Patients with acute pancreatitis who received pentoxifylline had fewer ICU admissions and shorter ICU and hospital stays than placebo-treated controls, according to a small, randomized double-blind trial reported in Gastroenterology.
“We showed that a single-institution drug trial for acute pancreatitis is feasible and that pentoxifylline is safe, cheap, and might have efficacy,” wrote Dr. Santhi Vege and his associates at the Mayo Clinic in Rochester, Minn. “This sets the stage for a larger trial of this drug in all patients with acute pancreatitis, to realize the goal of finding an effective drug that can be given within 24 hours of diagnosis in any setting.”
Tumor necrosis factor–alpha is a key culprit in severe acute pancreatitis, including pancreatic and peripancreatic necrosis, systemic inflammatory response syndrome, and persistent organ failure, the researchers noted. Pentoxifylline is a nonselective phosphodiesterase inhibitor that has been found safe and effective in other TNF-alpha–mediated diseases such as acute alcoholic hepatitis, but few studies in humans have evaluated the drug for acute pancreatitis, they said (Gastroenterology 2015 June 22 [doi:10.1053/j.gastro.2015.04.019]). For their study, the investigators randomized 28 patients with predicted severe acute pancreatitis to either placebo or 400 mg pentoxifylline given orally at enrollment and then three times a day for 72 hours. Both groups also received standard of care treatments such as antibiotics and fluid therapy, and had comparable baseline characteristics including age, sex, body mass index, Acute Physiology and Chronic Health Evaluation scores, systemic inflammatory response syndrome scores, and inflammatory marker levels, the researchers said.
Significantly fewer patients who received pentoxifylline needed to stay in the hospital for more than 4 days (14% vs. 57% for the placebo group; P = .046), and the maximum length of ICU stay was 0 days for the intervention group, compared with 13 days for the control group (P = .03), the investigators reported. Analyses of several other outcome measures also favored pentoxifylline over placebo, but did not reach statistical significance in the small study, including the need for ICU transfer (0% for pentoxifylline patients vs. 28% of the placebo group; P = .098) and the median length of hospitalization (for pentoxifylline: 3 days, range 1-5 days; for placebo: 5 days; range 1-30 days; P = .06).
The treatment and control groups did not significantly differ in terms of levels of inflammatory markers, including circulating TNF-alpha, said the investigators. Differences in levels of TNF-alpha, interleukin-6, IL-8, and C-reactive protein “may be significant if the sample size is larger,” they added.
The exact mechanism by which pentoxifylline affects acute pancreatitis is unclear, but the production of pancreatic TNF-alpha peaks about 24-36 hours into an episode of the disease, so patients might benefit from receiving pentoxifylline sooner than the 72-hour window dictated by the study protocol, said Dr. Vege and his associates. “Initiating drug therapy within a few hours is challenging, although a 24-hour cutoff time may be feasible in appropriate settings,” they wrote.
A scholarly opportunity award from the Mayo Clinic helped fund the work. The investigators reported having no relevant financial conflicts of interest.
