Efficacy and Safety of Statin Continuation vs. Discontinuation in Patients with Spontaneous Lobar Intracerebral Hemorrhage: A Randomized Controlled Trial

The primary objective of this study is to evaluate the **efficacy** and **safety** of continuing versus discontinuing statin therapy in patients with spontaneous lobar intracerebral hemorrhage (ICH) over a 24-month follow-up period. The study aims to determine the impact of statin discontinuation on the risk of recurrent symptomatic ICH, hypothesizing that discontinuation may reduce this risk. Additionally, the study seeks to assess the effects of statin discontinuation on the occurrence of major adverse cardiac and cerebrovascular events (MACCE), including symptomatic ischemic stroke, myocardial infarction, arterial occlusive disease, revascularization procedures, and vascular death, with the hypothesis that discontinuation may increase the risk of MACCE.

Secondary objectives include: - Examining quality of life, functional, and cognitive outcomes in participants who continue versus discontinue statins, using repeated assessments of the EQ-5D quality of life questionnaire, modified Rankin Scale (mRS), and Telephone Montreal Cognitive Assessment (T-MoCA) at various intervals. The study hypothesizes that discontinuing statins may lead to better outcomes due to a reduced risk of ICH recurrence. - Investigating whether the presence of APOE ε4 and APOE ε2 genotypes modifies the effects of statins on the risk of recurrent ICH, proposing that these genotypes may increase the risk of recurrence with continued statin therapy. If confirmed, avoiding statins in this subset of patients may be beneficial in reducing recurrence risk.

The clinical trial involves a total of **1276 participants** who are being studied to assess the effects of statin continuation versus discontinuation on the risk of recurrent **intracerebral hemorrhage (ICH)** and major adverse cardiac and cerebrovascular events. The study population includes both male and female subjects aged **50 years and older**. Participants were selected based on the confirmation of spontaneous lobar ICH via CT or MRI scan, and they must have been taking a statin drug at the onset of the qualifying ICH. Randomization is required within seven days of the onset of the qualifying ICH, and participants or their legally authorized representatives must agree to the randomization process after consulting with their physicians. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria. The sponsor has not provided additional information regarding the general health status or specific lifestyle habits of the participants.

The clinical trial is designed to evaluate the **efficacy** and **safety** of continuing versus discontinuing statin therapy in patients with spontaneous lobar intracerebral hemorrhage (ICH). This trial employs a randomized, double-blind, controlled design to ensure unbiased results. Participants will be randomly assigned to either continue or discontinue their statin medication, with the primary objective of assessing the impact on the risk of recurrent symptomatic ICH over a 24-month follow-up period. The trial will also evaluate the occurrence of major adverse cardiac and cerebrovascular events (MACCE) as a primary safety endpoint.

The trial is expected to last until September 2029, with recruitment having commenced in September 2022. Participants will be involved in the study for a maximum of 24 months. The study includes several key visits: an initial screening visit to confirm eligibility, randomization within 7 days of the qualifying ICH, and regular follow-up visits to monitor health outcomes and adherence to the assigned treatment. The end-of-study visit will conclude the participant's involvement, assessing final outcomes and collecting data on any adverse events.

Inclusion criteria require participants to be aged 50 years or older, have a confirmed spontaneous lobar ICH via CT or MRI, and have been on statin therapy at the onset of the ICH. Randomization must occur within 7 days of the ICH onset. Participants or their legally authorized representatives must consent to randomization after consulting with their prescribing physicians. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety.

The clinical trial involves the administration of **Simvastatin** and **Atorvastatin**, both of which are utilized in the form of film-coated tablets. **Simvastatin** is provided in dosages of 10 mg, 20 mg, and 40 mg, while **Atorvastatin** is available in dosages of 10 mg, 20 mg, 40 mg, and 60 mg. These medications are administered orally. The maximum daily dose for each medication is 80 mg, and the treatment period extends up to 96 weeks. The active substances in both medications are of chemical origin, and the products are manufactured by Laboratorios Normon, S.A. in Spain. The trial aims to evaluate the effects of continuing versus discontinuing statin therapy in patients with intracerebral hemorrhage.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of the experimental medications, **Simvastatin** and **Atorvastatin**. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial's objective is to assess the efficacy and safety of these statins in reducing the risk of intracerebral hemorrhage recurrence and major adverse cardiac and cerebrovascular events over a 24-month follow-up period.

The efficacy of the clinical trial will be assessed by evaluating the impact of continuing versus discontinuing statins on the risk of recurrent symptomatic **intracerebral hemorrhage (ICH)** over a 24-month follow-up period. The primary efficacy endpoint is the risk of recurrent symptomatic ICH. Secondary endpoints include quality of life, cognitive and functional outcomes, which will be measured using the EQ-5D questionnaire, the modified Rankin Scale (mRS), and the Telephone Montreal Cognitive Assessment (T-MoCA). Additionally, the trial will examine the effects of APOE ε4 and ε2 genotypes on the risk of recurrent ICH.