Evaluation of Intravenous Omega-3 Fatty Acids in Reducing Organ Failure and Mortality in Predicted Severe Acute Pancreatitis: A Randomized Controlled Trial

The primary objective of this multicenter randomized controlled trial is to evaluate whether early intravenous administration of **Omega-3 fatty acids** can reduce the composite endpoint of new onset organ failure and/or mortality in patients with predicted severe acute pancreatitis (SAP). This is clinically relevant as SAP is associated with significant morbidity and mortality, and the potential immunomodulatory effects of Omega-3 fatty acids could offer a therapeutic benefit by decreasing inflammatory biomarkers and improving patient outcomes.

The clinical trial focuses on patients with **predicted severe acute pancreatitis**. The study population includes both male and female participants, aged 18 years and older. Participants are required to be in generally stable health, with the exception of their acute pancreatitis condition. The sponsor has not provided the total number of participants involved in the trial. Selection criteria for the trial population include individuals experiencing their first episode of acute pancreatitis, diagnosed within 24 hours, and less than 72 hours after the onset of symptoms. Participants must be able to comprehend the study procedures and provide informed consent, either personally or through a legal representative. The trial does not involve a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted. Key inclusion criteria involve a diagnosis of acute pancreatitis with specific clinical markers, such as an APACHE-II score above 7, a Modified Glasgow score above 2, or a CRP level exceeding 150 mg/L.

The clinical trial is designed to evaluate the efficacy of early intravenous administration of **omega-3 fatty acids** in reducing the composite endpoint of new onset organ failure and mortality in patients with predicted severe acute pancreatitis. This is a multicenter, randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is expected to run until January 31, 2026, with recruitment having commenced on September 19, 2023. Participants will be randomly assigned to receive either the omega-3 fatty acid infusion or standard medical care, with the primary endpoint being assessed after a 180-day study period.

Study visits are structured to include an initial screening visit, where eligibility is confirmed based on criteria such as age, diagnosis of acute pancreatitis, and ability to provide informed consent. Follow-up visits will occur at specified intervals to monitor the participants' health status, adverse events, and response to treatment. The end-of-study visit will conclude the participant's involvement, with final assessments of the primary and secondary endpoints, including mortality rates, new onset organ failure, and length of hospital and ICU stays.

Participant involvement is expected to last for the duration of the 180-day study period, unless early termination is warranted. Conditions for early termination include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial aims to provide robust data on the potential benefits of omega-3 fatty acids in managing severe acute pancreatitis, contributing to improved clinical outcomes and healthcare practices.

The clinical trial involves the administration of **Omegaven**, an emulsion for infusion, as the experimental medication. Omegaven is composed of **glycerol**, **highly refined fish oil**, and **purified egg phospholipids**. The pharmaceutical form of Omegaven is an emulsion specifically designed for intravenous infusion. The dosage is calculated based on the participant's body weight, with a maximum daily dose of 2 milliliters per kilogram and a total maximum dose of 14 milliliters per kilogram over the treatment period. The maximum treatment duration is set at 7 days. The administration route is strictly intravenous, ensuring direct delivery into the bloodstream for optimal efficacy. The product is manufactured by Fresenius Kabi Deutschland GmbH and is not a pediatric formulation.

In this study, Omegaven is compared against standard medical care, which serves as the non-experimental treatment. The standard medical care acts as the comparator treatment to evaluate the efficacy of early intravenous administration of Omega-3 fatty acids in reducing the composite endpoint of new onset organ failure and/or mortality in patients with predicted severe acute pancreatitis (SAP). The trial does not involve the use of a placebo. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol and to accurately assess the outcomes related to the experimental treatment.

Efficacy in the clinical trial titled "Pancreatitis and early omega-3-fatty acid infusion for reduction of organ failure and mortality: a multicenter randomized controlled trial (PLANCTON)" will be assessed using a composite primary endpoint. This endpoint includes the new onset of organ failure, specifically cardiovascular, pulmonary, or renal, and mortality. The new onset of organ failure is defined as organ failure that was not present at the time of randomization and will be evaluated according to the modified Marshall score. The primary endpoint will be evaluated after a 180-day study period.

Secondary endpoints will include the individual components of the primary outcome, such as mortality during follow-up (14-day, 28-day, or in-hospital mortality), new onset organ failure during follow-up, and infectious complications like pneumonia, urinary tract infections, wound infections, or infected (peri-) pancreatic necrosis. Additional secondary endpoints will assess the need for surgical, endoscopic, or radiologic interventions, the levels of **C-reactive protein (CRP)** on days 0, 1, 2, 3, 5, and 7, and the total length of hospital and ICU stays. These parameters will be measured and collected at specified time points to evaluate the efficacy of early intravenous administration of Omega-3 fatty acids compared to standard medical care in patients with predicted severe acute pancreatitis (SAP).