Efficacy Study of CytoSorb Hemoperfusion Device on IL-6 Removal in ARDS/ALI Patients With Sepsis
The hypothesis of this study is use of CytoSorb hemoperfusion device as an adjunctive therapy to the standard of care in treating ARDS/ALI patients in the setting of sepsis will result in improved clearance of cytokines when compared to control patients receiving only the standard of care.
Acute Respiratory Distress Syndrome
Acute Lung Injury
Device: CytoSorb Hemoperfusion
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multi-Center, Efficacy Study of the MedaSorb CytoSorb™ Hemoperfusion Device as an Adjunctive Therapy in Subjects With Acute Respiratory Distress Syndrome (ARDS) or Acute Lung Injury (ALI) in the Setting of Sepsis|
- Relative IL-6 levels as a percent (%) of baseline will be lower in subjects receiving CytoSorb treatment in conjunction with the standard of care as compared to control subjects receiving only the standard of care for ARDS/ALI in the setting of sepsis. [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
- Ventilator Free Days, Reduction cytokines TNF-α, IL-1b, IL-10, CRP, 28-day all cause mortality, Oxygen Index (OI), P/F ratios, MODS scores [ Time Frame: 28 Days ] [ Designated as safety issue: No ]
|Study Start Date:||November 2007|
|Study Completion Date:||June 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
Device: CytoSorb Hemoperfusion
Mortality rates from acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) range from 38.5 to 65%, with the lower mortality in acute lung injury than in ARDS.
ARDS/ALI is most often seen as part of a systemic inflammatory response syndrome (SIRS), particularly systemic sepsis. The lung findings parallel the damage in other tissues, namely, widespread destruction of the capillary endothelium, extravasation of protein rich fluid and interstitial edema. The alveolar basement membrane becomes damaged and fluid leaks into the airspaces, reducing lung compliance and causing ventilation-perfusion mismatch.
The most important causes of ALI/ARDS are sepsis, pneumonia, major trauma, pulmonary aspiration, near drowning, burns, inhalation of toxic gases (e.g. ammonia), fat embolism, amniotic fluid embolism, eclampsia, drug intoxication (e.g. aspirin), radiation injury and mechanical ventilation. Cox and colleagues have demonstrated in an ovine model of ARDS that there is intense acute inflammation in the trachea and bronchi from 3 to 48h after injury, with accumulation of neutrophils, fibrin and other plasma proteins, and mucus in airway lumens. Immunostaining for multiple cytokines (interleukin-8 (IL-8), IL-1beta, IL-1alpha, tumor necrosis factor-alpha (TNF-alpha), and vascular endothelial growth factor (VEGF)) are found in airway mucous glands, and the release of cytokines into the airway lumen are considered potentially highly significant in the progression of injury.
The importance of cytokines is being increasingly realized in mechanical lung injury (a common cause of ALI/ARDS) associated with mechanical ventilation (MV). Here the pathway is identical with release of cytokines/chemokines which potentiate the extravasation, activation, and recruitment of leukocytes, causing ventilator-associated lung injury (VALI) and ventilator-induced lung injury (VILI). Moreover, VALI/VILI can perpetuate the chronic inflammatory response during ALI/ARDS and multiple organ dysfunction syndrome (MODS).
The purpose of this study is to evaluate the reduction of cytokines, using the CytoSorb device, on primary and secondary endpoints
Please refer to this study by its ClinicalTrials.gov identifier: NCT00559130
|Principal Investigator:||Martin K Kuhlmann, Prof. Dr.||Vivantes Klinikum|