A randomized controlled trial to compare a restrictive strategy to usual care for the effectiveness of cholecystectomy in patients with symptomatic gallstones (SECURE trial protocol)

Abstract

BackgroundFive to 22 % of the adult Western population has gallstones. Among them, 13 to 22 % become symptomatic during their lifetime. Cholecystectomy is the preferred treatment for symptomatic cholecystolithiasis. Remarkably, cholecystectomy provides symptom relief in only 60-70 % of patients. The objective of this trial is to compare the effectiveness of usual (operative) care with a restrictive strategy using a standardized work-up with stepwise selection for cholecystectomy in patients with gallstones and abdominal complaints.Design and methodsThe SECURE-trial is designed as a multicenter, randomized, parallel-arm, non-inferiority trial in patients with abdominal symptoms and ultrasound proven gallstones or sludge. If patients meet the inclusion criteria they will be randomized to either usual care or the restrictive strategy.Patients in the usual care group will be treated according to the physician’s knowledge and preference. Patients in the restrictive care group will be treated with interval evaluation and stepwise selection for laparoscopic cholecystectomy. In this stepwise selection, patients strictly meeting the preselected criteria for symptomatic cholecystolithiasis will be offered a cholecystectomy. Patients not meeting these criteria will be assessed for other diagnoses and re-evaluated at 3-monthly intervals. Follow-up consists of web-based questionnaires at 3, 6, 9 and 12 months.The main end point of this trial is defined as the proportion of patients being pain-free at 12 months follow-up. Pain will be assessed with the Izbicki Pain Score and Gallstone Symptom Score.Secondary endpoints will be the proportion of patients with complications due to gallstones or cholecystectomy, the association between the patients’ symptoms and treatment and work performance, and ultimately, cost-effectiveness.DiscussionThe SECURE trial is the first randomized controlled trial examining the effectiveness of usual care versus restrictive care in patients with symptomatic gallstones. The outcome of this trial will inform clinicians whether a more restrictive strategy can minimize persistent pain in post-operative patients at least as good as usual care does, but at a lower cholecystectomy rate. (The Netherlands National Trial Register NTR4022, 17th December 2012)Trial registrationThe Netherlands National Trial Register NTR4022http://www.zonmw.nl/nl/projecten/project-detail/scrutinizing-inefficient-use-of-cholecystectomy-a-randomized-trial-concerning-variation-in-practi/samenvatting/

Statistical analysis plan of a randomized controlled trial to compare a restrictive strategy to usual care for the effectiveness of cholecystectomy (SECURE trial)

“…On 26 April 2017, all patients will be included and the completed follow-up is expected in May 2018. The power analysis and other study procedures are further detailed in the previously published trial protocol [ 3 ].…”

“…Informed consent is obtained from the patients according to the SECURE trial protocol [ 3 ]. Patients who withdrew their consent after randomisation will be excluded from further follow-up and analysis.…”

“…The SECURE trial is designed to examine the effectiveness of usual care versus restrictive strategy in patients with symptomatic gallstones. The trial protocol was previously published [ 3 ] and present article is the proposed statistical analysis plan (SAP). The SAP was written by the investigators before any of the outcomes were available.…”

Regional variations in cholecystectomy rates in Sweden: impact on complications of gallstone disease

“…When treating patients with gallstones, it is essential to distinguish between patients who have had a complication and those who do not. Due to lack of randomized controlled trials on the natural history of gallstone disease, the available evidence on this topic is based on epidemiological studies [de Reuver et al 2016] and clinical experience. According to the NIH consensus guidelines, it is generally accepted that asymptomatic patients do not require any surgical treatment [NIH consensus statement 1992;Gollan JL et al 1993].…”

Relationship between clinical and histopathological features of patients undergoing cholecystectomy

“…Cholelithiasis is present in 5% to 22% of Western populations, and 13-22% of them are symptomatic throughout their lifetime. Complicated cholelithiasis has a 5% risk of causing lifelong choledocholithiasis, acute cholecystitis, acute pancreatitis, or cholangitis [1,2]. Acute cholecystitis occurs in 10-20% of those with untreated cholelithiasis [3,4].…”