A multicentre randomized non-inferiority trial comparing usual care to restrictive strategy for use of cholecystectomy in patients with gallstones and abdominal pain (SECURE trial)

Abstract

Background: Cholecystectomy is the preferred treatment for symptomatic, uncomplicated gallstones. Usual care in patients with abdominal pain and gallstones is associated with practice variation and persistent abdominal pain in 10-41% of post-cholecystectomy patients. We scrutinized (in)efficient use of cholecystectomy by determining non-inferiority of a restrictive strategy with stepwise selection compared to current usual care for patients with abdominal pain and gallstones. Material & Methods: We randomly assigned patients with ultrasound proven gallstones and abdominal symptoms from 24 Dutch hospitals, to a restrictive strategy with stepwise selection for cholecystectomy or usual care. The primary endpoint was the proportion of patients being pain-free at 12 months' follow-up. A 5% non-inferiority margin was chosen, based on estimated clinical relevant difference. Secondary endpoints included: cholecystectomy rate, proportion of patients with gallstone related and surgical complications, patients' satisfaction, health status and time to pain-free. Results: Between 2014-2018, 1067 patients were included. At 12 months’ follow-up 298 of 530 patients (56.2%, 95% CI, 52.0%-60.4%) were pain-free in the restrictive strategy, compared to 321 of 537 patients (59.8%, 95% CI, 55.6%-63.8%) in usual care. Non-inferiority was not demonstrated as the lower limit of 95% confidence interval of pain-free patients exceeds the 5% non-inferiority margin. (pnon-inferiority = 0.316). The restrictive strategy resulted in a significantly lower cholecystectomy rate than usual care (67.7% versus 75.4%, p=0.005). Other secondary outcomes were comparable between groups: median time to pain-free (7.87 months versus 7.29 months, p=0.130), patient satisfaction with treatment outcome at 12 months’ follow-up (p=0.976), and patients’ health status over time (p=0.820). Overall, patients with preoperative biliary colics were more often pain-free after cholecystectomy (65.5% versus 57.4%, p=0.048). Conclusion: The restrictive strategy is associated with less cholecystectomies. However, suboptimal pain reduction in patients with gallstones and abdominal pain is seen in both usual care and following a restrictive strategy for selection for cholecystectomy.