Charles J Miranda1, James M Mason2, Benoy I Babu1, Aali J Sheen1, Jane M Eddleston3, Michael J Parker3, Philip Pemberton4, Ajith K Siriwardena5. 1. Hepatobiliary Surgical Unit, Manchester Royal Infirmary, Manchester, UK. 2. Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK. 3. Critical Care Unit, Manchester Royal Infirmary, Manchester, UK. 4. Specialist Assay Laboratory, Manchester Royal Infirmary, Manchester, UK. 5. Hepatobiliary Surgical Unit, Manchester Royal Infirmary, Manchester, UK. Electronic address: ajith.siriwardena@cmft.nhs.uk.
Abstract
OBJECTIVE: Patients with severe acute pancreatitis were excluded from major trials of human recombinant activated protein C (Xigris) because of concern about pancreatic haemorrhage although these individuals have an intense systemic inflammatory response that may benefit from treatment. The object of this study was to provide initial safety data evaluating Xigris in severe acute pancreatitis. DESIGN: Prospective clinical trial recruiting between November 2009 and October 2011. Patients received human recombinant activated protein C (Xigris) for 24 h by intravenous infusion (24 μg/kg/h) in addition to standard clinical care. A matched historical control group treated within the same hospital unit were used to compare outcomes. Of 166 consecutive admitted patients, 43 met the screening criteria for severe acute pancreatitis and 19 were recruited, all contributing to the analyses. RESULTS: Compared to historical controls, there were fewer bleeding events in the Xigris group although the finding did not reach significance (Xigris 0% vs. Control 21%, p = 0.13), similarly further intervention appeared less frequent (11% vs. 47%, p = 0.07) in the treatment group. Length of stay was shorter for patients receiving Xigris (19 vs. 41 days, p = 0.03) as was inotrope use (5% vs. 32%, p = 0.02); mortality and incidence of infections in both groups were similar. Biomarker protein C increased while IL-6 decreased following infusion. CONCLUSIONS: A 24-hr infusion of Xigris appears safe when used in patients with severe acute pancreatitis. TRIAL REGISTRATION: Eudract Number 2007-003635-23.
OBJECTIVE:Patients with severe acute pancreatitis were excluded from major trials of human recombinant activated protein C (Xigris) because of concern about pancreatic haemorrhage although these individuals have an intense systemic inflammatory response that may benefit from treatment. The object of this study was to provide initial safety data evaluating Xigris in severe acute pancreatitis. DESIGN: Prospective clinical trial recruiting between November 2009 and October 2011. Patients received human recombinant activated protein C (Xigris) for 24 h by intravenous infusion (24 μg/kg/h) in addition to standard clinical care. A matched historical control group treated within the same hospital unit were used to compare outcomes. Of 166 consecutive admitted patients, 43 met the screening criteria for severe acute pancreatitis and 19 were recruited, all contributing to the analyses. RESULTS: Compared to historical controls, there were fewer bleeding events in the Xigris group although the finding did not reach significance (Xigris 0% vs. Control 21%, p = 0.13), similarly further intervention appeared less frequent (11% vs. 47%, p = 0.07) in the treatment group. Length of stay was shorter for patients receiving Xigris (19 vs. 41 days, p = 0.03) as was inotrope use (5% vs. 32%, p = 0.02); mortality and incidence of infections in both groups were similar. Biomarker protein C increased while IL-6 decreased following infusion. CONCLUSIONS: A 24-hr infusion of Xigris appears safe when used in patients with severe acute pancreatitis. TRIAL REGISTRATION: Eudract Number 2007-003635-23.