Evaluation of Anakinra for Efficacy and Safety in Non-COVID-19 Acute Respiratory Distress Syndrome (ARDS) Patients

The primary objective of this study is to evaluate the number of **ventilation-free days** in patients with acute respiratory distress syndrome (ARDS) unrelated to COVID-19. This measure is clinically relevant as it reflects the patient's ability to sustain adequate respiration without mechanical support, which is a critical factor in recovery and overall prognosis in ARDS management.

The secondary objectives of the study include assessing various clinical outcomes and physiological parameters:

• 28-day mortality, ICU mortality, and in-hospital mortality rates.
• Improvement in the PaO2/FiO2 ratio, driving pressure, peak pressure, and plateau pressure from day 0 to day 28.
• Days free from multi-organ damage, as calculated by the Sequential Organ Failure Assessment (SOFA) score, and days free from renal function replacement therapy.
• Peak levels of creatininemia, AST/ALT/bilirubin, and days free from vasoactive support.
• Duration of inpatient days post-ICU discharge, ICU inpatient days, and total intrahospital inpatient days.
• Cumulative dose of corticosteroids administered.

These secondary objectives aim to provide a comprehensive evaluation of the treatment's impact on patient outcomes and organ function, offering insights into the broader clinical benefits and safety profile of anakinra in the management of non-COVID-19 related ARDS.

The clinical trial focuses on evaluating ventilation-free days in patients diagnosed with **acute respiratory distress syndrome (ARDS)**. The study population comprises adults aged 18 years and older, including both male and female participants. Participants are required to be admitted to the ICU with a diagnosis of moderate to severe ARDS within 48 hours, necessitating intubation and mechanical ventilation. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Key lifestyle considerations such as diet, physical activity, or habits are not specified. The selection criteria include a negative COVID-19 swab and adherence to the Berlin clinical criteria for ARDS, among other clinical-laboratory profiles. The trial population was selected based on these specific medical and clinical criteria, ensuring a focused study group for the evaluation of the trial's main objective.

The clinical trial is designed to evaluate the **efficacy** and safety of **anakinra** in patients with acute respiratory distress syndrome (ARDS) unrelated to COVID-19. This is a Phase 4, randomized, double-blind, controlled study. The trial aims to assess the primary endpoint of ventilation-free days, with secondary endpoints including 28-day mortality, ICU mortality, in-hospital mortality, and improvements in various respiratory parameters. The study is expected to run from May 4, 2023, to May 3, 2025, with a maximum treatment period of 14 days for each participant.

Participants will be required to attend several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, ARDS diagnosis, and negative COVID-19 status. Follow-up visits will be scheduled to monitor the participants' health status and collect data on the study endpoints. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any remaining health concerns are addressed.

The expected length of participant involvement is up to 14 days, with conditions for early termination including withdrawal of consent, adverse events, or any situation where continued participation is deemed unsafe by the investigator. The study will utilize **Kineret** 100 mg/0.67 ml solution for injection, administered subcutaneously, with a maximum daily dose of 100 mg and a total dose not exceeding 1400 mg over the treatment period. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves the administration of **Kineret**, a pharmaceutical product containing the active substance **anakinra**. Kineret is formulated as a **solution for injection** in a pre-filled syringe, with a concentration of 100 mg/0.67 ml. The medication is administered via **subcutaneous injection**. The dosing regimen for this trial specifies a maximum daily dose of 100 mg, with a total maximum dose of 1400 mg over a treatment period of 14 days. The product is manufactured by Swedish Orphan Biovitrum AB (Publ) and is not a pediatric formulation. The active substance, anakinra, is a protein of non-human origin, classified under the ATC code L04AC03.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on evaluating the efficacy and safety of anakinra in patients with non-COVID-19 related acute respiratory distress syndrome (ARDS). Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The primary objective of the study is to assess the number of ventilation-free days in the patient population.

The efficacy of anakinra in the treatment of non-COVID-19 related **Acute Respiratory Distress Syndrome (ARDS)** will be assessed in this clinical trial. The primary endpoint for evaluating efficacy is the number of ventilation-free days. Secondary endpoints include 28-day mortality, ICU mortality, in-hospital mortality, and improvements in the PaO2/FiO2 ratio, with measurements taken at day 0 and day 28. Additional secondary endpoints involve the reduction of driving pressure, peak pressure, and plateau pressure, also measured at day 0 and day 28. The trial will also assess days free from multi-organ damage, calculated using the Sequential Organ Failure Assessment (SOFA) score, with a score of less than 2 at day 28 indicating efficacy.