Intraperitoneal fosfomycin, metronidazole and molgramostim for patients with multi‑quadrant peritonitis undergoing abdominal surgery: placebo‑controlled trial

The primary objective of this study is to evaluate the efficacy of **intraperitoneal** administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), metronidazole, and fosfomycin in optimizing the treatment of patients with multi-quadrant **peritonitis** undergoing abdominal surgery. This is clinically relevant as peritonitis is a severe inflammatory condition that can lead to significant morbidity and mortality if not effectively managed. The study aims to determine whether this combination therapy can improve patient outcomes by enhancing the resolution of infection and reducing complications associated with peritonitis.

The clinical trial focuses on patients diagnosed with **peritonitis**, specifically those with multiquadrant involvement due to a lesion in the large intestine. The study population includes both male and female participants aged 18 years and older. The trial does not involve a vulnerable population. Participants are selected based on their need for surgical intervention with findings of peritonitis affecting two or more quadrants. The sponsor has not provided information regarding the total number of participants. No specific lifestyle considerations such as diet or physical activity are highlighted in the trial details. The selection criteria ensure that the study population is representative of individuals who are undergoing surgical treatment for this condition.

The clinical trial is designed to evaluate the efficacy and safety of **intraperitoneal** administration of **fosfomycin**, **metronidazole**, and **molgramostim** in patients with multi-quadrant **peritonitis** undergoing abdominal surgery. This is a randomized, placebo-controlled trial with a double-blind design to ensure unbiased results. The trial is set to commence recruitment on September 1, 2025, and is expected to conclude by April 1, 2030. The study will involve a series of visits, starting with an inclusion visit where participants will be screened based on the principal inclusion criteria, which require patients to be aged 18 or older and undergoing surgical intervention with findings of peritonitis involving at least two quadrants of the large intestine.

Participants will be randomly assigned to receive either the active treatment or a placebo. The trial will include follow-up visits to monitor the primary and secondary endpoints. The primary endpoints focus on changes in IL-6 levels in peritoneal dialysate and the Quality of Recovery-15 (QoR-15) score. Secondary endpoints include macrophage phagocytosis assays on peripheral blood mononuclear cells (PBMCs), changes in cytokine levels in peripheral blood and peritoneal dialysate, and various blood values such as hematology, potassium, sodium, C-reactive protein (CRP), albumin, and creatinine.

The expected duration of participant involvement is up to one day, as the maximum treatment period is limited to a single day. Conditions that may lead to early termination from the study include adverse reactions to the treatment or withdrawal of consent by the participant. The trial aims to optimize treatment strategies for patients with secondary peritonitis by assessing the translational and clinical outcomes of the intraperitoneal application of the investigational drugs.

The clinical trial involves the administration of several treatments to evaluate their efficacy in patients with multi-quadrant peritonitis undergoing abdominal surgery. The experimental medication **Fosfomycin** is provided as a solution for infusion under the product name "Fosfomycin 'Infectopharm', pulver til infusionsvæske, opløsning 40 mg/ml." It is administered via intra-abdominal use. The maximum daily dose is 4 grams, with a total treatment period of one day. Fosfomycin is a chemical substance, and its administration is monitored to ensure compliance with the dosing schedule.

Another experimental treatment is **Metronidazole**, marketed as "Metronidazol 'Baxter' Viaflo, infusionsvæske, opløsning." This medication is also a solution for infusion and is administered intra-abdominally. The maximum daily dose is 500 milligrams, with a treatment duration of one day. Metronidazole is a chemical substance, and participant adherence to the dosing regimen is closely monitored.

The trial also includes the administration of **Molgramostim**, known commercially as "Repomol." This is an intraperitoneal solution, administered via intra-abdominal use. The maximum daily dose is 50 micrograms, with a treatment period of one day. Molgramostim is a protein-based substance, and its administration is carefully monitored to ensure participant compliance.

As a non-experimental treatment, **Sodium Chloride** is used in the form of "Saline Solution Basi 9 mg/ml solution for infusion." This solution is administered intra-abdominally, with a maximum daily dose of 500 milliliters over a one-day period. Sodium chloride serves as a standard-of-care therapy and is a chemical substance. Its administration is monitored to ensure proper dosing and participant adherence.

Efficacy in this clinical trial will be assessed through a combination of primary and secondary endpoints. The primary translational endpoint is the change in **IL-6** levels in peritoneal dialysate, while the primary clinical endpoint is the change in the Quality of Recovery-15 (QoR-15) score. Secondary endpoints include a macrophage phagocytosis assay on peripheral blood mononuclear cells (PBMCs), changes in cytokine levels in peripheral blood (including **TNF-α**, **IL-1β**, **IL-6**, **IL-8**, **IL-10**, **MCP-1**, **GM-CSF**), and changes in various blood values such as hematology, potassium (K+), sodium (Na+), C-reactive protein (CRP), albumin, and creatinine (including estimated glomerular filtration rate, eGFR). Additionally, changes in cytokine levels in peritoneal dialysate (including **TNF-α**, **IL-1β**, **IL-8**, **IL-10**, **MCP-1**, **GM-CSF**) will be evaluated.

The trial is designed to investigate the efficacy of intraperitoneal administration of GM-CSF, metronidazole, and fosfomycin in optimizing treatment for patients with multiquadrant peritonitis. The efficacy parameters will be measured and collected at specified timepoints throughout the trial, using validated laboratory tests and patient-reported outcomes. The analysis will focus on the changes in the specified biomarkers and clinical scores to determine the treatment's impact on the disease condition.