TY - JOUR
T1 - Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery: statistical analysis plan for a randomised controlled trial (UPGRADE trial)
AU - Haal, Sylke
AU - Guman, Maimoena S. S.
AU - de Brauw, L. Maurits
AU - van Veen, Ruben N.
AU - Schouten, Ruben
AU - Fockens, Paul
AU - Gerdes, Victor E. A.
AU - Dijkgraaf, Marcel G. W.
AU - Voermans, Rogier P.
PY - 2020/7/23
Y1 - 2020/7/23
N2 - BACKGROUND: Approximately 8-15% of patients undergoing bariatric surgery develop symptomatic gallstone disease within 24 months after surgery. Ursodeoxycholic acid (UDCA) seems to effectively prevent the formation of gallstones detectable by ultrasound after bariatric surgery. The aim of the UPGRADE trial is to provide evidence on the prophylactic use of UDCA in preventing symptomatic gallstone disease postoperatively. METHODS: The UPGRADE trial is designed as a randomised, placebo-controlled, double-blind multicentre trial in patients with morbid obesity undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Patients are randomly assigned to either UDCA 900 mg daily for 6 months or placebo treatment. This paper details the statistical analysis plan (SAP) of this trial and was submitted before outcome data were available. RESULTS: The primary endpoint of this trial is symptomatic gallstone disease within 24 months after bariatric surgery, defined as admission or hospital visit for symptomatic gallstone disease. Secondary outcomes consist of the development of gallstones/sludge on ultrasound at 24 months in the gallstone-negative group at baseline, presence of gallstones/sludge on ultrasound at 24 months, number of cholecystectomies, side effects of UDCA, therapy compliance, quality of life, costs and revenues. Analyses will be completed according to this pre-specified SAP. The main analysis will be performed as a standard ITT analysis using the chi-squared test. DISCUSSION: The UPGRADE trial will show if prophylactic use of UDCA reduces the incidence of symptomatic gallstone disease after bariatric surgery. Unforeseen deviations from the SAP at the time of analysis will be motivated and discussed. TRIAL REGISTRATION: The Netherlands Trial Register NL5954 . Registered on 21 November 2016.
AB - BACKGROUND: Approximately 8-15% of patients undergoing bariatric surgery develop symptomatic gallstone disease within 24 months after surgery. Ursodeoxycholic acid (UDCA) seems to effectively prevent the formation of gallstones detectable by ultrasound after bariatric surgery. The aim of the UPGRADE trial is to provide evidence on the prophylactic use of UDCA in preventing symptomatic gallstone disease postoperatively. METHODS: The UPGRADE trial is designed as a randomised, placebo-controlled, double-blind multicentre trial in patients with morbid obesity undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Patients are randomly assigned to either UDCA 900 mg daily for 6 months or placebo treatment. This paper details the statistical analysis plan (SAP) of this trial and was submitted before outcome data were available. RESULTS: The primary endpoint of this trial is symptomatic gallstone disease within 24 months after bariatric surgery, defined as admission or hospital visit for symptomatic gallstone disease. Secondary outcomes consist of the development of gallstones/sludge on ultrasound at 24 months in the gallstone-negative group at baseline, presence of gallstones/sludge on ultrasound at 24 months, number of cholecystectomies, side effects of UDCA, therapy compliance, quality of life, costs and revenues. Analyses will be completed according to this pre-specified SAP. The main analysis will be performed as a standard ITT analysis using the chi-squared test. DISCUSSION: The UPGRADE trial will show if prophylactic use of UDCA reduces the incidence of symptomatic gallstone disease after bariatric surgery. Unforeseen deviations from the SAP at the time of analysis will be motivated and discussed. TRIAL REGISTRATION: The Netherlands Trial Register NL5954 . Registered on 21 November 2016.
KW - Bariatric surgery
KW - Randomised controlled trial
KW - Statistical analysis plan
KW - Symptomatic gallstone disease
KW - Ursodeoxycholic acid
UR - http://www.scopus.com/inward/record.url?scp=85088539976&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13063-020-04605-7
DO - https://doi.org/10.1186/s13063-020-04605-7
M3 - Article
C2 - 32703246
SN - 1745-6215
VL - 21
SP - 676
JO - Trials
JF - Trials
IS - 1
M1 - 676
ER -