TY - JOUR
T1 - A single center randomized double blind controlled trial of pentoxifylline in acute pancreatitis
T2 - Challenges and opportunities
AU - Vege, Santhi Swaroop
AU - Horibe, Masayasu
AU - Chari, Suresh T.
AU - Clemens, Magdalen A.
AU - Loftus, Conor G.
AU - Enders, Felicity T.
N1 - Funding Information:
Research reported in this manuscript was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number 5R21DK101889-02 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 IAP and EPC
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Drug trial
KW - Peripancreatic necrosis and pancreatic necrosis
KW - Persistent organ failure
KW - Systemic inflammatory response syndrome
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U2 - 10.1016/j.pan.2020.09.023
DO - 10.1016/j.pan.2020.09.023
M3 - Article
C2 - 33036921
AN - SCOPUS:85092201614
SN - 1424-3903
VL - 20
SP - 1592
EP - 1597
JO - Pancreatology
JF - Pancreatology
IS - 8
ER -