Abstract
BACKGROUND: Post cholecystectomy pain is a common clinical problem. Investigation and management of patients with recurrent episodes of biliary pain and normal imaging is challenging. Low phospholipid associated cholelithiasis (LPAC) is a recently described syndrome that often presents with difficult to manage episodes of post cholecystectomy pain. Ursodeoxycholic acid (UDCA) treatment of LPAC is supported by animal studies and case series but has not been assessed in a randomised trial. METHODS: This protocol presents the design and rationale for an investigator-initiated, prospective, randomised, placebo-controlled, double-blind, Phase 3 crossover trial: Ursodeoxycholic acid in LPAC treating Recurrent Abdominal Pain (ULTRA Pain). The study population consists of 24 patients with difficult to manage post cholecystectomy pain diagnosed with LPAC with no or minimal changes on liver ultrasound imaging. Participants will be recruited through the gastroenterology clinic at Royal Melbourne Hospital and randomly assigned to receive UDCA 10 mg/kg daily for 1 year followed by a matched placebo, or vice versa, separated by an effective 6-week washout period. The primary endpoint is the number of patient reported episodes of biliary pain. Secondary outcomes include the number of episodes of biliary pain with associated transiently elevated liver function tests (LFTs), and episodes of biliary pain in those with the diagnosis of LPAC confirmed by ultrasound, the Recurrent Abdominal Pain Intensity and Disability (RAPID) score, and the score of several questionnaires measuring quality of life. An independent monitor has been appointed to oversee safety of participants. An intention-to-treat analysis will be performed in accordance with CONSORT guidelines. Regression methods appropriate to the type of primary or secondary outcome, such as linear regression for continuous outcome or Poisson or negative binomial regression if found to be skewed, or binary logistic regression for binary outcomes will be employed. Alpha or level of statistical significance will be set to p <0.05 and 95% confidence intervals will be reported throughout. DISCUSSION: This trial will provide level 1 evidence on the efficacy of UDCA in treating LPAC presenting with post cholecystectomy pain. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000450819).