Dataset Information

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

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.

SUBMITTER: Liu KD

PROVIDER: S-EPMC2542435 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Liu Kathleen D KD Levitt Joseph J Zhuo Hanjing H Kallet Richard H RH Brady Sandra S Steingrub Jay J Tidswell Mark M Siegel Mark D MD Soto Graciela G Peterson Michael W MW Chesnutt Mark S MS Phillips Charles C Weinacker Ann A Thompson B Taylor BT Eisner Mark D MD Matthay Michael A MA

American journal of respiratory and critical care medicine 20080619 6

<h4>Rationale</h4>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.<h4>Objectives</h4>To test the efficacy of activated protein C (APC) as a therapy for patients with ALI.<h4>Methods</h4>Eligible subjects were critically ill patients who met the American/European consensus criteria f ...[more]

PMID: 18565951

Similar Datasets

Project description:ObjectiveTo determine whether electronic health record alerts for acute kidney injury would improve patient outcomes of mortality, dialysis, and progression of acute kidney injury.DesignDouble blinded, multicenter, parallel, randomized controlled trial.SettingSix hospitals (four teaching and two non-teaching) in the Yale New Haven Health System in Connecticut and Rhode Island, US, ranging from small community hospitals to large tertiary care centers.Participants6030 adult inpatients with acute kidney injury, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria.InterventionsAn electronic health record based "pop-up" alert for acute kidney injury with an associated acute kidney injury order set upon provider opening of the patient's medical record.Main outcome measuresA composite of progression of acute kidney injury, receipt of dialysis, or death within 14 days of randomization. Prespecified secondary outcomes included outcomes at each hospital and frequency of various care practices for acute kidney injury.Results6030 patients were randomized over 22 months. The primary outcome occurred in 653 (21.3%) of 3059 patients with an alert and in 622 (20.9%) of 2971 patients receiving usual care (relative risk 1.02, 95% confidence interval 0.93 to 1.13, P=0.67). Analysis by each hospital showed worse outcomes in the two non-teaching hospitals (n=765, 13%), where alerts were associated with a higher risk of the primary outcome (relative risk 1.49, 95% confidence interval 1.12 to 1.98, P=0.006). More deaths occurred at these centers (15.6% in the alert group v 8.6% in the usual care group, P=0.003). Certain acute kidney injury care practices were increased in the alert group but did not appear to mediate these outcomes.ConclusionsAlerts did not reduce the risk of our primary outcome among patients in hospital with acute kidney injury. The heterogeneity of effect across clinical centers should lead to a re-evaluation of existing alerting systems for acute kidney injury.Trial registrationClinicalTrials.gov NCT02753751.

Dataset Information

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

Rationale

Objectives

Methods

Measurements and main results

Conclusions

Publications

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

Similar Datasets

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