Clinical Trial: Activated Protein C to Treat Acute Lung Injuries

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Prospective, Randomized Phase II Clinical Trial of Activated Protein C (Xigris) Versus Placebo for the Treatment of Acute Lung Injury

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 Summary:

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
Sponsor: University of California, San Francisco

Current Primary Outcome: Number of ventilator-free days (measured at Day 28)

Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University of California, San Francisco

Dates:
Date Received: May 27, 2005
Date Started: January 2005
Date Completion:
Last Updated: March 11, 2014
Last Verified: March 2014