Parecoxib sequential with imrecoxib for occurrence and remission of severe acute pancreatitis: a multicentre, double-blind, randomised, placebo-controlled trial

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.

Keywords: ACUTE PANCREATITIS; CLINICAL TRIALS; CYCLOOXYGENASE-2.

Figure 1. Flow chart of enrolment. COPD, chronic obstructive pulmonary disease; COX-2-Is, cyclooxygenase-2 inhibitors; ICU, intensive care unit; ITT, intention-to-treat.

Figure 2. Duration of OF (A) and persistent OF (B) in the intention-to-treat population and persistent OF duration in patients without OF at enrolment (C) and with OF at enrolment (D). COX-2-Is, cyclooxygenase-2 inhibitors; OF, organ failure.

Figure 3. The changes in circulating inflammatory mediators and Systemic Inflammatory Response Syndrome (SIRS) Scores in two groups. CCL2, chemokine (C-C motif) ligand 2; COX-2-Is, cyclooxygenase-2 inhibitors; CRP, C reactive protein; CXCL16, chemokine (C-X-C motif) ligand 16; IL, interleukin.