Severe acute pancreatitis in man (with an APACHE II score of = 15) appears to carry a considerably higher risk of death when compared to general critical care patients with similar APACHE II scores. Current concepts of the pathophysiology of pancreatic necrosis suggest that disease progression is related to early activation of microvascular thrombotic pathways thus a theoretical case can be made for the use of activated protein C, early in the disease course of this illness Me
Conditions
Interventions
Trade Name: Xigris
Product Name: Xigris
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
Central Manchester and Manchester Children's Hospitals NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Acute pancreatitis – defined as acute abdominal pain with a threefold elevation of serum amylase or a twofold elevation of serum lipase. 2. Severe disease – defined as an APACHE II score of = 15 on admission to hospital together with a logistic organ dysfunction score of = 2 within the first 24 hours of admission to hospital. 3. Early disease – defined as being within 72 hours of onset of severe pain. 4. No clinical evidence of haemorrhage 5. Patients with no prior history of bleeding duodenal ulcer, haemorrhagic stroke or other haemorrhagic diathesis. 6. Patients not taking warfarin or other anticoagulant medication. 7. Patients without evidence of end-stage renal disease 8. Patients who are not pregnant or lactating. 9. Over 18 years of age. 10. No surgery or endoscopic retrograde cholangiopancreatography (ERCP) within the previous 30 days. 11. Patients able to give informed consent (or complying with current United Kingdom criteria for consent in critical care unit trials). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Inability to give consent. 2. Non-severe acute pancreatitis – defined as an APACHE II score of < 15 on admission to hospital. 3. Later presentation: in excess of 72 hours after onset of severe pain. 4. Clinical evidence of haemorrhage. 5. Patients with a prior history of bleeding duodenal ulcer, haemorrhagic stroke or other haemorrhagic diathesis. 6. Patients taking warfarin or other anticoagulant medication. Thrombocytopenia, coagulopathy. 7. Patients with evidence of end-stage renal disease. Patients with liver disease. 8. Under 18 years of age. 9. Surgery or ERCP within the previous 30 days. 10. Patients who may be pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to undertake a preliminary evaluation of the role of human recombinant activated protein C administered early in the disease course of human severe acute pancreatitis. The principal end-points are assessment of safety of treatment and assessment of effect of intervention on markers of the coagulation and inflammatory response. ;Secondary Objective: Interim analysis may indicate the feasibility or otherwise of a preliminary health economic analysis. Given that clinical experience with the use of xigris in severe acute pancreatitis is extremely limited, the proposed study will provided valuable baseline information that will help in two key areas: defining the nature of the acute pancreatitis population who may benefit from treatment with xigris and assessing the risk-benefit balance of intervention with xigris.; Primary end point(s): Primary endpoints The primary objective of this study is to undertake a preliminary evaluation of the role of human recombinant activated protein C administered early in the disease course of human severe acute pancreatitis. The principal end-points are assessment of safety of treatment and assessment of effect of intervention on specific markers of coagulation, in particular the Protein C response. Primary endpoint - clinical adverse event assessment 1. All bleeding events 2. Serious bleeding events. These are defined as per the PROWESS trial criteria as follows: any intracranial haemorrhage, any life-threatening bleed, any bleeding event requiring the administration of = 3 units of packed red blood cells per day for 2 consecutive days or any bleeding event assessed as a serious adverse event. 3. Thrombotic events – Any events observed (and recorded by the patients’ clinicians) will be noted. Any serious adverse events will be reported to the Eli Lilly | — |
Countries
United Kingdom
Outcome results
None listed