Abstract
BACKGROUND: There is no effective drug treatment for the organ failure (OF) caused by severe acute pancreatitis (SAP). OBJECTIVE: We aimed to evaluate the efficacy of cyclooxygenase-2 inhibitors (COX-2-Is) on the treatment of SAP and its safety. DESIGN: In this multicentre, double-blind, randomised, placebo-controlled, investigator-initiated trial, 348 patients with acute pancreatitis aged 18-75 years, <1 week from onset of illness to admission, and Acute Physiology and Chronic Health Evaluation II Score ≥7 or modified Marshall Score ≥2, were randomly assigned (1:1) to the COX-2-Is group (parecoxib sequential with imrecoxib) or the placebo group. SAP occurrence, duration of OF, local complications, clinical outcomes and serum inflammatory mediators were measured. RESULTS: Compared with the placebo group, SAP occurrence was reduced by 20.7% (77.6% vs 61.5%, p=0.001) and the persistent OF duration in SAP was shortened by 2 days (p<0.001) after COX-2-Is treatment. For patients enrolled within or after 48 hours from symptom onset, SAP occurrence was reduced by 23.8% (p=0.001) and 8.5% (p=0.202), and the persistent OF duration in SAP was shortened by 3 days (p=0.001) and 2 days (p=0.010) after COX-2-Is treatment, respectively. The occurrence of local complications in the COX-2-Is group was significantly lower than those in the placebo group, 33.7% vs 49.1%, p=0.004. The serum levels of inflammatory mediators and 30-day mortality (from 8.6% to 3.4%) were significantly reduced after COX-2-Is treatment, p<0.05. The incidence of adverse events was similar between the two treatment groups. CONCLUSION: Parecoxib sequential with imrecoxib was effective and well tolerated in reducing the occurrence and duration of SAP and local complications through suppression of systemic inflammatory response, leading to decreased morbidity.