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

Not Applicable

Completed

• Conditions: Pneumonia; Lipopolysaccharides
• Interventions: Drug: Saline (NaCl 0.9%); Drug: Drotrecogin alpha; Drug: Endotoxin; Procedure: Bronchoscopy; Procedure: Blood sampling

• Registration Number: NCT00943267
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-10
• Status Verified: 2009-07
• Study First Submitted: 2009-07-21
• Study First Submitted QC: 2009-07-21
• Study First Posted: 2009-07-22
• Primary Completion: 2010-08
• Study Completion: 2011-03
• Last Update Submitted: 2011-03-15
• Last Update Posted: 2011-03-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 52

Inclusion Criteria

• Male, 18-35 years of age
• No clinically significant findings during physical examination and hematological and biochemical screening
• Normal spirometry and ECG
• Able to communicate well with the investigator and to comply with the requirements of the study
• No medication
• Written informed consent
• No smoking

Exclusion criteria:

• Known diseases
• A history of smoking within the last six months, or regular consumption of greater than three units of alcohol per day
• Administration of any investigational drug within 30 days of study initiation
• Donation of blood within 60 days, or loss of greater than 400 ml of blood within 12 weeks of study initiation
• History of enhanced bleeding tendency
• History of heparin-induced thrombocytopenia
• History of serious drug-related reactions, including hypersensitivity

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Saline	Saline (NaCl 0.9%)	-
Saline	Endotoxin	-
Activated protein C	Drotrecogin alpha	-
Activated protein C	Endotoxin	-
Activated protein C	Bronchoscopy	-
Activated protein C	Blood sampling	-
Saline	Bronchoscopy	-
Saline	Blood sampling	-

Primary Outcome Measures

Name	Time	Method
To determine whether direct intrapulmonary delivery of rhAPC can inhibit LPS-induced lung inflammation, thereby avoiding systemic APC effects	1 year

Secondary Outcome Measures

Name	Time	Method
1. Neutrophil responses 2. Response of alveolar macrophages 3. Activation of the cytokine and chemokine network 4. Activation of coagulation and fibrinolysis	1 year

Trial Locations

Locations (1)

Academic Medical Center/ University of Amsterdam; 🇳🇱 Amsterdam, Netherlands