One-step laparoscopic cholecystectomy with common bile duct exploration and stone extraction versus two-step endoscopic retrograde cholangiography with stone extraction plus laparoscopic cholecystectomy for patients with common bile duct stones: a statistical analysis and central data monitoring plan for a pilot and feasibility randomised clinical trial

Background Endoscopic retrograde cholangiography (ERC) with stone extraction and papillotomy with subsequent laparoscopic cholecystectomy — the two-step approach — is the standard treatment of common bile duct stones in many countries. However, ERC is associated with a high risk of complications, and more than half of patients require multiple ERCs. Meta-analyses of randomised clinical trials find no major differences of the two-step approach in comparison with laparoscopic cholecystectomy with intraoperative laparoscopic stone clearance — the one-step approach. Currently, there are insufficient data to ascertain superiority. Methods The preGallstep trial is an investigator-initiated, multicentre randomised pilot and feasibility clinical trial with blinded outcome assessment. Eligible participants are patients with common bile duct stones (identified by magnetic resonance cholangio-pancreatography), age 18 years or above, and with the possibility to perform both interventions within a reasonable time. We intend to randomise 150 participants allocated 1:1. The experimental intervention is the one-step approach. This consists of laparoscopic common bile duct exploration plus laparoscopic cholecystectomy. The control intervention is the two-step approach which consists of ERC plus sphincterotomy (first step) and subsequent laparoscopic cholecystectomy (second step). The pilot outcome is the proportion of participants with at least one postoperative complication according to the Clavien-Dindo score grade II and above until 90 days after randomisation. This outcome will be used for a future sample size calculation of a larger pragmatic trial. A range of feasibility outcomes will be assessed to ascertain feasibility of the trial. Furthermore, a range of clinical outcomes will be assessed exploratorily. After completion of the feasibility trial, blinded data will be analysed by two independent statisticians blinded to the intervention, where ‘A’ and ‘B’ refers to the two groups. A third party will compare these reports and discrepancies will be discussed. The statistical report with the analyses chosen for the manuscript is being tracked using a version control system, and both statistical reports will be published as supplementary material. Based on the final statistical report, two blinded conclusions will be drawn by the steering group. Discussion We present a pre-defined statistical analysis plan and data monitoring scheme for the preGallstep pilot and feasibility trial, which, limits bias, p-hacking, and data-driven interpretations. Trial registration: ClinicalTrials.gov, NCT04801238. Registered on March 16, 2021 https://clinicaltrials.gov/ct2/show/NCT04801238