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Randomized Controlled Trial
. 2008 Sep 15;178(6):618-23.
doi: 10.1164/rccm.200803-419OC. Epub 2008 Jun 19.

Randomized clinical trial of activated protein C for the treatment of acute lung injury

Kathleen D Liu  1 , Joseph Levitt, Hanjing Zhuo, Richard H Kallet, Sandra Brady, Jay Steingrub, Mark Tidswell, Mark D Siegel, Graciela Soto, Michael W Peterson, Mark S Chesnutt, Charles Phillips, Ann Weinacker, B Taylor Thompson, Mark D Eisner, Michael A Matthay
Affiliations
Randomized Controlled Trial

Randomized clinical trial of activated protein C for the treatment of acute lung injury

Kathleen D Liu et al. Am J Respir Crit Care Med. .

Abstract

Rationale: Microvascular injury, inflammation, and coagulation play critical roles in the pathogenesis of acute lung injury (ALI). Plasma protein C levels are decreased in patients with acute lung injury and are associated with higher mortality and fewer ventilator-free days.

Objectives: To test the efficacy of activated protein C (APC) as a therapy for patients with ALI.

Methods: Eligible subjects were critically ill patients who met the American/European consensus criteria for ALI. Patients with severe sepsis and an APACHE II score of 25 or more were excluded. Participants were randomized to receive APC (24 microg/kg/h for 96 h) or placebo in a double-blind fashion within 72 hours of the onset of ALI. The primary endpoint was ventilator-free days.

Measurements and main results: APC increased plasma protein C levels (P = 0.002) and decreased pulmonary dead space fraction (P = 0.02). However, there was no statistically significant difference between patients receiving placebo (n = 38) or APC (n = 37) in the number of ventilator-free days (median [25-75% interquartile range]: 19 [0-24] vs. 19 [14-22], respectively; P = 0.78) or in 60-day mortality (5/38 vs. 5/37 patients, respectively; P = 1.0). There were no differences in the number of bleeding events between the two groups.

Conclusions: APC did not improve outcomes from ALI. The results of this trial do not support a large clinical trial of APC for ALI in the absence of severe sepsis and high disease severity.

Trial registration: ClinicalTrials.gov NCT00112164.

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Figures

<b>Figure 1.</b>
Figure 1.
Enrollment and outcomes. Patients may have had more than one reason for exclusion. The full list of exclusion criteria can be found in the online supplement. APACHE = Acute Physiology and Chronic Health Evaluation; APC = activated protein C.
<b>Figure 2.</b>
Figure 2.
Change in protein C levels by treatment group. The horizontal line within the box represents the median, the boxes encompasses the 25th–75th percentile, and the whiskers encompass the 10th–90th percentile (solid dot is an outlier). Units for protein C levels are % of normal, so the y axis represents the change in protein C levels expressed as % of normal. There is a difference in the change between baseline and Day 3 levels in the activated protein C (APC)–treated group, compared with the control group, P = 0.002.
See this image and copyright information in PMC

Comment in

References

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