Evaluation of Dexamethasone Sodium Phosphate in Acute Aneurysmal Subarachnoid Hemorrhage: A Randomized, Placebo-Controlled Study

The primary objective of this study is to analyze the impact of an anti-inflammatory treatment with **dexamethasone** in patients with acute **aneurysmal subarachnoid hemorrhage** (SAH), with or without an initial inflammatory signature in peripheral blood, compared to a placebo. This objective is clinically relevant as it aims to determine the efficacy of dexamethasone in improving outcomes for patients suffering from SAH, a condition associated with high morbidity and mortality rates.

Secondary objectives include:

• Analysis of improvement in survival rate.
• Analysis of improvement in recovery time in patients receiving dexamethasone after SAH.
• Analysis of delayed ischemic neurological deficit (DIND).
• Analysis of symptomatic vasospasm.
• Analysis of inflammation parameters.
• Evaluation of quality of life (QoL).
• Safety analysis of dexamethasone for treatment in patients suffering from SAH.

The clinical trial focuses on patients diagnosed with **aneurysmal subarachnoid hemorrhage (SAH)**. The study population includes both male and female subjects who are 18 years of age or older. Participants must have a confirmed diagnosis of aneurysmal SAH, with the onset occurring within 48 hours prior to inclusion in the study. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are required to provide written consent, either personally or through a legal representative, to partake in the study. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that only individuals with a recent diagnosis of SAH are included, allowing for the assessment of the impact of dexamethasone as an anti-inflammatory treatment compared to a placebo.

The clinical trial is designed to evaluate the impact of **dexamethasone sodium phosphate** as an anti-inflammatory treatment in patients with acute **aneurysmal subarachnoid hemorrhage** (SAH). This is a Phase III, randomized, double-blind, controlled trial comparing the effects of dexamethasone to a placebo. The trial aims to assess the combined mortality and severe disability outcomes using the modified Rankin Scale (mRS) six months post-hemorrhage, with secondary endpoints including mortality analysis at various intervals, length of ICU stay, delayed ischemic neurological deficits, and levels of inflammation parameters.

Participants will be involved in the study for a maximum treatment period of 21 days, with the overall trial expected to conclude by December 31, 2025. The trial will commence with a screening visit to confirm eligibility, which includes criteria such as age (18 years or older), written consent, and a confirmed diagnosis of aneurysmal SAH within 48 hours prior to inclusion. Following the screening, participants will be randomly assigned to receive either the dexamethasone treatment or a matching placebo, administered intravenously.

Study visits will be scheduled to monitor the participants' health and response to treatment. These visits will include assessments of clinical outcomes, laboratory tests to measure inflammation markers, and imaging studies to evaluate neurological status. Follow-up visits will occur at specified intervals, including assessments at 7, 90, and 365 days post-SAH to evaluate mortality and other secondary endpoints. The end-of-study visit will mark the completion of the participant's involvement, where final assessments will be conducted.

Participants may be withdrawn from the study early if they experience adverse events that necessitate discontinuation, if they withdraw consent, or if they do not comply with the study protocol. The trial is structured to ensure rigorous data collection and analysis, maintaining the integrity and scientific validity of the results.

The clinical trial involves the administration of **Dexa 8 mg inject JENAPHARM Injektionslösung**, a pharmaceutical product containing the active substance **dexamethasone sodium phosphate**. This medication is provided in the form of a **solution for injection** and is manufactured by MIBE GMBH ARZNEIMITTEL. The route of administration is **intravenous**, with a maximum daily dose of 24 mg and a total maximum dose of 280 mg over a treatment period of up to 21 days. The primary objective of the trial is to evaluate the impact of this anti-inflammatory treatment in patients with acute aneurysmal subarachnoid hemorrhage.

A **placebo** is used as a comparator in this study to match the Dexa 8 mg inject JENAPHARM. The placebo is designed to mimic the appearance and administration route of the active treatment, ensuring blinding of the study participants and investigators. The placebo is manufactured by mibe and is administered intravenously, similar to the active treatment. The use of a placebo allows for a controlled comparison to assess the efficacy and safety of the dexamethasone treatment.

Efficacy in this clinical trial will be assessed through a combination of primary and secondary endpoints. The primary endpoint involves the comparison of combined mortality and severe disability between study arms, evaluated using the modified Rankin Scale (mRS) six months after the occurrence of an aneurysmal subarachnoid hemorrhage (aSAH). The outcomes will be dichotomized into "favourable" (mRS 0-3) versus "unfavourable" (mRS 4-6) categories.

Secondary endpoints include several parameters: mortality analysis at 7, 90, and 365 days post-aSAH, comparison of time of death, length of ICU stay and hospitalization, occurrence of delayed ischemic neurological deficit (DIND), and symptomatic vasospasm assessed by transcranial Doppler, computed tomography scans, MR angiography, or angiography. Additionally, the level of inflammation parameters such as **C-reactive protein (CRP)**, procalcitonin (PCT), white blood cell count (WBC), and interleukin-6 (IL-6) in serum will be measured. Patient-reported outcomes will be evaluated using SF36 and EQ-ED scores at discharge and at 90, 180, and 365 days post-aSAH. The analysis of adverse events (AEs) will be conducted by examining their number, severity, and relationship to the treatment.