Laparoscopic Cholecystectomy Versus Observation/Conservative Management for Preventing Recurrent Symptoms and Complications in Adults with Uncomplicated Symptomatic Gallstones (C-GALL): A Pragmatic, Multicentre Randomised Controlled Trial

Abstract

Background: In the adult population, gallstones have a global prevalence of 10-15%, although around 80% remain asymptomatic. Cholecystectomy remains the default treatment option for symptomatic gallstones. We assessed the clinical and cost-effectiveness of observation/conservative management compared with cholecystectomy for preventing symptoms and complications in adults with uncomplicated symptomatic gallstones.

Methods: A parallel group, pragmatic randomised, superiority trial in 20 UK centres. All adults with uncomplicated symptomatic gallstone disease referred to secondary care were considered for inclusion and randomly assigned (1:1) to receive observation/conservative management or cholecystectomy. The primary outcome was quality of life measured by area under the curve (AUC) over 18 months using the short form 36 (SF-36) bodily pain domain. NHS costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio were calculated.

Findings: Between August 2016-November 2019, 434 participants were randomised: 217 in each group. By 18 months, 54 (24·9%) in the observation/conservative management arm and 146 (67·3%) in the cholecystectomy arm had received surgery. The mean SF-36 norm-based bodily pain score was 49·4 (SD 11·7) in the observation/conservative management arm and 50·4 (SD 11·6) in the cholecystectomy arm. The SF-36 bodily pain AUC up to 18 months showed no difference (mean difference -0·0, 95% CI -1·7 to 1·7; p=1·00). Observation/conservative management was less costly (mean difference -£1,033 95% Credible Interval (CrI) -£1,413 to -£632) and no evidence of QALY difference was observed (mean difference -0.019, 95% CrI: -0.06 to 0.02).

Interpretation: In the short term (up to 18 months), observation/conservative management, as an alternative strategy to surgery, may be effective and cost-effective for uncomplicated symptomatic gallstones. As costs, complications and benefits will continue to be incurred in both groups beyond 18 months, future research should focus on longer-term follow-up to establish effectiveness and lifetime cost-effectiveness and identify the cohort of patients that should be routinely offered surgery.

Trial Registration: This trial is registered with the ISRCTN registry, number ISRCTN55215960.

Funding: National Institute for Health Research Health Technology Assessment Programme (Project 14/192/71).

Declaration of Interests: KG reports being a member of the NIHR HTA CET Committee member since 2020; JB reports grants from NIHR Bristol Biomedical Research Centre and being a member of the NIHR Clinical Trials Unit Standing Advisory Committee 2015 – 2019; SC is a co-investigator on unrelated grants from NIHR (HTA and EME programmes: NIHR129819, 15/130/95, 15/130/20) for which her institution has received payment; BC reports a Leadership or fiduciary role in the Association of Clinical Biochemistry and Laboratory medicine as president 2021 – 2023 and Royal College of Pathologists as Trustee and Scottish Chair; CR reports grants from UK National Institute for Health Research, during the conduct of the study and Member of the NIHR HTA General funding committee from 2017 to present. All others have nothing to declare.

Ethics Approval: The trial was approved by the North of Scotland Research Ethics Committee on May 23rd, 2016 (reference number 16/NS/005) and the protocol was published in 2021.

Keywords: Randomised controlled trial, gallstones, cholecystectomy, cholelithiasis, conservative treatment