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

Am J Gastroenterol. 2020 Mar;115(3):473-480. doi: 10.14309/ajg.0000000000000529.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Celecoxib / therapeutic use*
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Intravenous
  • Isoxazoles / therapeutic use*
  • Male
  • Middle Aged
  • Pancreatitis / diagnosis
  • Pancreatitis / prevention & control*
  • Prospective Studies
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Substances

  • Cyclooxygenase 2 Inhibitors
  • Isoxazoles
  • parecoxib
  • Celecoxib

Associated data

  • ChiCTR/ChiCTR-TRC-14005059