PneumoniaNCT00943267
Effect of Intrapulmonary Recombinant Human Activated Protein C (APC) on Coagulation and Inflammation After Lipopolysaccharide (LPS)
A study testing Drotrecogin alpha, Saline (NaCl 0.9%) and Endotoxin in people with Pneumonia and Lipopolysaccharides, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Pneumonia, Lipopolysaccharides
- What is being tested?
- Drotrecogin alpha, Saline (NaCl 0.9%) and Endotoxin
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2008to Mar 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Academic Medical Center/ University of Amsterdam
Amsterdam, 1100DD
About this study
Official title: 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.
- Conditions
- Pneumonia, Lipopolysaccharides
- Being tested
- Drotrecogin alpha, Saline (NaCl 0.9%), Endotoxin, Bronchoscopy, Blood sampling
- Keywords
- Activated Protein C, Lipopolysaccharides, Inflammation, Pulmonary
- Medical subject headings
- Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drotrecogin alphaDrug
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
EndotoxinDrug
Endotoxin (4 ng/kg body weight) is given intrabronchially in one subsegment at t=0
BronchoscopyProcedure or surgery
Bronchoscopies are performed at t=0 (for instillation of LPS and Drotrecogin alpha) and at t=6 (for performing a bronchoalveolar lavage)
Blood samplingProcedure or surgery
Blood sampling is done by venapuncture at t=0 and t=6
| Study group | Role | What they receive |
|---|---|---|
| Activated protein C | Experimental | Not described Receives: Drug: Drotrecogin alpha; Drug: Endotoxin; Procedure: Bronchoscopy; Procedure: Blood sampling |
| Saline | Placebo comparator | Not described Receives: Drug: Saline (NaCl 0.9%); Drug: Endotoxin; Procedure: Bronchoscopy; Procedure: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine whether direct intrapulmonary delivery of rhAPC can inhibit LPS-induced lung inflammation, thereby avoiding systemic APC effects
Measured: 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
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2009 (estimated)
- Study startOct 2008
- Primary completionAug 2010
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Investigators
- Tom Van der Poll, MD PhD, Principal investigator, AMC/UvA Amsterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00943267
- Sponsor's protocol ID
- CEMM-APC-01
- Other IDs
- MEC 08/188
- Status last verified
- Jul 2009
- First submitted
- 21 Jul 2009
- Last updated
- 16 Mar 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 23060625
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Intrapulmonary Administration of Recombinant Human Activated Protein C on Local Coagulation and Inflammation After Bronchial Instillation of Lipopolysaccharide in Humans
- ClinicalTrials.gov ID
- NCT00943267
- Acronym / sponsor ID
- CEMM-APC-01
- Conditions
- Pneumonia, Lipopolysaccharides
- Keywords
- Activated Protein C, Lipopolysaccharides, Inflammation, Pulmonary
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- Oct 2008
- Primary completion
- Aug 2010 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 22 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Activated protein C | Experimental | Drug: Drotrecogin alpha, Drug: Endotoxin, Procedure: Bronchoscopy, Procedure: Blood sampling |
| Saline | Placebo comparator | Drug: Saline (NaCl 0.9%), Drug: Endotoxin, Procedure: Bronchoscopy, Procedure: Blood sampling |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Drotrecogin alphaDrotrecogin alpha is given intrabronchially by bronchoscopy at t=0 | Drug | Activated protein C |
| Saline (NaCl 0.9%)Normal saline is given intrabronchially by bronchoscopy at t=0 | Drug | Saline |
| EndotoxinEndotoxin (4 ng/kg body weight) is given intrabronchially in one subsegment at t=0 | Drug | Activated protein C, Saline |
| BronchoscopyBronchoscopies are performed at t=0 (for instillation of LPS and Drotrecogin alpha) and at t=6 (for performing a bronchoalveolar lavage) | Procedure or surgery | Activated protein C, Saline |
| Blood samplingBlood sampling is done by venapuncture at t=0 and t=6 | Procedure or surgery | Activated protein C, Saline |
Primary outcome
To determine whether direct intrapulmonary delivery of rhAPC can inhibit LPS-induced lung inflammation, thereby avoiding systemic APC effects
Time frame: 1 year
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2011.
- Derived from this study: PubMed 23060625Kager 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tom Van der Poll, MD PhD principal investigator
AMC/UvA Amsterdam
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Drotrecogin alpha, Saline (NaCl 0.9%) and Endotoxin in people with Pneumonia and Lipopolysaccharides, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00943267, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2011.