NCT00943267

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
52

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Oct 2008

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2008

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

July 21, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 22, 2009

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2010

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2011

Completed
Last Updated

March 16, 2011

Status Verified

July 1, 2009

Enrollment Period

1.8 years

First QC Date

July 21, 2009

Last Update Submit

March 15, 2011

Conditions

PneumoniaLipopolysaccharides

Keywords

Activated Protein CLipopolysaccharidesInflammation, Pulmonary

Outcome Measures

Primary Outcomes (1)

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

    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

    1 year

Study Arms (2)

Activated protein C

EXPERIMENTAL
Drug: Drotrecogin alphaDrug: EndotoxinProcedure: BronchoscopyProcedure: Blood sampling

Saline

PLACEBO COMPARATOR
Drug: Saline (NaCl 0.9%)Drug: EndotoxinProcedure: BronchoscopyProcedure: Blood sampling

Interventions

Drotrecogin alphaDRUG

Drotrecogin alpha is given intrabronchially by bronchoscopy at t=0

Activated protein C
Saline (NaCl 0.9%)DRUG

Normal saline is given intrabronchially by bronchoscopy at t=0

Saline
EndotoxinDRUG

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

Activated protein CSaline
BronchoscopyPROCEDURE

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

Activated protein CSaline
Blood samplingPROCEDURE

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

Activated protein CSaline

Eligibility Criteria

Age18 Years - 35 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Academic Medical Center/ University of Amsterdam

Amsterdam, 1100DD, Netherlands

Location

Related Publications (1)

  • 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.

    PMID: 23060625DERIVED

MeSH Terms

Conditions

Pneumonia

Interventions

Sodium ChlorideEndotoxinsBronchoscopyBlood Specimen Collection

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

ChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium CompoundsBacterial ToxinsToxins, BiologicalBiological FactorsDiagnostic Techniques, Respiratory SystemDiagnostic Techniques and ProceduresDiagnosisEndoscopyDiagnostic Techniques, SurgicalMinimally Invasive Surgical ProceduresSurgical Procedures, OperativePulmonary Surgical ProceduresThoracic Surgical ProceduresSpecimen HandlingClinical Laboratory TechniquesPuncturesInvestigative Techniques

Study Officials

  • Tom Van der Poll, MD PhD

    AMC/UvA Amsterdam

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

July 21, 2009

First Posted

July 22, 2009

Study Start

October 1, 2008

Primary Completion

August 1, 2010

Study Completion

March 1, 2011

Last Updated

March 16, 2011

Record last verified: 2009-07

Locations

NL(1)