Safety, tolerability and therapeutic efficacy of anti-inflammatory drug pirfenidone in acute pancreatitis patients: Protocol for a randomized pilot clinical trial.

Background: Acute Pancreatitis (AP) is a formidable disease with significant morbidity, mortality and healthcare expenditure. There is an emergent need to develop therapeutic agents for this disease as there are no targeted therapies available. We have recently demonstrated that pirfenidone can significantly decrease the severity of AP in animal models. Based on our preclinical findings, we decided to conduct a pilot trial to evaluate the safety, tolerability and efficacy of pirfenidone in patients with AP.

Methods: We have designed a multicenter, randomized, pilot clinical trial of 60 patients with blinded outcome assessment. All patients with AP, who present within 48 h of establishment of the diagnosis, will be screened for exclusion and inclusion criteria. Consenting patients will be randomized into pirfenidone or placebo within 48 h of the diagnosis of AP. The primary end points include decrease in PAN-PROMISE score after 72 h of initiation of drug, reduction in inflammatory markers, and development of serious adverse events. The secondary end points include changes in PAN-PROMISE score, discharge PASS score <60, development of composite outcome of new or worsening necrotizing pancreatitis on CT scan performed 5-7 days after admission, major infection or death, and readmissions and/or ER visits within 30 days and within 6 months after discharge.

Status: Currently enrolling (NCT05350371).

Conclusion: There is an urgent need to identify novel therapies for AP. This pilot clinical trial may become the basis of a larger study to analyze the efficacy of pirfenidone in patients with AP.