No abstract

Purpose Infected pancreatic necrosis (IPN) is a highly morbid complication of acute necrotising pancreatitis (ANP). Since there is evidence of early-onset immunosuppression in acute pancreatitis, immune enhancement may be a therapeutic option. This trial aimed to evaluate whether early immune-enhancing Thymosin alpha 1 (Tα1) treatment reduces the incidence of IPN in patients with predicted severe ANP. Methods We conducted a multicentre, double-blind, randomised, placebo-controlled trial involving ANP patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 8 and a computed tomography (CT) severity score ≥ 5 admitted within 7 days of the advent of symptoms. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebos (normal saline). The primary outcome was the development of IPN during the index admission. Results A total of 508 patients were randomised, of whom 254 were assigned to receive Tα1 and 254 placebo. The vast majority of the participants required admission to the intensive care unit (ICU) (479/508, 94.3%). During the index admission, 40/254(15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95% CI − 7.4 to 5.1%]; p = 0.48). The results were similar across four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15%), bleeding (6.3% vs. 3.5%), and gastrointestinal fistula (2% vs. 2.4%). Conclusion The immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-022-06745-7.

Background: Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease with multiple etiologies. The prevalence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has been increasing in recent years. It is reported that early triglyceride (TG) levels were associated with the severity of the disease, and TG- lowering therapies, including medical treatment and blood purification, may impact the clinical outcomes. However, there is no consensus regarding the optimal TG-lowering therapy, and clinical practice varies greatly among different centers. Our objective is to evaluate the TG-lowering effects of different therapies and their impact on clinical outcomes in HTG-AP patients with worrisome features.Methods: This is a multicenter, observational, prospective cohort study. A total of approximately 300 patients with HTG-AP with worrisome features are planned to be enrolled. The primary objective of the study is to evaluate the relationship between TG decline and the evolution of organ failure, and patients will be dichotomized depending on the rate of TG decline. The primary outcome is organ failure (OF) free days to 14 days after enrollment. Secondary outcomes include new-onset organ failure, new-onset multiple-organ failure (MOF), new-onset persistent organ failure (POF), new receipt of organ support, requirement of ICU admission, ICU free days to day 14, hospital free days to day 14, 60-day mortality, AP severity grade (Based on the Revised Atlanta Classification), and incidence of systemic and local complications. Generalized linear model (GLM), Fine and Gray competing risk regression, and propensity score matching will be used for statistical analysis.Discussion: Results of this study will reveal the current practice of TG-lowering therapy in HTG-AP and provide necessary data for future trials.