Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, the Netherlands.
Trials. 2020 Jul 23;21(1):676. doi: 10.1186/s13063-020-04605-7.
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.
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.
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.
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.
The Netherlands Trial Register NL5954 . Registered on 21 November 2016.
大约有 8-15%接受减重手术的患者在手术后 24 个月内会出现有症状的胆结石疾病。熊去氧胆酸（UDCA）似乎可以有效预防减重手术后通过超声检测到的胆结石形成。UPGRADE 试验的目的是提供 UDCA 预防术后有症状的胆结石疾病的预防性使用的证据。
UPGRADE 试验是一项针对接受 Roux-en-Y 胃旁路术（RYGB）或袖状胃切除术（SG）的病态肥胖患者的随机、安慰剂对照、双盲多中心试验。患者被随机分配接受 UDCA 900mg 每日治疗 6 个月或安慰剂治疗。本文详细介绍了该试验的统计分析计划（SAP），并在获得结果数据之前提交。
该试验的主要终点是减重手术后 24 个月内出现有症状的胆结石疾病，定义为因有症状的胆结石疾病入院或就诊。次要结局包括在基线时胆囊结石阴性组的 24 个月时超声检查显示胆囊结石/沉积物、24 个月时超声检查显示胆囊结石/沉积物、胆囊切除术数量、UDCA 的副作用、治疗依从性、生活质量、成本和收益。分析将根据本预先指定的 SAP 进行。主要分析将作为标准的 ITT 分析，使用卡方检验进行。
UPGRADE 试验将显示预防性使用 UDCA 是否可以降低减重手术后有症状的胆结石疾病的发生率。在分析时，如果出现与 SAP 未预料到的偏差，将进行说明和讨论。
荷兰试验注册 NL5954。于 2016 年 11 月 21 日注册。
