title: Treatment of acute pancreatitis with protease inhibitors administered through intravenous infusion: an updated systematic review and meta-analysis.
abstract: BACKGROUND
  The intravenous use of protease inhibitors in patients with acute pancreatitis is still controversial. The purpose of this study was to evaluate the effectiveness of protease inhibitors intravenously administered to prevent pancreatitis-associated complications.
  
  
  METHODS
  We updated our previous meta-analysis with articles of randomized controlled trials published from January 1965 to March 2013 on the effectiveness of protease inhibitors for acute pancreatitis. A systematic search of PubMed, EMBASE, the Cochrane Library, and Japana Centra Revuo Medicina was conducted. In addition, Internet-based registries (ClinicalTrials.gov, controlled-trials.com, UMIN, JMACCT, and JAPIC) were used to search for on-going clinical trials. Furthermore, references of review articles and previously published meta-analyses were handsearched. The main outcome of interest was the overall mortality rate from acute pancreatitis.
  
  
  RESULTS
  Seventeen trials were selected for analysis. Overall, protease inhibitors did not achieve a significant risk reduction in mortality (pooled risk difference [RD], -0.02; 95% Confidence Interval [CI], -0.05 to 0.01; number needed to treat [NNT], 74.8) with low heterogeneity. A subgroup analysis in moderate to severe pancreatitis (defined by control mortality rate [CMR] >0.10) did not show a significant effect of protease inhibitors to prevent death (pooled RD, -0.03; 95% CI, -0.07 to 0.01; NNT, 1603.9) with low heterogeneity. An additional subgroup analysis of two trials with CMR >0.20 (i.e., low quality) revealed a significant risk reduction.
  
  
  CONCLUSIONS
  The present meta-analysis re-confirmed that there is no solid evidence that supports the intravenous use of protease inhibitors to prevent death due to acute pancreatitis.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Seta
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Noguchi
authors.forename: Satoru
authors.initials: S
authors.lastname: Shikata
authors.affiliation: Department of Health Informatics, Kyoto University School of Public Health, Yoshida-Konoe, Sakyo-ku, Kyoto, Kyoto 606-8501, Japan. t-nakayama@umin.ac.jp.
authors.forename: Takeo
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000208:Acute Disease; D007611:Aprotinin / Q000627:therapeutic use; D016670:Gabexate / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D010195:Pancreatitis / Q000188:drug therapy* / Q000401:mortality; D011480:Protease Inhibitors / Q000627:therapeutic use*; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D011480:Protease Inhibitors; D015842:Serine Proteinase Inhibitors; D016670:Gabexate; D007611:Aprotinin