Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial

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.

Acute Pancreatitis: Diagnosis and Treatment

“…It is to be hoped these trials will be completed soon and that the international impetus for such trials will grow. New or repositioned drugs targeting pivotal disease mechanisms (see Table 1) are vital in this pursuit, as is reduced door-toneedle time, unlike in a recently reported negative trial of thymosin alpha 1 that featured a recruitment window of 7 days [267]. Establishing pipelines of double-blind, placebocontrolled, multicentre trials of drugs will bring the prospect of success closer, an imperative for affected patients.…”

Fire in the belly: A scoping review of the immunopathological mechanisms of acute pancreatitis

“…There is increasing interest in immune modulation for the management of pancreatitis, especially at the severe end of the spectrum. A recently published RCT (published following our literature search) compared thymosin alpha (an enhancer of cell-based immunity) with placebo in patients with predicted SAP ( 246 ); the primary outcome was development of infected pancreatic necrosis and the secondary outcomes included HLA-DR expression. In this study, participants were eligible for inclusion if they had had abdominal symptoms for up to 7 days.…”

Circulating monocytes in acute pancreatitis

“…Hypertriglyceridemia (HTG) is a highly prevalent form of dyslipidemia with major health concern (175). HTG is the third most common cause of AP globally (177) and is one of the most leading etiologies in Chinese AP cohorts (178)(179)(180)(181). Apart from elevated triglyceride levels, HTG-AP is also accompanied with maladjusted lipoprotein metabolism (177).…”