Clinical trial NCT01017107: Activated Protein C in Severe Acute Pancreatitis
Official title: APCAP - Activated Protein C in Severe Acute Pancreatitis: A Double-blind Randomized Human Pilot Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Pancreatitis
Keywords: acute pancreatitis
treatment
organ failure
activated protein c
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
First posted: 2009-11-20
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Activated protein C (APC)has been shown to reduce mortality in severe sepsis(Bernard et al. 2001b). The clinical picture of severe acute pancreatitis (AP) is similar to that of sepsis. The investigators conducted a randomised double-blinded placebo-controlled pilot study in AP patients (16+16) with the same dose of APC that has been proven to be efficacious and safe in septic patients.

The aim of the study is to investigate whether the APC replacement therapy diminishes the occurrence and severity of organ dysfunction in patients with severe AP. The effect of APC on inflammatory and hemostatic parameters is also assessed.

Detailed description: The study started in 2003 and was finished in 2007. The study was registered in The Helsinki University Central Hospital study register in 2003.

Eligibility criteria: Inclusion Criteria:

* Admitted to hospital within 72 h of the onset of pain.
* Plasma amylase concentration more than three times the upper limit of the normal range and/or CT findings compatible with AP.
* Organ failure and \<48h of the onset of the first organ failure

Exclusion Criteria:

* HIV / B- or C hepatitis infection
* Pregnancy or breast feeding
* Active bleeding
* Increased risk of bleeding (thrombocytes \<30x10E9/L or INR\>3.0
* Gastrointestinal bleeding within 6 weeks or intracranial stroke within 3 months before the study
* Intravenous contrast extravasation or other signs (fresh hematoma) suggesting active hemorrhage within the pancreas or in the peripancreatic area on admission CT scan
* Use of antithrombin III within 12 h
* Use of acetylsalicylic acid or glycoprotein IIB/IA antagonist within 7 days / Thrombolytic therapy within 3 days
* Surgery requiring general or spinal anaesthesia within 12 h
* Previous pancreatic surgery
* Application of an epidural catheter within 48 h

Primary outcomes:
measure: The primary safety endpoint was the number of bleedings, and the primary efficacy endpoint was the change in SOFA between the start of the drug (day 0) and day 5.
timeFrame: 0-60 days
Secondary outcomes:
measure: Organ failure free days alive
timeFrame: 0-60 days
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
Study officials:
affiliation: Helsinki University Central Hospital
name: Ville Pettilä, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr; Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001 Mar 8;344(10):699-709. doi: 10.1056/NEJM200103083441001.
citation: Pettila V, Kyhala L, Kylanpaa ML, Leppaniemi A, Tallgren M, Markkola A, Puolakkainen P, Repo H, Kemppainen E. APCAP--activated protein C in acute pancreatitis: a double-blind randomized human pilot trial. Crit Care. 2010;14(4):R139. doi: 10.1186/cc9203. Epub 2010 Jul 27.