Parecoxib sequential with imrecoxib for occurrence and remission of severe acute pancreatitis: a multicentre, double-blind, randomised, placebo-controlled trial
Li Huang, Zhe Feng, Wenjuan Yang, Yin Zhu, Jing Li, Libin Huang, Rui Wang, Lan Peng, Min He, Yingmei Tang, Ping Chen, Cheng Lan, Xiaoqing Zhou, Lin Zhou, Ye Cheng, Linhao Zhang, Jingsun Jiang, Yanting Ye, Rui Wang, Yan He, Yan Liu, Hui Gong, Huifang Xiong, Liang Xia, Haiyan Xu, Bin Zhang, Rongfang Tu, Chun Du, Lujia Cui, Jinhang Gao, Zhiyin Huang, Chengwei Tang
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.