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Treatment of acute pancreatitis with protease inhibitors administered through intravenous infusion: an updated systematic review and meta-analysis.

Seta T, Noguchi Y, Shikata S, Nakayama T - BMC Gastroenterol (2014)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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.

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.

Conclusion: 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.

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Publication bias of trials reporting acute pancreatitis in patients given protease inhibitors. RD, Risk Difference; SE, Standard Error.
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Figure 4: Publication bias of trials reporting acute pancreatitis in patients given protease inhibitors. RD, Risk Difference; SE, Standard Error.

Mentions: Five trials (two for aprotinin [36,37] and three for gabexate mesilate [43,46,47]) reported that protease inhibitors were effective in preventing some complications. These complications included respiratory failure, renal failure, gastrointestinal bleeding, metabolic failure (details unknown), sepsis, or hypoxia [43,46]. Three studies defined complications as pancreatitis-related complications or unknown [33,37,47]. Overall results showed no significant risk reduction (low heterogeneity).


Treatment of acute pancreatitis with protease inhibitors administered through intravenous infusion: an updated systematic review and meta-analysis.

Seta T, Noguchi Y, Shikata S, Nakayama T - BMC Gastroenterol (2014)

Publication bias of trials reporting acute pancreatitis in patients given protease inhibitors. RD, Risk Difference; SE, Standard Error.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061927&req=5

Figure 4: Publication bias of trials reporting acute pancreatitis in patients given protease inhibitors. RD, Risk Difference; SE, Standard Error.
Mentions: Five trials (two for aprotinin [36,37] and three for gabexate mesilate [43,46,47]) reported that protease inhibitors were effective in preventing some complications. These complications included respiratory failure, renal failure, gastrointestinal bleeding, metabolic failure (details unknown), sepsis, or hypoxia [43,46]. Three studies defined complications as pancreatitis-related complications or unknown [33,37,47]. Overall results showed no significant risk reduction (low heterogeneity).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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.

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus