Description

The LowCaLi study is a multicentre, open-label, randomized controlled trial.

Hypothesis

• A 7-day preoperative LCD reduces postoperative complications.
• LCD reduces intraoperative bleeding and postoperative complication rate.
• LCD reduces liver volume, facilitates access, and shortens operating time.
• LCD decreases hepatic glycogen and steatosis.
• LCD improves coagulation.
• LCD modifies plasma lipid and fatty acid composition.

Primary Objective To investigate whether a 7-day preoperative LCD reduces postoperative complications as measured by the Comprehensive Complication Index (CCI).

Secondary Objectives

• To assess the effect of LCD on intraoperative blood loss and transfusion requirements.
• To evaluate parenchymal dissection time and total surgical duration.
• To measure hospital length of stay.
• To determine R0 resection rate (tumour-free margins).
• To analyse systemic inflammatory response.
• To evaluate compliance with the intervention.
• To assess health-related quality of life (QLQ-C30).

Sample Size Calculation Barth et al. (2019) demonstrated a reduction in bleeding from 300 ml to 200 ml with LCD, requiring 32 patients for 80% power at α=0.05. For CCI reduction (21→13, SD=20), 98 patients per arm are required. To account for attrition, 200 patients (100 per group) will be recruited.

Study Procedures

• Screening and randomization at preoperative visit
• LCD intervention: 7 days prior to surgery
• Follow-up phone calls during the intervention period
• Structured intraoperative assessment by surgeon
• Postoperative follow-up including complications, pathology, and length of stay
• Patient-reported outcomes collected preoperatively and at 30 days postoperatively

Workflow Eligible patients will be identified during the mandatory pre-surgery outpatient visit. Written and oral study information will be provided, and informed consent obtained. Patients will then be randomized (1:1) using a web-based module in the eCRF (RedCap).

Randomization will be stratified by surgical approach (open vs. minimally invasive). The intervention group will follow a 7-day LCD (1000 kcal/day), using a standardized commercial product such as for example Modifast). The control group will receive standard preoperative care, including carbohydrate preloading, without diet restriction.

Study nurses will provide dietary instructions and monitor compliance through scheduled phone calls. Following surgery, the operating surgeon will complete a structured form documenting liver mobility, parenchymal texture, and intraoperative blood loss. Patient-reported quality of life will be assessed preoperatively and 30 days postoperatively.

Withdrawal of Individual Subjects Participation is voluntary. Patients may withdraw at any time without consequences for clinical care.

Follow-up of Subjects Withdrawn from Treatment Data collected up to the time of withdrawal will be included if the patient consents.

Statistical Analysis Primary analysis: comparison of CCI between groups using t-test or Mann-Whitney U test. Secondary analyses: regression models for continuous outcomes, chi-square/Fisher's exact tests for categorical data, and Kaplan-Meier analysis for time-to-event outcomes. Both intention-to-treat and per-protocol analyses will be performed.

ETHICAL CONSIDERATIONS Regulation Statement: The study will be conducted in accordance with the Declaration of Helsinki, ICH-GCP, and national legislation. Recruitment and Consent: To avoid bias, brief study information will be given to all eligible patients before randomization. Full dietary details will only be disclosed to participants allocated to the intervention group. Written informed consent is required prior to enrolment. The intervention group will be recieve LCD för 7 days or be compensated for the extra cost due to LCD diet, in arrears.

Compensation for Injury Patients are covered by national patient insurance schemes. No monetary compensation will be provided to participants.

ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION Handling and storage of data and documents The sponsor and the trial management team will oversee the conduct of the trial according to Good Clinical Practice (GCP). The local investigators will be responsible for conduct at their respective sites.

Data will be handled confidentially. Each patient will receive an anonymous identification code. To trace data, a subject identification code list will be used. Each participating site will keep the key to this code secure. The handling of data will comply with the EU General Data Protection Regulation (GDPR).

Data will be kept for a minimum of ten years according to current regulations. Data will be entered into the eCRF using the electronic online database RedCap. Data to be collected are derived from the protocol.

The CRF and instructions for completing it will be provided by the Clinical Trial Centre/Västra Götaland, Sweden.

Handling and Storage of Data and Documents

• Data will be recorded in the eCRF (RedCap).
• Source data will be extracted from medical records.
• Records will be retained for at least 10 years after study completion.