Effect of Intrapulmonary Recombinant Human Activated Protein C (APC) on Coagulation and Inflammation After Lipopolysaccharide (LPS)
March 15, 2011 updated by: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
52
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Amsterdam, Netherlands, 1100DD
- Academic Medical Center/ University of Amsterdam
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 35 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Placebo Comparator: Saline
|
Endotoxin (4 ng/kg body weight) is given intrabronchially in one subsegment at t=0
Bronchoscopies are performed at t=0 (for instillation of LPS and Drotrecogin alpha) and at t=6 (for performing a bronchoalveolar lavage)
Blood sampling is done by venapuncture at t=0 and t=6
Normal saline is given intrabronchially by bronchoscopy at t=0
|
|
Experimental: Activated protein C
|
Drotrecogin alpha is given intrabronchially by bronchoscopy at t=0
Endotoxin (4 ng/kg body weight) is given intrabronchially in one subsegment at t=0
Bronchoscopies are performed at t=0 (for instillation of LPS and Drotrecogin alpha) and at t=6 (for performing a bronchoalveolar lavage)
Blood sampling is done by venapuncture at t=0 and t=6
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
To determine whether direct intrapulmonary delivery of rhAPC can inhibit LPS-induced lung inflammation, thereby avoiding systemic APC effects
Time Frame: 1 year
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
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
|
1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Tom Van der Poll, MD PhD, AMC/UvA Amsterdam
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2008
Primary Completion (Actual)
August 1, 2010
Study Completion (Actual)
March 1, 2011
Study Registration Dates
First Submitted
July 21, 2009
First Submitted That Met QC Criteria
July 21, 2009
First Posted (Estimate)
July 22, 2009
Study Record Updates
Last Update Posted (Estimate)
March 16, 2011
Last Update Submitted That Met QC Criteria
March 15, 2011
Last Verified
July 1, 2009
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CEMM-APC-01
- MEC 08/188
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.