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Completed

NCT Number: NCT00943267

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

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.

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Key information

Conditions

Pneumonia Infections Lipopolysaccharides Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections

Age range

18 year–35 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Academic Medical Center/ University of Amsterdam

Amsterdam, 1100DD, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Drotrecogin alpha

Drug

Drotrecogin alpha is given intrabronchially by bronchoscopy at t=0

Saline (NaCl 0.9%)

Drug

Normal saline is given intrabronchially by bronchoscopy at t=0

Endotoxin

Drug

Endotoxin (4 ng/kg body weight) is given intrabronchially in one subsegment at t=0

Bronchoscopy

Procedure

Bronchoscopies are performed at t=0 (for instillation of LPS and Drotrecogin alpha) and at t=6 (for performing a bronchoalveolar lavage)

blood sampling

Procedure

Blood sampling is done by venapuncture at t=0 and t=6

Primary outcomes

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

    Time frame: 1 year

Secondary outcomes

  1. 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

Sponsors and collaborators

Lead sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Other

Registry information

Official study title

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

Important dates

Study start
2008
Primary completion
2010
Study completion
2011
First posted
Jul 22, 2009
Registry last updated
Mar 16, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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