Ignite Creation Date:
2024-05-05 @ 11:42 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00112164
Status:
TERMINATED
Last Update Posted:
2014-03-13
First Post:
2005-05-27
Brief Title:
Activated Protein C to Treat Acute Lung Injuries
Sponsor:
University of California San Francisco
Organization:
University of California San Francisco
Study Overview
Official Title:
Prospective Randomized Phase II Clinical Trial of Activated Protein C Xigris Versus Placebo for the Treatment of Acute Lung Injury
Status:
TERMINATED
Status Verified Date:
2014-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Per recommendation of the NHLBI DSMB
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to test the efficacy of activated Protein C Xigris for improving clinical outcomes in individuals with acute lung injury ALI
Detailed Description:
BACKGROUND
The hypothesis that procoagulant and inflammatory mechanisms may have a dual role in tissue injury was tested in the phase III clinical trial of recombinant Xigris for severe sepsis Bernard 2001 There was a significant reduction in mortality from 30 to 24 in patients treated with Xigris However there is no information on the effect of Xigris on patients with sepsis and co-existing ALI Because Xigris is known to have both anti-coagulant and anti-inflammatory properties it is plausible that it may be effective at treating patients with ALI from pulmonary and non-pulmonary infectious causes There is also a good rationale for the hypothesis that Xigris may be effective at treating ALI from non-infectious causes In experimental lung injury from a non-infectious cause such as hyperoxia or a like acid-lung injury pro-coagulant mechanisms play a role in the pathogenesis of the ALI Eitzman 1996 Barazzone 1996 Furthermore research has shown that plasma-protein C deficiency occurs in almost all patients with ALI and reduced Protein C levels are associated with a higher mortality and more non-pulmonary organ system dysfunction even in patients with non-septic causes of ALI Ware 2003 Elevated levels of thrombomodulin a product of endothelial injury were measured in the plasma of all patients with ALI regardless of the clinical disorder associated with lung injury The elevations of thrombomodulin were much higher in edema fluid than in plasma suggesting that local activation and release of thrombomodulin had occurred probably from both epithelial and endothelial sources from the lung again supporting the hypothesis that a common pathway to lung injury may occur in both septic and non-septic causes of ALI In addition there is considerable evidence that the normal fibrinolytic mechanisms are impaired in the alveolar compartment in patients with ALI Elevated levels of plasminogen-activator-inhbitor-1 PAI-1 in the plasma of pulmonary edema fluid have a predictive value for identifying patients with ALI who are more likely to die than survive regardless of the clinical risk factors that predisposes the development of ALI Prabhakaran 2003 Thus this supports the rationale for testing Xigris as a treatment for patients with ALI regardless of the clinical disorder associated with the cause of the lung injury Since Xigris has both anti-coagulant and anti-inflammatory properties Esmon 2000 Grey 1994 this treatment could reverse both the intravascular and the extravascular lung injuries and allow the lung epithelial and endothelial barriers to recover from a functional breakdown of both barriers This study will evaluate the effects of the treatment of biochemical markers on alveolar epithelial injury
DESIGN NARRATIVE
Participants will be randomly assigned to receive either Xigris or saline placebo to be administered continuously for 96 hours Participants will be followed for 28 days regardless of whether the drug is stopped for an adverse event if the participant or physician decides to stop the drug if the participant is discharged from the hospital with unassisted breathing or until death
The hypothesis that procoagulant and inflammatory mechanisms may have a dual role in tissue injury was tested in the phase III clinical trial of recombinant Xigris for severe sepsis Bernard 2001 There was a significant reduction in mortality from 30 to 24 in patients treated with Xigris However there is no information on the effect of Xigris on patients with sepsis and co-existing ALI Because Xigris is known to have both anti-coagulant and anti-inflammatory properties it is plausible that it may be effective at treating patients with ALI from pulmonary and non-pulmonary infectious causes There is also a good rationale for the hypothesis that Xigris may be effective at treating ALI from non-infectious causes In experimental lung injury from a non-infectious cause such as hyperoxia or a like acid-lung injury pro-coagulant mechanisms play a role in the pathogenesis of the ALI Eitzman 1996 Barazzone 1996 Furthermore research has shown that plasma-protein C deficiency occurs in almost all patients with ALI and reduced Protein C levels are associated with a higher mortality and more non-pulmonary organ system dysfunction even in patients with non-septic causes of ALI Ware 2003 Elevated levels of thrombomodulin a product of endothelial injury were measured in the plasma of all patients with ALI regardless of the clinical disorder associated with lung injury The elevations of thrombomodulin were much higher in edema fluid than in plasma suggesting that local activation and release of thrombomodulin had occurred probably from both epithelial and endothelial sources from the lung again supporting the hypothesis that a common pathway to lung injury may occur in both septic and non-septic causes of ALI In addition there is considerable evidence that the normal fibrinolytic mechanisms are impaired in the alveolar compartment in patients with ALI Elevated levels of plasminogen-activator-inhbitor-1 PAI-1 in the plasma of pulmonary edema fluid have a predictive value for identifying patients with ALI who are more likely to die than survive regardless of the clinical risk factors that predisposes the development of ALI Prabhakaran 2003 Thus this supports the rationale for testing Xigris as a treatment for patients with ALI regardless of the clinical disorder associated with the cause of the lung injury Since Xigris has both anti-coagulant and anti-inflammatory properties Esmon 2000 Grey 1994 this treatment could reverse both the intravascular and the extravascular lung injuries and allow the lung epithelial and endothelial barriers to recover from a functional breakdown of both barriers This study will evaluate the effects of the treatment of biochemical markers on alveolar epithelial injury
DESIGN NARRATIVE
Participants will be randomly assigned to receive either Xigris or saline placebo to be administered continuously for 96 hours Participants will be followed for 28 days regardless of whether the drug is stopped for an adverse event if the participant or physician decides to stop the drug if the participant is discharged from the hospital with unassisted breathing or until death
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P50HL074005 | NIH | None | httpsreporternihgovquickSearchP50HL074005 |