Robotic versus open pancreatoduodenectomy (SPAIN Trial): protocol for a multicenter randomized controlled trial assessing safety, efficacy and cost-effectiveness

Minimally invasive pancreatoduodenectomy (PD), particularly through a robotic approach (RPD), is gaining increasing worldwide acceptance. However, high-quality evidence remains limited and very few randomized controlled trials have directly compared RPD with open PD (OPD). The SPAIN Trial (Spanish Pancreatoduodenectomy: Open vs. Robotic Approach) is designed to generate national evidence on the safety, efficacy, and economic value of RPD compared with the open technique. This is a national, multicentre, randomized, prospective, non-inferiority trial comparing RPD and OPD in high-volume Spanish centres with established robotic pancreatic programs. Adult patients indicated for elective PD due to benign or malignant disease of the pancreatic head, distal bile duct, duodenum, or ampulla of Vater will be randomized in a 2:1 ratio (2RPD:1OPD). The primary endpoint is overall postoperative morbidity within 90 days, assessed by the Comprehensive Complication Index (CCI). Secondary endpoints include intraoperative outcomes (operative time, blood loss, conversion rate), ISGPS-defined pancreatic complications, oncological outcomes (R0 resection, lymph node yield, time to adjuvant therapy), length of stay, readmission rates, and patient-reported quality of life using EQ-5D-5 L, EORTC QLQ-C30, and PAN-26 questionnaires. Cost-effectiveness will be assessed using Quality-Adjusted Life Years (QALYs) and Incremental Cost-Effectiveness Ratios (ICERs) from a healthcare perspective.Trial registration: ClinicalTrials.gov Identifier NCT06981273.