Evaluation of Intravenous Dornase Alfa for Reducing Systemic Inflammation in Acute Ischemic Stroke Patients

The primary objective of the study is to evaluate the efficacy of **DNase 1** administration in reducing the systemic immune response in patients following an acute ischemic stroke. This is measured by the concentration of blood interleukin-1 beta at 24±6 hours after symptom onset, compared to a control treatment. This objective is clinically relevant as it aims to address the inflammatory response associated with ischemic stroke, which can exacerbate neurological damage and affect recovery outcomes.

Secondary objectives include testing the hypothesis that **DNase 1** treatment reduces post-stroke infections, improves functional outcomes as assessed by the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS), and induces positive changes in immunological parameters without compromising patient safety. These objectives are significant as they explore the broader impact of **DNase 1** on patient recovery and safety, potentially offering a comprehensive therapeutic approach to managing post-stroke complications.

The clinical trial focuses on the **reduction of systemic inflammation** following an acute ischemic stroke through the administration of DNase. The study population includes both male and female participants, aged 18 years and older, who have experienced an acute ischemic stroke with symptom onset to investigational drug application of less than 12 hours. Participants are required to have a National Institutes of Health Stroke Scale (NIHSS) score of 10 or higher at admission. The trial includes a vulnerable population, although specific details regarding the total number of participants and their general health status are not provided by the sponsor. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data. The selection criteria emphasize the urgency and severity of the stroke, ensuring that participants are those who can potentially benefit from the investigational treatment within a critical time window.

The clinical trial is designed to evaluate the efficacy of **dornase alfa** in reducing systemic inflammation following an acute ischemic stroke. This study is a **randomized**, **double-blind**, and **controlled** trial, aiming to compare the effects of the investigational drug against a placebo. The primary objective is to assess the reduction in systemic immune response, specifically measuring blood interleukin-1 beta concentration within 24±6 hours after symptom onset. The trial is expected to commence recruitment on January 1, 2025, and conclude by December 31, 2026.

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), suspected acute ischemic stroke with symptom onset to drug application within 12 hours, and a National Institutes of Health Stroke Scale (NIHSS) score of ≥10 at admission. Following randomization, participants will receive either the investigational drug or placebo via intravenous administration. The study includes follow-up visits to monitor the primary endpoint and any secondary outcomes, with data collection focusing on the interleukin-1 beta levels and other relevant clinical parameters.

The expected duration of participant involvement is approximately 24 hours post-symptom onset, with the possibility of early termination if adverse events occur or if the participant withdraws consent. The trial will employ a mixed linear regression model to analyze the primary endpoint, ensuring adherence to the intention-to-treat principle. Secondary endpoints will be evaluated using descriptive statistics, with exploratory analysis conducted to assess differences between the study arms. The trial is categorized as a Phase 4 study, indicating its focus on post-marketing surveillance and further evaluation of the drug's therapeutic effects.

The clinical trial involves the administration of **Dornase Alfa**, marketed under the name Pulmozyme 2.500 E./2.5 ml, which is formulated as a **nebuliser solution**. This experimental medication is utilized in the study to evaluate its efficacy in reducing systemic inflammation following an acute ischemic stroke. The active substance, Dornase Alfa, is a protein of non-chemical origin, specifically categorized under the ATC code R05CB13. The solution is administered via **intravenous bolus use**, with a maximum daily and total dose of 100 mg. The treatment period is limited to one day. The Dornase Alfa solution is provided by Roche Pharma AG and is authorized for use in Germany.

In addition to the experimental treatment, the study employs **Sodium Chloride** as a comparator treatment. This is provided in the form of an **isotonic saline solution** for injection, known as Isotonische Kochsalzlösung. The solution is administered intravenously, with a maximum daily and total dose of 100 ml, also limited to a one-day treatment period. Sodium Chloride serves as a standard-of-care therapy, ensuring a controlled environment for evaluating the effects of Dornase Alfa. The isotonic saline solution is manufactured by Fresenius Kabi Deutschland GmbH and is authorized for use in Germany.

Efficacy in the clinical trial titled "Reduction of SystemiC Inflammation after ischemic stroke by intravenous DNase administration (ReSCInD)" will be assessed primarily through the measurement of **interleukin-1 beta (IL-1 β)** concentration in the blood. This primary endpoint will be evaluated within 24±6 hours of symptom onset in patients who have experienced an acute ischemic stroke. The analysis will be conducted on the full analysis set, adhering as closely as possible to the intention-to-treat principle. A mixed linear regression model will be employed, with the IL-1 β level at 24±6 hours as the dependent variable, the randomized group and the IL-1 β level at baseline as independent variables, and the center as a random effect. Logarithmization is planned due to the skewness of IL-1 β data.

Secondary endpoints will be summarized using descriptive statistics, and differences between the two study arms will be analyzed exploratively according to their scale level. The trial aims to test the hypothesis that DNase 1 administration leads to a reduction of systemic immune response, as indicated by the primary endpoint, compared with control treatment. The trial is categorized as a Phase IV study, with an estimated end date of December 31, 2026.