NCT00943267

Effect of Intrapulmonary Recombinant Human Activated Protein C (APC) on Coagulation and Inflammation After Lipopolysaccharide (LPS)

Effect of Intrapulmonary Administration of Recombinant Human Activated Protein C on Local Coagulation and Inflammation After Bronchial Instillation of Lipopolysaccharide in Humans

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 52 (estimated)
• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Academic / Other
• Sex: Male
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

Summary

Recombinant human Activated Protein C (rhAPC) has been shown to reduce the mortality of patients with severe sepsis. The biological effects of APC are pleiotropic, and can be roughly divided in anticoagulant and cytoprotective effects. Lung infection and inflammation are associated with reduced bronchoalveolar levels of endogenous APC. Recent evidence derived from animal studies indicates that local administration of rAPC into the lungs exerts local anti-inflammatory and anticoagulant effects. In this study we propose to study the potential of locally administered APC, within a lung subsegment, to inhibit lipopolysaccharide (LPS) induced lung inflammation and coagulation in humans.

Conditions

• Pneumonia
• Lipopolysaccharides

Interventions

Type	Name	Description
DRUG	Drotrecogin alpha	Drotrecogin alpha is given intrabronchially by bronchoscopy at t=0
DRUG	Saline (NaCl 0.9%)	Normal saline is given intrabronchially by bronchoscopy at t=0
DRUG	Endotoxin	Endotoxin (4 ng/kg body weight) is given intrabronchially in one subsegment at t=0
PROCEDURE	Bronchoscopy	Bronchoscopies are performed at t=0 (for instillation of LPS and Drotrecogin alpha) and at t=6 (for performing a bronchoalveolar lavage)
PROCEDURE	Blood sampling	Blood sampling is done by venapuncture at t=0 and t=6

Timeline

• Start date: 2008-10-01
• Primary completion: 2010-08-01
• Completion: 2011-03-01
• First posted: 2009-07-22
• Last updated: 2011-03-16

Locations

1 site across 1 country: Netherlands