Activated protein C versus placebo in the treatment of INFlammatory or infectious Acute Lung Injury/acute respiratory distress syndrome (INFALI): a pathophysiological study on pulmonary microvascular permeability, apoptosis, inflammation and coagulation

ISRCTN ISRCTN52566874
DOI https://doi.org/10.1186/ISRCTN52566874
Secondary identifying numbers NTR745
Submission date
22/11/2006
Registration date
22/11/2006
Last edited
19/03/2014
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr A Beishuizen
Scientific

VU Medical Center
Department of Intensive Care
P.O. Box 7057
Amsterdam
1007 MB
Netherlands

Phone +31(0)20 444 4444
Email cornet@vumc.nl

Study information

Study designRandomised, multicentre, single-blinded, placebo controlled, parallel group trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific title
Study acronymINFALI
Study objectivesWe hypothesise that systemic activated Protein C (aPC) will benefit patients with Acute Lung Injury (ALI)/ Acute Respiratory Distress Syndrome (ARDS), as caused by inflammatory as well as infectious disorders, in terms of gas exchange, edema and capillary leak in these lungs, as well as in ventilator-days (duration of mechanical ventilation) or change in ventilatory mode.

Please note that as of 24/06/2008 more details on the sources of funding have been added to this record (i.e., funding now confirmed). This can be seen below in the sources of funding section.
Ethics approval(s)Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studiedAcute lung injury, acute respiratory distress syndrome
InterventionAfter stratification patients will be randomly assigned to the aPC (24 mcg/kg/hr during [in total] 96 hours) or placebo group.
1. On day one and five a 67-Ga pulmonary leak index and a computed tomography (CT)-thorax will be performed
2. In mechanically ventilated patients: mini-broncho alveloar lavage (mini-BAL) every second day
3. Day one to five, seven, nine, 11, 13, 15 blood samples and a chest X-ray
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Activated Protein C (aPC)
Primary outcome measure67-Gallium Pulmonary Leak Index (PLI).
Secondary outcome measures1. Lung injury score
2. Inflammatory mediators/biomarkers (blood, mini-BAL)
3. Coagulation and fibrinolysis markers (blood, mini-BAL)
4. Apoptosis markers (blood, mini-BAL)
5. Mortality
6. Extra-vascular lung water
7. Gas exchange (compliance, partial pressure of oxygen in arterial blood [PaO2]/fraction of inspired oxygen [FiO2])
8. Radiographic abnormalities (X-ray, CT)
9. Change of ventilatory mode (non-invasive versus invasive)
10. Duration of mechanical ventilation
Overall study start date01/09/2006
Completion date01/09/2008

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexNot Specified
Target number of participants106
Key inclusion criteria1. Age 18 to 75 years
2. Weight less than 135 kg
3. Recent onset (less than 24 hours) of ALI/ARDS, according to the American/European consensus criteria
4. ALI/ARDS due to severe sepsis reflecting single organ failure
Key exclusion criteria1. Acute Physiology And Chronic Health Evaluation (APACHE II) score: 25 and more
2. Two or more failing organs
3. Thrombocyte count less than 30 x 10^9/l
4. Any major surgery within 12 hours before inclusion
5. Trauma patients at increased risk of bleeding
6. Acute bleeding
7. A history of severe head trauma that required hospitalisation, intracranial surgery, or stroke within three months of study entry
8. Known intracranial abnormality such as aneurysms, tumor, arterio-venous malformation
9. Known hypercoagulability:
9.1. Resistance to protein C
9.2. Hereditary deficiency of protein C, protein S, or anti-thrombin
9.3. Presence of anticardiolipin antibody, antiphospholipid antibody, lupus anticoagulant or homocystinaemia
9.4. Recently documented (within three months of study entry) or highly suspected deep vein thrombosis or pulmonary embolism
10. A history of congenital bleeding diasthesis
11. Expected life expectancy less than 28 days (moribund state)
12. Preterminal illness
13. Pregnancy or breast feeding
14. Known portal hypertension with liver cirrhosis, oesophageal varices or both
15. Epidural catheter
16. Body weight more than 135 kg
17. Chronic renal insufficiency
18. Participation in another clinical trial
19. Patients with immune system impairment:
19.1. Human immunodeficiency virus (HIV)-infected patients (CD4+ less than 50/ml)
19.2. After bone-marrow, lung, liver, pancreas or small-bowel transplantation and treated with immunosuppressive therapy
Date of first enrolment01/09/2006
Date of final enrolment01/09/2008

Locations

Countries of recruitment

  • Netherlands

Study participating centre

VU Medical Center
Amsterdam
1007 MB
Netherlands

Sponsor information

Vrije University Medical Center (VUMC) (The Netherlands)
Hospital/treatment centre

Department of Intensive Care
P.O. Box 7057
Amsterdam
1007 MB
Netherlands

Website http://www.vumc.nl/english/
ROR logo "ROR" https://ror.org/00q6h8f30

Funders

Funder type

Industry

Added as of 24/06/2008:

No information available

Lilly Nederland B.V. (The Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 14/03/2014 Yes No