intracerebral Hemorrhage Survivors: A Randomized Controlled Trial

The primary objective of the study is to evaluate whether initiating **oral antiplatelet drug** monotherapy is superior to avoiding such drugs, alongside standard care, in prolonging the time to the first major adverse cardiovascular or cerebrovascular events (MACE) in survivors of stroke due to **intracerebral haemorrhage**. This is clinically relevant as it addresses the potential benefits of antiplatelet therapy in reducing the risk of recurrent cardiovascular events in this patient population.

Secondary objectives include:

• Determining the effects of oral antiplatelet drug monotherapy on ischaemic MACE, assessing its efficacy.
• Evaluating the impact on haemorrhagic MACE, focusing on safety.
• Assessing the effects on individual components of MACE.
• Investigating the effects on all MACE, including ischaemic and haemorrhagic, in clinically important sub-groups.
• Examining the impact on non-cardiovascular death.
• Exploring the generalisability of the effect on the primary outcome across different countries.

The clinical trial involves a total of **3792 participants** who have experienced a stroke due to **intracerebral haemorrhage**. The study population includes both male and female subjects, aged 18 years and older, who have been diagnosed with intracerebral haemorrhage through brain imaging. Participants were selected based on the availability of a radiological text report of the brain imaging study that first diagnosed the condition, and consent was obtained from the participant or their representative if the participant lacked mental capacity. The trial includes a vulnerable population, and the participants are survivors of stroke due to intracerebral haemorrhage. The study does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that the participants are representative of the general population affected by this medical condition.

The clinical trial is designed to evaluate the efficacy of **antiplatelet therapy** in survivors of stroke due to **intracerebral haemorrhage**. This is a randomized, double-blind, controlled trial with an estimated duration from April 2025 to April 2029. Participants will be randomly assigned to receive either **acetylsalicylic acid** or **clopidogrel** as monotherapy, or to avoid antiplatelet drugs, in addition to standard care. The primary objective is to determine if starting oral antiplatelet drug monotherapy is superior to avoiding antiplatelet drugs in increasing the time to the first major adverse cardiovascular or cerebrovascular events (MACE).

The trial will commence with a screening visit to confirm eligibility, which includes a diagnosis of stroke due to **intracerebral haemorrhage** via brain imaging, age of at least 18 years, and consent from the participant or their representative. Following randomization, participants will undergo regular follow-up visits to monitor for the occurrence of MACE, which includes hospitalization due to stroke or myocardial infarction, or cardiovascular death. Secondary endpoints include the evaluation of ischaemic and haemorrhagic MACE, non-cardiovascular death, and non-hospitalized major adverse events.

Participants are expected to be involved in the study for a maximum treatment period of 60 days, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. The trial is categorized as a low intervention phase IV study, ensuring minimal risk to participants while providing valuable data on the safety and efficacy of antiplatelet therapy in this patient population.

The clinical trial involves the administration of **Acetylsalicylic Acid** in the form of "Acetylsalicylzuur Aurobindo cardio 80 mg, tabletten." This medication is presented as a **tablet** and is intended for **oral use**. The active substance, acetylsalicylic acid, is of chemical origin. The maximum daily dose is 80 mg, with a total maximum dose of 134,400 mg over a treatment period of 60 days. The medication is part of an antiplatelet therapy regimen, and its administration is monitored to ensure compliance with the dosing schedule.

Another experimental medication used in the trial is "Clopidogrel Accord 75 mg filmomhulde tabletten," which contains the active substance **Clopidogrel**. This medication is provided as a **film-coated tablet** and is also administered **orally**. The chemical origin of clopidogrel is noted, and the maximum daily dose is set at 75 mg, with a total maximum dose of 126,000 mg over a 60-day treatment period. Similar to acetylsalicylic acid, clopidogrel is used as part of an antiplatelet therapy strategy, and participant adherence to the dosing regimen is closely monitored.

Both medications are utilized in the context of the trial to evaluate their efficacy in increasing the time to first major adverse cardiovascular or cerebrovascular events in survivors of stroke due to intracerebral hemorrhage. The trial does not include any non-experimental treatments such as placebo or comparator treatments, as the focus is on the monotherapy of these antiplatelet agents.

The efficacy of the clinical trial titled "Antiplatelet Secondary Prevention International Randomised study after INtracerebral haemorrhaGe" (ASPIRING) will be assessed by evaluating the time to the first major adverse cardiovascular or cerebrovascular events (MACE) in survivors of stroke due to **intracerebral haemorrhage** (ICH). The primary endpoint for efficacy assessment is the first occurrence of any MACE, which includes hospitalisation due to stroke or myocardial infarction, or cardiovascular death. Secondary endpoints include the evaluation of major adverse cardiovascular events condition groups (ischaemic MACE and haemorrhagic MACE), MACE components (stroke, myocardial infarction, and cardiovascular death), non-cardiovascular death, and non-hospitalized major adverse cardiovascular or cerebrovascular events.