Condition category
Respiratory
Date applied
22/11/2006
Date assigned
22/11/2006
Last edited
19/03/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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

http://www.vumc.nl/english/

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

Results - basic reporting

Publication summary

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24632673

Publication citations

  1. 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.

Additional files

Editorial Notes