A randomised controlled trial to establish the clinical and cost effectiveness of expectant management versus pre-operative imaging with MRCP in patients with symptomatic gallstones undergoing laparoscopic cholecystectomy at low or moderate risk of common bile duct stones: The Sunflower Study

Design: Multi-centre pragmatic randomised controlled trial (RCT) with an internal pilot phase (Phase 1) and a Quintet Recruitment Intervention (QRI). Phase 1 will determine the feasibility of recruitment, adherence to the allocation and data collection processes. Progression to Phase 2 will depend on meeting the progression criteria set for Phase 1. The full RCT will evaluate the effectiveness and cost effectiveness of preoperative magnetic resonance pancreaticogram (MRCP) for the treatment of symptomatic gallstone disease. Participants will be randomised in a 1:2 ratio to MRCP:no MRCP (expectant management). Randomisation will be via a secure website to ensure allocation concealment. Setting: Secondary and tertiary care. The study will recruit from 50 centres. Target population: Adults referred for surgery with symptomatic gallstone disease at low or moderate risk of common bile duct (CBD) stones (based on abdominal ultrasound and liver function tests). Exclusion criteria: High risk of CBD stones, empyema/perforated gallbladder/severe pancreatitis, contraindications to MRCP, haemolytic disease, pregnancy, unable to consent and/or be followed up, ASA IV. Health technologies being assessed: Preoperative MRCP or no MRCP. Intra-operative cholangiogram will be prohibited unless needed to clarify anatomy. Measurement of costs and outcomes: Primary outcome for the full trial will be a composite of any hospital admission for treatment of a complication of gallstones, whether in the CBD or gallbladder within 18 months after randomisation. Admissions will be identified from hospital episode statistics (HES), adjudicated by independent judges blind to allocation in the pilot phase. Secondary outcomes will include: EQ-5D-5L and symptoms of gallstones at baseline (SF-12), on admission for laparoscopic cholecystectomy (LC) and at 3, 6, 12 and 18 months after randomisation (20% sample), items in the LC core outcome set, time from randomisation to surgery, NHS resource use. Costs and cost per QALY will be estimated. Events after discharge will be obtained through linkage with HES. Sample size: We aim to recruit 13,680 participants in total (4,560 MRCP, 9,120 no MRCP). This will provide 90% power to detect a non-inferiority margin >=1.5% in the primary outcome assuming an event rate of 7% at 2.5% one-tailed statistical significance. We expect to recruit about 2140 participants in Phase 1 and the remainder by the end of Phase 2. Criteria for progression from Phase 1 to 2: At least 30 centres open, > 1750 participants randomised, at least 90% of randomised participants adhere to the allocated pathway, evidence that the primary outcome can be reliably identified from routine data. Project Timetable: 72 months: 6m set-up; 48m recruitment (Phase 1: 16m; Phase 2: 32m); minimum 12m follow-up on all participants (median follow-up 18m); 6m analysis and report. Expertise in team: The team is multidisciplinary and includes patients, surgeons, radiologists, health economist, trialists/methodologists, a UKCRC-registered clinical trials unit, an MRC methodology Hub and a Royal College of Surgeons Trials centre.