A single center randomized double blind controlled trial of pentoxifylline in acute pancreatitis: Challenges and opportunities.

OBJECTIVES: Despite substantial morbidity and mortality associated with acute pancreatitis (AP), only one small randomized controlled drug trial (RCT) is available in the past few decades from the United States. Hence, we conducted a single-center, double-blind, placebo-controlled RCT of pentoxifylline in AP. METHODS: A total of 9 doses of oral pentoxifylline 400 mg or placebo tablet, three times daily, was administered within 72 h of diagnosis, using randomization blocks by pharmacy. Primary outcome was a composite outcome including any of the following: death, peripancreatic and/or pancreatic necrosis, infected pancreatic necrosis, persistent organ failure, persistent systemic inflammatory response syndrome, hospital stay longer than 4 days, need for intensive care, and need for intervention for necrosis. RESULTS: Between July 7, 2015, and April 4, 2017, we identified 685 patients with AP, 233 met eligibility criteria and 176 were approached for the study. Of these, 91 (51.7%) declined and finally 45 in pentoxifylline group and 38 in placebo group (83 total) were compared. There were no significant differences in primary outcome (27 [60.0%] vs 15 [39.5%]; P = .06). Pentoxifylline group was not associated with any benefit, but withlonger stay (42% vs. 21%; P = .04) and higher readmission rates (16 %vs 3%; P = .047). CONCLUSIONS: We could not demonstrate superiority of pentoxifylline over placebo. Smaller sample size and inclusion of all types of severity might be the reasons for lack of efficacy. The challenges observed in the present study indicate that, in order to conduct a successful drug trial in AP, a multi center collaboration is essential.

Pentoxifylline Treatment in Severe Acute Pancreatitis: A Pilot, Double-Blind, Placebo-Controlled, Randomized Trial.

In acute pancreatitis (AP) tumor necrosis factor-α mediates multi-organ failure; in animal models its blockade with pentoxifylline ameliorates AP. The efficacy of pentoxifylline in predicted severe AP (pSAP) was tested in a double-blinded, randomized, control trial. Twenty-eight patients with pSAP were randomized within 72 hours of diagnosis to pentoxifylline or placebo. Baseline characteristics were similar in both groups. The pentoxifylline group had fewer intensive care unit admissions and shorter intensive care unit and hospital stays of longer than 4 days (all P < .05). Patients receiving pentoxifylline had no adverse effects. Pentoxifylline within 72 hours of pSAP is safe; a larger study of pentoxifylline in AP is needed to confirm efficacy. ClinicalTrials.gov number: NCT01292005.