Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery: study protocol for a randomized controlled trial (UPGRADE trial).

BACKGROUND: The number of bariatric interventions for morbid obesity is increasing worldwide. Rapid weight loss is a major risk factor for gallstone development. Approximately 11 % of patients who underwent Roux-en-Y gastric bypass develop symptomatic gallstone disease. Gallstone disease can lead to severe complications and often requires hospitalization and surgery. Ursodeoxycholic acid (UDCA) prevents the formation of gallstones after bariatric surgery. However, randomized controlled trials with symptomatic gallstone disease as primary endpoint have not been conducted. Currently, major guidelines make no definite statement about postoperative UDCA prophylaxis and most bariatric centers do not prescribe UDCA. METHODS: A randomized, placebo-controlled, double-blind multicenter trial will be performed for which 980 patients will be included. The study population consists of consecutive patients scheduled to undergo Roux-en-Y gastric bypass or sleeve gastrectomy in three bariatric centers in the Netherlands. Patients will undergo a preoperative ultrasound and randomization will be stratified for pre-existing gallstones and for type of surgery. The intervention group will receive UDCA 900 mg once daily for six months. The placebo group will receive similar-looking placebo tablets. The primary endpoint is symptomatic gallstone disease after 24 months, defined as admission or hospital visit for symptomatic gallstone disease. Secondary endpoints consist of the development of gallstones on ultrasound at 24 months, number of cholecystectomies, side-effects of UDCA and quality of life. Furthermore, cost-effectiveness, cost-utility and budget impact analyses will be performed. DISCUSSION: The UPGRADE trial will answer the question whether UDCA reduces the incidence of symptomatic gallstone disease after Roux-en-Y gastric bypass or sleeve gastrectomy. Furthermore it will determine if treatment with UDCA is cost-effective. TRIAL REGISTRATION: Netherlands Trial Register (trialregister.nl) 6135 . Date registered: 21-Nov-2016.

Estimation of the cost savings resulting from the use of ursodiol for the prevention of gallstones in obese patients undergoing rapid weight reduction.

BACKGROUND: Morbidly obese patients enrolled in a rapid weight reduction program are at a high risk of developing gallstones. Two multicenter, placebo-controlled, randomized, double-blind trials have demonstrated that the prophylactic use of ursodiol in males and females 18 to 70 years of age is effective for the prevention of gallstone formation in this patient population. This study examines the cost consequences associated with the prophylactic use of ursodiol. METHODS: A medical decision analysis model for the prophylactic administration of ursodiol in morbidly obese patients undergoing rapid weight reduction by either gastric bypass surgery or very-low-calorie-diet, was developed through the use of data from two clinical trials and review of the related literature. The expert opinion of clinicians from the fields of internal medicine, gastroenterology and surgery were solicited. Financial data for the charges associated with cholecystectomies, physician fees and ursodiol were obtained from current financial databases. RESULTS: The model demonstrates that the prophylactic administration of ursodiol, in morbidly obese patients undergoing rapid weight reduction, results in cost savings. Sensitivity analysis was performed to illustrate that the cost savings achieved by the prophylactic use of ursodiol were valid over a realistic range of charges and assumptions. CONCLUSION: The decision model may allow health care decision makers to apply their own data to the model to determine the cost savings obtainable through the prophylactic use of ursodiol in patients undergoing rapid weight reduction.