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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00943267

Enrollment

Registered

2009-07-22

Start date

2008-10-31

Completion date

2011-03-31

Last updated

2011-03-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lipopolysaccharides, Pneumonia

Keywords

Activated Protein C, Lipopolysaccharides, Inflammation, Pulmonary

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.

Interventions

DRUGDrotrecogin alpha

Drotrecogin alpha is given intrabronchially by bronchoscopy at t=0

DRUGSaline (NaCl 0.9%)

Normal saline is given intrabronchially by bronchoscopy at t=0

DRUGEndotoxin

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

PROCEDUREBronchoscopy

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

PROCEDUREBlood sampling

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

MALE

Age

18 Years to 35 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

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

Secondary

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	1 year

Countries

Netherlands

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026