Randomized Study on Immunoglobulin A, G, and M Infusion in Sepsis and Peritonitis Patients Post-Infectious Source Control

The primary objective of this study is to evaluate the **change in multiple organ failure (MOF) score** from baseline to day 7 after source control in patients with peritonitis. This is clinically relevant as it assesses the efficacy of personalized medicine with Pentaglobin® in managing organ dysfunction, which is a critical aspect of treatment in conditions such as **sepsis** and secondary or quaternary peritonitis.

Secondary objectives include:

• Assessing mortality rates within 28 days and 90 days.
• Evaluating the change in MOF score from baseline to day 5.
• Determining the incidence of multi-organ failure, defined as more than 4 MOF points, on day 7.

The clinical trial involves participants diagnosed with **sepsis** or secondary or quaternary peritonitis. The study population includes both male and female subjects, with an age range encompassing adults and the elderly. The trial specifically targets a vulnerable population, as indicated by the inclusion of individuals with severe health conditions. The sponsor has not provided the total number of participants. Selection criteria for the trial population include the presence of sepsis and/or septic shock, a Sequential Organ Failure Assessment (SOFA) score of 8 or higher, and an interleukin-6 (IL-6) concentration of at least 1000 pg/ml. Participants must have undergone source control within six hours of indication and commenced antibiotic therapy within 12 hours of admission to the intensive care unit. The trial does not specify particular lifestyle considerations such as diet or physical activity. Informed consent is required from the patient or their legal representative.

The clinical trial is a **randomized**, controlled study designed to evaluate the efficacy of Pentaglobin in patients with **sepsis** and secondary or quaternary **peritonitis**. The trial is conducted in a double-blind manner to ensure unbiased results. The primary objective is to assess the change in the multiple organ failure (MOF) score from baseline to day 7 after source control. Secondary endpoints include mortality rates within 28 and 90 days, as well as changes in the MOF score from baseline to day 5 and the presence of multi-organ failure on day 7.

The trial is expected to run until September 30, 2027, with recruitment having started on November 1, 2017. Participants will be involved in the study for a maximum treatment period of 5 days, with the possibility of early termination if specific conditions arise, such as adverse reactions or withdrawal of consent. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as a SOFA score of ≥8 and IL-6 concentration of ≥1000 pg/ml, followed by regular follow-up visits to monitor the patient's condition and response to treatment. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any remaining health concerns are addressed.

Participants will receive the investigational product, Pentaglobin, administered intravenously, with a maximum daily dose of 7 milliliters per kilogram and a total dose not exceeding 35 milliliters per kilogram. The trial is conducted under strict ethical guidelines, with informed consent obtained from all participants or their legal representatives. The study is authorized in Germany and Austria, with Biotest Pharma GmbH as the sponsor. The trial's design and methodology adhere to rigorous scientific standards to ensure the reliability and validity of the results.

The clinical trial involves the administration of **Pentaglobin 50 g/l** solution for infusion, which is an experimental medication containing **immunoglobulin A**, **immunoglobulin G**, and **immunoglobulin M**. This pharmaceutical form is a solution for infusion, intended for **intravenous use**. The dosage is calculated based on the participant's body weight, with a maximum daily dose of 7 milliliters per kilogram and a total maximum dose of 35 milliliters per kilogram over the treatment period. The maximum treatment period is 5 days. The active substances are derived from blood and are structurally diverse, with **immunoglobulin G** being classified as a protein of other origin. The product is manufactured by Biotest Pharma GmbH and is authorized for use in Austria.

Additionally, the study utilizes **Pentaglobin 50 mg/ml** solution for infusion, which also contains the same active substances: **immunoglobulin A**, **immunoglobulin G**, and **immunoglobulin M**. This formulation is similarly administered intravenously, with the same dosing regimen as the 50 g/l solution. The product is also manufactured by Biotest Pharma GmbH and is authorized for use in Germany. Both formulations are not pediatric and are not classified as orphan drugs. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed primarily through the change in the **multiple organ failure (MOF) score**. This score is determined by evaluating the function of the lungs, heart, kidneys, liver, and blood. The primary endpoint is the change in the MOF score from baseline to day 7 after source control in patients with peritonitis. Secondary endpoints include mortality rates within 28 and 90 days, change in MOF score from baseline to day 5, and the presence of multi-organ failure, defined as more than 4 MOF points, on day 7.