Parecoxib sequential with imrecoxib for occurrence and remission of severe acute pancreatitis: a multicentre, double-blind, randomised, placebo-controlled trial
Luming Huang et al.
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.
WHAT IS ALREADY KNOWN ON THIS TOPIC
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There is no effective drug treatment for organ failure (OF) caused by severe acute pancreatitis (SAP).
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Overexpression of cyclooxygenase-2 (COX-2) has been observed in rat models of acute pancreatitis and COX-2 inhibitors (COX-2-Is) have shown potential in improving respiratory and renal function.
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The randomised controlled trial in our single centre showed that COX-2-Is may decrease SAP occurrence in the patients who have been sick for 2 days.
WHAT THIS STUDY ADDS
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COX-2-Is not only effectively reduced the occurrence of SAP but also significantly shortened the duration of OF through alleviating systemic inflammation.
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Early anti-inflammation with COX-2-Is is of importance, but delayed patients can also benefit from this treatment.
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The clinical outcomes, including OF, local complications and 30-day mortality, were significantly improved by COX-2-Is, and the duration of hospital stay and the cost during hospitalisation were also reduced significantly.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
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This multicentre, double-blind, randomised, placebo-controlled trial provides important insights for advancing translational medicine research on the treatment of SAP with COX-2-Is.
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The easy regime of COX-2-Is for SAP treatment has the potential to change clinical practice.
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The clinical outcomes of SAP would be improved with early and extensive use of COX-2-Is.
