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
Protocol serial number	NTR745
Sponsor	Vrije University Medical Center (VUMC) (The Netherlands)
Funders	Added as of 24/06/2008:, Lilly Nederland B.V. (The Netherlands)

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

Primary study design	Interventional
Study design	Randomised, multicentre, single-blinded, placebo controlled, parallel group trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	INFALI
Study objectives	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(s)	Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Activated Protein C (aPC)
Primary outcome measure(s)	67-Gallium Pulmonary Leak Index (PLI).
Key secondary outcome measure(s)	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
Completion date	01/09/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target sample size at registration	106
Key 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
Key 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
Date of first enrolment	01/09/2006
Date of final enrolment	01/09/2008

Locations

Countries of recruitment

Netherlands

Study participating centre

VU Medical Center

Amsterdam
1007 MB
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not 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