Evaluation of Human Plasma Proteins with ≥96% Albumin in Acute Critical Illness Requiring Intensive Care Unit Admission: A Randomized Controlled Trial

The primary objective of the Intensive Care Platform Trial (INCEPT) is to assess the effects of various **interventions** used in adults who are acutely admitted to the intensive care unit (ICU) due to acute critical illness. This trial is clinically relevant as it focuses on interventions that are commonly used but vary in practice among clinicians, potentially leading to differences in patient outcomes. By evaluating these interventions, the study aims to standardize care practices and improve patient management in the ICU setting.

The clinical trial involves a study population of **adults** aged 18 years and older who are acutely admitted to the **intensive care unit** (ICU) due to an **acute critical illness**. The trial includes both male and female participants, and it is noted that the population may include vulnerable individuals. The sponsor has not provided the total number of participants involved in the study. Participants were selected based on their acute admission to the ICU and eligibility for at least one active domain of the trial. The trial does not specify any particular lifestyle considerations such as diet, physical activity, or habits. The study aims to assess the effects of interventions commonly used in ICU settings where clinical practice may vary among healthcare providers.

The clinical trial is designed to evaluate the effects of interventions in adults with **acute critical illness** requiring admission to the intensive care unit (ICU). The trial employs a **randomized, double-blind, controlled** methodology to ensure the reliability and validity of the results. The trial is expected to commence recruitment on March 1, 2025, and conclude by December 31, 2035. Participants will be involved in the study for a maximum treatment period of 90 days, with the possibility of early termination if specific conditions arise, such as adverse reactions or withdrawal of consent.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as being an adult patient (≥18 years old) acutely admitted to the ICU and eligible for at least one active domain. Follow-up visits will be scheduled to monitor the participants' health status and response to the intervention. The end-of-study visit will assess the primary and secondary endpoints, including all-cause mortality at various intervals (30, 90, and 180 days), days alive without life support, and health-related quality of life measures.

The trial will utilize **Human Albumin** solutions for infusion, administered intravenously, with a maximum daily dose of 10 liters and a total dose not exceeding 30 liters over the treatment period. The primary outcome will vary between domains but will be selected from the secondary outcomes, which include mortality rates, days alive without life support, and cognitive function assessments. The trial is categorized as low intervention, focusing on the therapeutic usage of authorized drugs, and aims to address variations in clinical practice among healthcare providers.

The clinical trial involves the administration of two experimental medications, both of which are solutions for infusion containing **human plasma proteins** with not less than 96% **albumin**. The first medication is "Human Albumin 'CSL Behring', infusionsvæske, opløsning 5%". This pharmaceutical form is a solution for infusion, and it is administered intravenously. The maximum daily dose is 10 liters, with a total maximum dose of 30 liters over a treatment period of up to 90 days. The product is manufactured by CSL Behring GmbH and is not a pediatric formulation. The medication is authorized for use in Denmark under the marketing authorization number 35990.

The second experimental medication is "Human Albumin 'CSL Behring', infusionsvæske, opløsning 20%". Similar to the first medication, it is also a solution for infusion administered intravenously. The dosing regimen is identical, with a maximum daily dose of 10 liters and a total maximum dose of 30 liters over a 90-day treatment period. This product is also manufactured by CSL Behring GmbH and is authorized for use in Denmark with the marketing authorization number 35991. Both medications are classified under the ATC code B05AA01, indicating their categorization as albumin products.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial aims to assess the effects of these interventions in adults acutely admitted to the intensive care unit, focusing on interventions where clinical practice varies among healthcare providers.

Efficacy in the clinical trial titled "The Intensive Care Platform Trial (INCEPT)" will be assessed using a set of predefined endpoints. The primary endpoint for each domain within the trial will be selected from a list of secondary endpoints, which are part of the core outcome set defined in the core protocol. These secondary endpoints include various measures of patient outcomes, such as all-cause mortality at 30, 90, and 180 days, and days alive without life support at 30 and 90 days. Additionally, days alive out of hospital at 30 and 90 days, and days free of **delirium** at 30 days will be evaluated.

Health-related quality of life will be assessed using the EQ-5D-5L index values and EQ VAS at day 180. Cognitive function will be measured at day 180 using the Montreal Cognitive Assessment test 5-minute version, v2.1 ("Mini MoCA"). The trial will also monitor one or more domain-specific safety outcomes. These efficacy parameters will be collected and analyzed at specified timepoints, ensuring a comprehensive evaluation of the interventions used in adults acutely admitted to the intensive care unit.