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

This study has been completed.
Sponsor:
Information provided by:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT00943267
First received: July 21, 2009
Last updated: March 15, 2011
Last verified: July 2009
History of Changes

July 21, 2009
March 15, 2011
October 2008
August 2010   (final data collection date for primary outcome measure)
To determine whether direct intrapulmonary delivery of rhAPC can inhibit LPS-induced lung inflammation, thereby avoiding systemic APC effects [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00943267 on ClinicalTrials.gov Archive Site
1. Neutrophil responses 2. Response of alveolar macrophages 3. Activation of the cytokine and chemokine network 4. Activation of coagulation and fibrinolysis [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
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

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.
Not Provided
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
  • Pneumonia
  • Lipopolysaccharides
  • 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
  • Experimental: Activated protein C
    Interventions:
    • Drug: Drotrecogin alpha
    • Drug: Endotoxin
    • Procedure: Bronchoscopy
    • Procedure: Blood sampling
  • Placebo Comparator: Saline
    Interventions:
    • Drug: Saline (NaCl 0.9%)
    • Drug: Endotoxin
    • Procedure: Bronchoscopy
    • Procedure: Blood sampling
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
52
March 2011
August 2010   (final data collection date for primary outcome measure)

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
Male
18 Years to 35 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00943267
CEMM-APC-01, MEC 08/188
Yes
Tom van der Poll MD PhD, Center for Experimental Molecular Medicine, AMC-UvA, Amsterdam, The Netherlands
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Not Provided
Principal Investigator: Tom Van der Poll, MD PhD AMC/UvA Amsterdam
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
July 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP