Clinical trial NCT00943267: Effect of Intrapulmonary Recombinant Human Activated Protein C (APC) on Coagulation and Inflammation After Lipopolysaccharide (LPS)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pneumonia
Lipopolysaccharides
Keywords: Activated Protein C
Lipopolysaccharides
Inflammation, Pulmonary
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2009-07-22
Enrollment: 52
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


Eligibility 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

Primary outcomes:
measure: To determine whether direct intrapulmonary delivery of rhAPC can inhibit LPS-induced lung inflammation, thereby avoiding systemic APC effects
timeFrame: 1 year
Secondary outcomes:
measure: 1. Neutrophil responses 2. Response of alveolar macrophages 3. Activation of the cytokine and chemokine network 4. Activation of coagulation and fibrinolysis
timeFrame: 1 year
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center/ University of Amsterdam
Study officials:
affiliation: AMC/UvA Amsterdam
name: Tom Van der Poll, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kager LM, de Boer JD, Bresser P, van der Zee JS, Zeerleder S, Meijers JC, van 't Veer C, van der Poll T. Intrabronchial activated protein C enhances lipopolysaccharide-induced pulmonary responses. Eur Respir J. 2013 Jul;42(1):188-97. doi: 10.1183/09031936.00057112. Epub 2012 Oct 11.