Effect of Intrapulmonary Recombinant Human Activated Protein C (APC) on Coagulation and Inflammation After Lipopolysaccharide (LPS)
Information source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pneumonia; Lipopolysaccharides
Intervention: Drotrecogin alpha (Drug); Saline (NaCl 0.9%) (Drug); Endotoxin (Drug); Bronchoscopy (Procedure); Blood sampling (Procedure)
Phase: N/A
Status: Completed
Sponsored by: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Official(s) and/or principal investigator(s): Tom Van der Poll, MD PhD, Principal Investigator, Affiliation: AMC/UvA Amsterdam
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.
Clinical Details
Official title: Effect of Intrapulmonary Administration of Recombinant Human Activated Protein C on Local Coagulation and Inflammation After Bronchial Instillation of Lipopolysaccharide in Humans
Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject)
Primary outcome: To determine whether direct intrapulmonary delivery of rhAPC can inhibit LPS-induced lung inflammation, thereby avoiding systemic APC effects
Secondary outcome: 1. Neutrophil responses 2. Response of alveolar macrophages 3. Activation of the cytokine and chemokine network 4. Activation of coagulation and fibrinolysis
Eligibility
Minimum age: 18 Years.
Maximum age: 35 Years.
Gender(s): Male.
Criteria:
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
Locations and Contacts
Academic Medical Center/ University of Amsterdam, Amsterdam 1100DD, Netherlands
Additional Information
Starting date: October 2008
Last updated: March 15, 2011
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