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News Newsfeeds APCAP - activated protein C in acute pancreatitis: a double-blind randomized human pilot trial
Written by Critical Care
Previous human studies have shown low activity of protein C (APC) in severe acute pancreatitis (SAP). This, together with the findings in animal models, suggests that activated protein C (APC) may protect against pancreatic injury and ameliorate the disease. We, therefore, evaluated its effect on multiple organ dysfunction (MOD) measured by the SOFA (Sequential Organ Failure Assessment) and on organ-failure-free days, and the safety of APC in SAP.
Methods:
Design: Prospective double blind randomized pilot study. Setting: One university hospital tertiary intensive care unit (ICU) with 8 beds. Patients: Inclusion criteria: 1. admitted to hospital <96 h from onset of pain, 2. a 3-fold increase in serum amylase over normal upper range or/and computed tomography (CT) verification of SAP, 3. one or more organ dysfunction (OD), and 4. <48 hours from the first OD. Of a total of 215 adult patients with SAP screened between June 2003 and August 2007, 158 fulfilled the study inclusion criteria. After exclusions 32 patients were randomized to the study. Intervention: APC (N=16) was administrated intravenously for 96 hours with a dose of 24 ug/kg/hour or placebo (N=16) with a similar infusion rate. Statistical analysis: The sample size for the study was calculated according to the primary end-point: the change in SOFA during study drug infusion (days 0 and 5). Comparisons between the study groups were performed using patient-related changes and calculation of difference in means [DIM, 95% CIs] and regarding categorical variables with Fisher's exact test. For all comparisons P< 0.05 was considered significant.
Results:
No serious bleedings were detected clinically or by CT- scans in either group. No significant difference in SOFA score change between the APC and placebo groups was found [difference in means (DIM) +2.3, 95% CI -0.7 - +5.3].Treatment with APC was associated with increase in serum levels of both total and conjugated bilirubin. No differences in ventilator-free days, in renal replacement therapy-free days, in vasopressor-free days, or in days alive outside hospital were detected.
Conclusions:
No serious bleedings or difference in the evolution of MOD were detected between APC and placebo. Instead we found an increase in serum bilirubin in the APC group compared to the placebo group in patients with SAP.Trial registration: ClinicalTrials.gov NCT01017107.
Monday, 26 July 2010 19:00
Introduction:Previous human studies have shown low activity of protein C (APC) in severe acute pancreatitis (SAP). This, together with the findings in animal models, suggests that activated protein C (APC) may protect against pancreatic injury and ameliorate the disease. We, therefore, evaluated its effect on multiple organ dysfunction (MOD) measured by the SOFA (Sequential Organ Failure Assessment) and on organ-failure-free days, and the safety of APC in SAP.
Methods:
Design: Prospective double blind randomized pilot study. Setting: One university hospital tertiary intensive care unit (ICU) with 8 beds. Patients: Inclusion criteria: 1. admitted to hospital <96 h from onset of pain, 2. a 3-fold increase in serum amylase over normal upper range or/and computed tomography (CT) verification of SAP, 3. one or more organ dysfunction (OD), and 4. <48 hours from the first OD. Of a total of 215 adult patients with SAP screened between June 2003 and August 2007, 158 fulfilled the study inclusion criteria. After exclusions 32 patients were randomized to the study. Intervention: APC (N=16) was administrated intravenously for 96 hours with a dose of 24 ug/kg/hour or placebo (N=16) with a similar infusion rate. Statistical analysis: The sample size for the study was calculated according to the primary end-point: the change in SOFA during study drug infusion (days 0 and 5). Comparisons between the study groups were performed using patient-related changes and calculation of difference in means [DIM, 95% CIs] and regarding categorical variables with Fisher's exact test. For all comparisons P< 0.05 was considered significant.
Results:
No serious bleedings were detected clinically or by CT- scans in either group. No significant difference in SOFA score change between the APC and placebo groups was found [difference in means (DIM) +2.3, 95% CI -0.7 - +5.3].Treatment with APC was associated with increase in serum levels of both total and conjugated bilirubin. No differences in ventilator-free days, in renal replacement therapy-free days, in vasopressor-free days, or in days alive outside hospital were detected.
Conclusions:
No serious bleedings or difference in the evolution of MOD were detected between APC and placebo. Instead we found an increase in serum bilirubin in the APC group compared to the placebo group in patients with SAP.Trial registration: ClinicalTrials.gov NCT01017107.
Authors: Ville Pettila
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