A randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of laparoscopic cholecystectomy compared with observation/conservative management for preventing recurrent symptoms and complications in adults with uncomplicated symptomatic gallstones (C-Gall)

Design: Parallel group, multi-centre patient randomised superiority trial with 24 month follow-up. Embedded qualitative research will identify any challenges during an internal pilot phase. Setting: Secondary care Participants: Adults with symptomatic uncomplicated gallstone disease referred to a secondary care setting. Exclusion criteria: Unable to consent, medically unfit for surgery, current pregnancy, previous open major upper abdominal surgery, gallstones in common bile duct or evidence of previous choledocholothiasis refers to gallstones in common bile duct on latest imaging or evidence of previous choledocholothiasis, a history of acute pancreatitis, evidence of obstructive jaundice, evidence of empyema of gallbladder with sepsis, suspicion of gallbladder cancer, perforated gallbladder refers to recent or old perforation detected on imaging, haemolytic disease. Health technologies being assessed: (i) Laparoscopic cholecystectomy: (ii) Observation/conservative management: Primary outcomes: patient outcome measure - QOL as measured by area under the curve (AUC) at up to 18 months post-randomisation using the SF-36 (AUC measures at 3, 9 12, and 18 months). Economic outcome measure - incremental cost per QALY. Secondary outcomes: Condition specific quality of life (CSQ)a,b; complications; need for further treatment; persistent symptoms; health care resource use; costs. The AUC at up to 24 months post-randomisation for the SF-36 bodily pain will be reported. Data collection: The patient reported outcomes (SF-36; CSQ) will be assessed by participant-completed questionnaires at baseline, 3, 9, 12 and 18 months and 6 monthly thereafter until the end of the trial. A case report form (CRF) at the time of surgery providing details of the operative procedures, complications and resource use in hospital. Costs of the initial intervention procedures will be estimated from resource use data recorded on the case report forms coupled with routine unit cost data. Costs associated with subsequent contacts with primary and secondary care (due to symptomatic gallstones) will be estimated at 3, 9, 12 and 18 months and 6 monthly thereafter, post randomisation, till end of trial and checked at source. QALYs will be estimated from patients’ responses to the SF-36. Sample size: To detect a 0.33 of a standard deviation difference in the area under the curve (AUC) of the SF-36, 90% power with alpha 5%, 194 participants per group (388 total) are required. Such a difference in generic health status is considered clinically relevant and in terms of treatment effect size, in the small to medium range as observed in other clinical studies. To allow for the anticipated approximately 10% of participants for whom outcome data is completely missing, and therefore the AUC cannot be calculated, it is proposed to randomise 430 participants. Project timetable: The projected start date is 1 April 2016: the study duration will be 72 months. Milestones are: Pre-funding-multicentre research ethics and central R&D approvals Month 2-First steering group meeting. Month 4–30- Centre recruitment; recruit local staff. Month 7–42- Recruit patients (staggering centre start up). Month 12- a) Qualitative interviews completed b) Stop/go assessment (patient recruitment). c) Core outcome set completed.Month 18- Stop/go assessment (centre recruitment) Month 66- Final patient follow-up Month 67-71- Data cleaning and analyses Month 72- Final report Recruitment rate: The trial centres conduct an average of 500 cholecystectomies/year. At least 10-20% (50-100) of the patients would be eligible. With a 36 month recruitment period (months 7-42 inclusive) based on a conservative throughput of 50 eligible patients/year in 20 centres with the assumption that 50% of eligible patients in the first month and 50% in Aug and Dec will be missed. We expect that 40% of the remaining eligible patients will be willing to be randomised. The first 20 patients recruited by Month 12, 111 patients by Month 18 and the remaining 319 patients by Month 42 (n=430)