Evaluation of Early Versus Delayed Supplementary Parenteral Nutrition on Postoperative Nosocomial Infection Risk in Major Emergency Abdominal Surgery Patients

The primary objective of this study is to compare the effect of **early** versus postponed supplementary parenteral nutrition on the risk of postoperative nosocomial infections following major emergency abdominal surgery. This is clinically relevant as nosocomial infections can significantly impact patient recovery and healthcare costs, and optimizing nutritional support timing may reduce these risks.

The clinical trial involves participants who have undergone **major emergency abdominal surgery**. The study population includes both male and female subjects aged 18 and above. Participants are required to have undergone a primary midline laparotomy or laparoscopy in an acute or sub-acute setting. The trial does not involve a vulnerable population. Participants must have an NRS-2002 score of less than 7 and no contraindications for oral or enteral intake post-surgery. Additionally, they should have an intake of less than 50% of the recommended caloric target on the second postoperative day and must be able to provide informed consent. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the impact of early versus postponed supplementary **parenteral nutrition** on postoperative nosocomial infections following major emergency abdominal surgery. This study is a randomized, controlled, multicenter trial, ensuring robust and unbiased results. The trial is expected to commence recruitment on February 1, 2024, and conclude by July 1, 2025, with an estimated duration of 18 months. Participants will be randomly assigned to either the early or postponed nutrition group, with both groups receiving the intervention in the form of an emulsion for infusion, specifically SmofKabiven or SmofKabiven Perifer.

Study visits are structured to include an initial screening visit, where eligibility criteria such as age (18 or above), surgical history, and nutritional status are assessed. Participants must have undergone a primary midline laparotomy or laparoscopy in an acute or sub-acute setting and demonstrate an intake of less than 50% of the recommended caloric target on the second postoperative day. Follow-up visits will be conducted to monitor the rate of infectious complications, length of hospital stay, and mortality rates at 30 and 90 days post-surgery. The end-of-study visit will evaluate the overall outcomes and any adverse events experienced by the participants.

The expected length of participant involvement is up to 1000 days, with a maximum daily dose of 2463 ml of the emulsion for infusion. Conditions that may lead to early termination from the study include the inability to provide informed consent, contraindications for oral or enteral intake after surgery, or any significant adverse events that compromise participant safety. The primary endpoint is a reduction in the rate of infectious complications during admission, while secondary endpoints include stratified complication rates, readmission rates, and energy and protein intake during admission. This trial aims to provide valuable insights into the optimal timing of supplementary parenteral nutrition in the postoperative care of patients undergoing major emergency abdominal surgery.

The clinical trial involves the administration of two experimental medications: **SmofKabiven** and **SmofKabiven Perifer**. Both medications are formulated as emulsions for infusion and are produced by Fresenius Kabi AB. The primary active substances in these formulations include a combination of amino acids such as **valine**, **alanine**, **arginine**, **histidine**, **isoleucine**, **leucine**, **methionine**, **phenylalanine**, **proline**, **serine**, **taurine**, **threonine**, **tyrosine**, and **glycine**. Additionally, the formulations contain refined **olive oil**, refined **soya-bean oil**, **medium chain triglycerides**, **tryptophan**, **potassium chloride**, **calcium chloride dihydrate**, **glucose monohydrate**, **magnesium sulfate heptahydrate**, **sodium acetate trihydrate**, **sodium glycerophosphate**, **lysine acetate**, **zinc sulphate heptahydrate**, and **fish oil rich in omega-3-acids**. The emulsions are administered via infusion, with a maximum daily dose of 2463 ml and a maximum treatment period of 1000 days.

**SmofKabiven** is an emulsion for infusion designed to provide parenteral nutrition. It contains a balanced mixture of amino acids, lipids, and electrolytes, which are essential for patients undergoing major emergency abdominal surgery. The administration route is through infusion, ensuring that the nutrients are delivered directly into the bloodstream. The dosing schedule is determined based on the patient's nutritional requirements, with careful monitoring to ensure compliance and adjust the dosage as needed.

**SmofKabiven Perifer** is a similar formulation to SmofKabiven, also provided as an emulsion for infusion. It is intended for peripheral administration, offering a less invasive option for patients who may not require central venous access. The composition of SmofKabiven Perifer mirrors that of SmofKabiven, ensuring that patients receive the necessary nutrients to support recovery and reduce the risk of postoperative nosocomial infections. The dosing and administration are tailored to the patient's condition, with regular assessments to ensure optimal nutritional support.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is on evaluating the effects of early versus postponed supplementary parenteral nutrition using the experimental medications. Participant compliance is monitored through regular follow-ups and assessments to ensure adherence to the dosing regimen and to evaluate the clinical outcomes effectively.

The efficacy of the clinical trial titled "Early Versus Postponed Supplementary Parenteral Nutrition After Major Emergency Abdominal Surgery: A Randomized, Controlled, Multicenter Study (the EATERS trial)" will be assessed using both primary and secondary endpoints. The primary endpoint is a reduction in the rate of infectious complications during admission. Secondary endpoints include the rate of complications during admission stratified by type and severity, length of stay, 30-day mortality, 90-day mortality, readmission rate and cause within 90 days, and energy and protein intake stratified by route, day, and amount during admission.

The trial aims to compare the effect of early and postponed supplementary parenteral nutrition on the risk of postoperative nosocomial infections following major emergency abdominal surgery. The study will utilize the product "SmofKabiven" and "SmofKabiven Perifer," both administered as an emulsion for infusion. The trial is designed to be low intervention and is categorized under trial phase 6. The estimated recruitment start date is February 1, 2024, with an estimated end date of July 1, 2025. The results of the trial will be summarized and made public within 12 months of its conclusion.