Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after Roux-en-Y gastric bypass and sleeve gastrectomy

The number of bariatric interventions for morbid obesity is increasing rapidly. Rapid weight loss is a major risk factor for gallstone development. Approximately eleven percent of patients who underwent Roux-en-Y gastric bypass develop symptomatic gallstone disease. After sleeve gastrectomy similar incidences of symptomatic gallstone disease are reported. 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 centres do not prescribe UDCA.


We will conduct a randomized, placebo-controlled, double-blind multicentre trial. The study population consists of consecutive patients undergoing Roux-en-Y gastric bypass or sleeve gastrectomy in the MC Slotervaart, OLVG West and MC Zuiderzee Lelystad. Patients will receive a preoperative ultrasound, randomisation will be stratified for patients already having gallstones and type of surgery. The intervention group will receive UDCA 900mg 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 and side-effects of UDCA. Cost-effectiveness, cost-utility and budget impact analyses will be performed with costs per patient with poor outcome, costs per quality adjusted life year, respectively total reimbursement as primary outcomes.

Rapid weight loss is a major risk factor for gallstone development. Approximately eleven percent of patients who underwent Roux-en-Y gastric bypass develop symptomatic gallstone disease. After sleeve gastrectomy similar incidences of symptomatic gallstone disease are reported. 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 centres do not prescribe UDCA.

This study is designed to provide evidence regarding the prophylactic use of UDCA in preventing symptomatic gallstone disease after bariatric surgery.

Regular care includes follow-up appointments at 2 and 6 weeks, 4, 6, 12 and 24 months. The study ends after 24 months of follow-up.

Ursodeoxycholic acid is an artificial bile acid that reduces the ratio of cholesterol to bile salts plus phospholipids in bile, causing desaturation of cholesterol saturated bile. In this study it is prescribed as tablets of 450mg, 2 tablets once daily or 1 tablet twice daily. The placebo will be similar in look but without active ingredients.



Prior to surgery, an ultrasound of the gallbladder is performed in each patient. Randomization is stratified for the presence of gallstones and type of surgery.