Evaluation of Pirfenidone for Recurrent Acute Pancreatitis: Protocol for a Randomized Trial

Recurrent acute pancreatitis (RAP) is defined as a syndrome of two or more episodes of acute pancreatitis (AP), with a period of resolution in between. Management of RAP is largely supportive, with no available drug therapy to prevent recurrence or progression to chronic pancreatitis (CP). Our preclinical data suggest that pirfenidone can improve parameters of RAP and decrease progression to CP. Therefore, we decided to conduct a pilot trial to evaluate pirfenidone in patients with RAP.

We have designed a double-blinded, multicenter, randomized, pilot clinical trial involving 60 patients. Patients with at least two diagnosed episodes of AP, separated by at least 3 mo, will be included in the trial. Patients with ongoing or recent AP (<30 d) or evidence of CP on cross-sectional imaging or endoscopic ultrasound will be excluded. Patients will be randomized to receive either placebo or pirfenidone in a 1:1 ratio. Treatment will be continued for 6 mo, with a follow-up period of up to 18 mo. The primary end points include completion of the treatment protocol and development of any grade III/IV adverse events. Exploratory secondary end points include number and severity of AP episodes, quality of life assessments, patient-reported outcome score, and progression to CP assessed via secretin MRCP, fecal elastase, and HbA1C testing.

There is an urgent need to identify novel therapies for RAP. Results of this pilot clinical trial may serve as the basis for a larger study evaluating the efficacy of pirfenidone in patients with RAP.

Currently enrolling (NCT06253117).