title: Recombinant human activated protein C as a disease modifier in severe acute pancreatitis: systematic review of current evidence.
abstract: BACKGROUND
  The severity of organ failure caused by acute pancreatitis (AP) is the most important determinant of mortality in the disease. Recombinant human activated protein C (Drotrecogin Alfa; Xigris, APC, rhAPC) is the first drug to show a decrease in all-cause mortality due to multiple organ failure caused by sepsis. As the systemic inflammatory response syndrome (SIRS) that causes organ failure in early AP is similar to that caused by severe sepsis, the use of rhAPC in the management of AP has been investigated in experimental and clinical studies which are collated in this review.
  
  
  METHODS
  A literature review of published material identified from MEDLINE and EMBASE databases, for the period from January 1985 to January 2011, reporting rhAPC usage in AP.
  
  
  RESULTS
  3 of 4 experimental studies reported an improvement in outcome in animals with AP given rhAPC. The clinical randomized trial showed no improvement in outcome in the treatment arm.
  
  
  CONCLUSIONS
  The experimental evidence of disease amelioration in AP following intervention with rhAPC has not translated to the small clinical RCT. Given that there were only 16 patients in the treatment arm, further clinical evaluation is justified.
authors.affiliation: Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Miranda
authors.forename: Benoy I
authors.initials: BI
authors.lastname: Babu
authors.forename: Ajith K
authors.initials: AK
authors.lastname: Siriwardena
mesh_terms: D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D016239:MEDLINE; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000209:etiology; D010195:Pancreatitis / Q000150:complications / Q000188:drug therapy*; D011486:Protein C / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D011994:Recombinant Proteins / Q000627:therapeutic use; D057170:Translational Research, Biomedical; D017211:Treatment Failure
chemical_list: D005343:Fibrinolytic Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated