Prevention of Severe Acute Pancreatitis With Cyclooxygenase-2 Inhibitors: A Randomized Controlled Clinical Trial

OBJECTIVES: Severe acute pancreatitis (SAP) is still a big challenge. Accumulated data showed that overexpression of cyclooxygenase-2 (COX-2) in acute pancreatitis and experimental pancreatitis could be attenuated with COX-2 inhibitors. This study was aimed to evaluate whether the occurrence of SAP could be prevented by selective COX-2 inhibitors. METHODS: A total of 190 patients with predicted SAP were randomized into convention group or convention plus COX-2 inhibitors (C+COX-2-Is) group. Besides conventional treatment to all patients in 2 groups, parecoxib (40 mg/d intravenous injection for 3 days) and celecoxib (200 mg oral or tube feeding twice daily for 7 days) were sequentially administrated to the patients in the C+COX-2-Is group. The primary outcome was predefined as the occurrence of SAP. The serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) for all of the patients were measured. RESULTS: The occurrence of SAP in the C+COX-2-Is group was decreased 47.08% compared with the convention group, 21.05% (20/95) vs 39.78% (37/93), P = 0.005. A reduction of late local complications was also shown in the C+COX-2-Is group, 18.95% (18/93) vs 34.41% (32/95), P = 0.016. The serum levels of IL-6 and TNF-α were significantly lower in the C+COX-2-Is group than those in the convention group, P < 0.05. Parecoxib relieved abdominal pain more rapidly and decreased the consumption of meperidine. An incremental reduction of cost for 1% decrease of SAP occurrence was RMB475. DISCUSSION: Sequential administration of parecoxib and celecoxib in patients with predicted SAP obtained about half-reduction of SAP occurrence through decreasing serum levels of TNF-α and IL-6. This regimen presented good cost-effectiveness.