Contact information
Type
Scientific
Primary contact
Dr A Beishuizen
ORCID ID
Contact details
VU Medical Center
Department of Intensive Care
P.O. Box 7057
Amsterdam
1007 MB
Netherlands
+31(0)20 444 4444
cornet@vumc.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NTR745
Study information
Scientific title
Acronym
INFALI
Study hypothesis
We 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
Ethics approval received from the local medical ethics committee
Study design
Randomised, multicentre, single-blinded, placebo controlled, parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Acute lung injury, acute respiratory distress syndrome
Intervention
After 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 type
Drug
Phase
Not Specified
Drug names
Activated Protein C (aPC)
Primary outcome measure
67-Gallium Pulmonary Leak Index (PLI).
Secondary outcome measures
1. 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 trial start date
01/09/2006
Overall trial end date
01/09/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. 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
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
106
Participant exclusion criteria
1. 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
Recruitment start date
01/09/2006
Recruitment end date
01/09/2008
Locations
Countries of recruitment
Netherlands
Trial participating centre
VU Medical Center
Amsterdam
1007 MB
Netherlands
Sponsor information
Organisation
Vrije University Medical Center (VUMC) (The Netherlands)
Sponsor details
Department of Intensive Care
P.O. Box 7057
Amsterdam
1007 MB
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Added as of 24/06/2008:
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Lilly Nederland B.V. (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24632673
Publication citations
-
Results
Cornet AD, Groeneveld AB, Hofstra JJ, Vlaar AP, Tuinman PR, van Lingen A, Levi M, Girbes AR, Schultz MJ, Beishuizen A, Recombinant human activated protein C in the treatment of acute respiratory distress syndrome: a randomized clinical trial., PLoS ONE, 2014, 9, 3, e90983, doi: 10.1371/journal.pone.0090983.