APCAP - activated protein C in acute pancreatitis: a double-blind randomized human pilot trial

Abstract

IntroductionPrevious 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.MethodsA prospective double blind randomized pilot study was use. The study occurred in one university hospital tertiary intensive care unit (ICU) with eight beds. The patients were chosen according to the following inclusion criteria: 1) Those admitted to the hospital < 96 h from the onset of pain, 2) Those who had a three-fold increase in serum amylase over normal upper range or/and in whom computed tomography (CT) verification of SAP was noted, 3) Those who had one or more organ dysfunction (OD), and 4) Those in whom less than 48 hours had passed since their 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. The intervention consisted of APC (N = 16) administered intravenously for 96 hours with a dose of 24 μg/kg/hour or placebo (N = 16) with a similar infusion rate. 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.ResultsNo serious bleeding was 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 to +5.3). Treatment with APC was associated with an 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 the hospital were detected.ConclusionsNo serious bleeding or differences in the evolution of MOD were detected between APC and the placebo. Instead we found an increase in serum bilirubin in the APC group compared to the placebo group in patients with SAP.Trial registrationClinicalTrials.gov NCT01017107.

Role of Thrombophilia in Splanchnic Venous Thrombosis in Acute Pancreatitis

“…Previous studies have reported that systemic activation of the coagulation system commonly occurs in over half of the critically ill patients with severe AP [12]. Proteins C and S, and AT III deficiencies were found in 23.8%, 33.3%, and 31.0% of patients respectively, similar to previous studies [12,[23][24][25]. Deficiency of these natural anticoagulants occurs as part of the systemic inflammatory response.…”

Meta-analysis of early nutrition: the benefits of enteral feeding compared to a nil per os diet not only in severe, but also in mild and moderate acute pancreatitis

“…Thirty-three articles (21 articles containing patients suffering from SAP as well as 12 articles with MAP patients) were selected. They contained two nonrandomized and 31 randomized controlled clinical trials (Table 2) [16][17][18][19][20][21][22][23][24][25][26][27]29,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. Finally, statistical analyses were performed on data from articles where both EN and NPO groups were presented, the trial was randomized, and the relevant data were available.…”

Early Management of Severe Acute Pancreatitis

“…However, a recent randomized, double-blind, placebo-controlled pilot trial using APC in ICU patients with SAP did not find any difference in SOFA scores, ventilator-free days, renal replacement-free days, vasopressor-free days, or days alive outside ICU between APC-treated and placebo-treated patients. No increase in bleeding-related complications was seen in APC-treated patients; however, these patients had increased levels of serum bilirubin in [52].…”