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Randomized Controlled Trial
. 2014 Mar 14;9(3):e90983.
doi: 10.1371/journal.pone.0090983. eCollection 2014.

Recombinant human activated protein C in the treatment of acute respiratory distress syndrome: a randomized clinical trial

Alexander D Cornet  1 , A B Johan Groeneveld  2 , Jorrit J Hofstra  3 , Alexander P Vlaar  4 , Pieter R Tuinman  3 , Arthur van Lingen  5 , Marcel Levi  6 , Armand R J Girbes  7 , Marcus J Schultz  3 , Albertus Beishuizen  8
Affiliations
Randomized Controlled Trial

Recombinant human activated protein C in the treatment of acute respiratory distress syndrome: a randomized clinical trial

Alexander D Cornet et al. PLoS One. .

Abstract

Rationale: Pulmonary coagulopathy may play a pathogenetic role in acute respiratory distress syndrome (ARDS), by contributing to alveolocapillary inflammation and increased permeability. Recombinant human activated protein C (rh-APC) may inhibit this process and thereby improve patient outcome.

Methods: A prospective randomized, saline-controlled, single-blinded clinical trial was performed in the intensive care units of two university hospitals, and patients with ARDS were included within 24 h after meeting inclusion criteria.

Intervention: A 4-day course of intravenous rh-APC (24 mcg/kg/h) (n = 33) versus saline (n = 38).

Outcomes: The primary outcome parameter was the pulmonary leak index (PLI) of 67Gallium-transferrin as a measure of alveolocapillary permeability and secondary outcomes were disease severity scores and ventilator-free days, among others.

Results: Baseline characteristics were similar; in 87% of patients the PLI was above normal and in 90% mechanical or non-invasive ventilation was instituted at a median lung injury score of 2.5. There was no evidence that Rh-APC treatment affected the PLI or attenuated lung injury and sequential organ failure assessment scores. Mean ventilator-free days amounted to 14 (rh-APC) and 12 days (saline, P = 0.35). 28-day mortality was 6% in rh-APC- and 18% in saline-treated patients (P = 0.12). There was no difference in bleeding events. The study was prematurely discontinued because rh-APC was withdrawn from the market.

Conclusion: There is no evidence that treatment with intravenous rh-APC during 4 days for infectious or inflammatory ARDS ameliorates increased alveolocapillary permeability or the clinical course of ARDS patients. We cannot exclude underpowering.

Trial registration: Nederlands Trial Register ISRCTN 52566874.

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Conflict of interest statement

Competing Interests: The study received funding by Eli Lilly Inc. (Indianapolis, IN, USA). This does not alter the authors' adherence to all PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. CONSORT diagram.
ARDS, acute respiratory distress syndrome; SCT, stem cell transplantation; plts, platelet count.
Figure 2
Figure 2. Probability of being alive and off the ventilator until day 28 in study groups.
Figure 3
Figure 3. Probability of survival until day 28 in study groups.
Figure 4
Figure 4. Probability of survival until day 90 in study groups.
See this image and copyright information in PMC

References

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