Randomized Double-Blind Multicenter Trial of Caspofungin Versus Placebo in the Treatment of Yeast Intra-Abdominal Infection in ICU Patients

The primary objective of this study is to evaluate the **decrease of failure rate** at 28 days after the initiation of treatment in an intention-to-treat (ITT) analysis for patients with yeast intra-abdominal infection, including peritonitis. This is clinically relevant as it aims to improve patient outcomes by reducing the incidence of treatment failure, which is critical in managing severe infections in intensive care unit (ICU) settings.

Secondary objectives include:

• Decreased crude 28 and 90-day mortality on ITT and per-protocol (PP) analysis, which is important for assessing long-term survival benefits.
• Increased success rate at the end of treatment on ITT and PP analysis, providing insights into the efficacy of the treatment regimen.
• Decreased serum **ß-D-glucan** concentration at the end of treatment, which serves as a biomarker for fungal infection resolution.
• Subgroup analysis for 28-day mortality, comparing community-acquired versus healthcare-associated infections, timing of antifungal therapy (empiric or documented), **C. albicans** versus **C. non-albicans**, and septic shock versus no shock, to identify specific patient populations that may benefit more from the treatment.

The clinical trial focuses on participants diagnosed with **yeast intra-abdominal infection**, specifically peritonitis. The study population includes both male and female subjects, aged 18 years and older, who are covered by national health insurance. Participants are required to have been admitted to the ICU following surgery for intra-abdominal infection, with either suspected or documented intra-abdominal candidiasis. The trial involves a vulnerable population, as indicated by the inclusion of ICU patients. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data. Key inclusion criteria include a Peritonitis score of 3 or higher or positive direct examination or culture of peritoneal fluid collected intraoperatively, along with written and signed informed consent.

The clinical trial is a **randomized**, **double-blind**, controlled study designed to evaluate the efficacy of **caspofungin** compared to placebo in the treatment of **yeast intra-abdominal infection**, specifically peritonitis, in patients admitted to the intensive care unit (ICU). The primary objective is to decrease the failure rate at 28 days after the initiation of treatment, with secondary endpoints including 28 and 90-day mortality, success rate at the end of treatment, and the slope of β-D-glucan concentrations. The trial is expected to run from January 2020 to April 2026, with an estimated duration of participant involvement of up to 8 weeks.

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), ICU admission post-surgery for intra-abdominal infection, and informed consent. Follow-up visits will be scheduled to monitor treatment response and safety, with assessments including clinical evaluations and laboratory tests. The end-of-study visit will occur at the conclusion of the treatment period to evaluate the primary and secondary endpoints.

Participants may be withdrawn from the study early if they experience adverse events, withdraw consent, or if the investigator deems it necessary for safety reasons. The trial will utilize **intravenous** administration of the investigational product, with a maximum daily dose of 70 mg for caspofungin and 0.9% for sodium chloride, the latter serving as a placebo. The study is not classified as low intervention and is categorized as a phase III therapeutic confirmatory trial.

The clinical trial involves the administration of **CANCIDAS**, which contains the active substance **caspofungin**. This medication is provided in two formulations: a 70 mg and a 50 mg powder for concentrate for solution for infusion. The pharmaceutical form is a solution for infusion, and the route of administration is **intravenous use**. The maximum daily dose for the 70 mg formulation is 70 mg, with a total maximum dose of 560 mg over a treatment period of up to 8 days. For the 50 mg formulation, the maximum daily dose is 50 mg, with a total maximum dose of 420 mg over the same treatment period. The medication is manufactured by Merck Sharp & Dohme B.V. and is not a paediatric formulation. Participant compliance with the dosing schedule will be monitored throughout the trial.

In addition to the experimental treatment, the study utilizes **Sodium Chloride B Braun 0.9%** as a comparator treatment. This solution for injection contains the active substance **sodium chloride** and is administered via intravenous use. The maximum daily and total dose is 0.9%, consistent with its role as a solvent and diluting agent. This product is manufactured by B.Braun Melsungen AG and is also not a paediatric formulation. The use of sodium chloride serves as a standard-of-care therapy to ensure the safety and efficacy of the experimental treatment are accurately assessed.

The efficacy of the clinical trial will be assessed using several key endpoints. The primary endpoint is the 28-day failure rate after the beginning of treatment. Secondary endpoints include 28 and 90-day mortality, success rate at the end of treatment, the slope of **β-D-glucan** concentrations, and 28-day mortality for subgroup analysis. These endpoints will provide a comprehensive evaluation of the treatment's effectiveness in reducing the failure rate and improving survival outcomes.

The trial is designed as a prospective multicenter randomized double-blind study comparing **caspofungin** to placebo for the treatment of yeast intra-abdominal infection in ICU patients. The main objective is to decrease the failure rate at 28 days after the beginning of treatment, assessed through an intention-to-treat (ITT) analysis. The efficacy parameters will be measured and collected at specified timepoints, including the end of treatment and at 28 and 90 days post-treatment initiation. The analysis will involve validated laboratory tests and clinical assessments to ensure accurate and reliable data collection.