TY - JOUR
T1 - Recombinant human activated protein C in the treatment of acute respiratory distress syndrome: a randomized clinical trial
AU - Cornet, Alexander D.
AU - Groeneveld, A. B. Johan
AU - Hofstra, Jorrit J.
AU - Vlaar, Alexander P.
AU - Tuinman, Pieter R.
AU - van Lingen, Arthur
AU - Levi, Marcel
AU - Girbes, Armand R. J.
AU - Schultz, Marcus J.
AU - Beishuizen, Albertus
PY - 2014
Y1 - 2014
N2 - 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. 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. A 4-day course of intravenous rh-APC (24 mcg/kg/h) (n = 33) versus saline (n = 38). 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. 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 The study was prematurely discontinued because rh-APC was withdrawn from the market. 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. Nederlands Trial Register ISRCTN 52566874
AB - 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. 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. A 4-day course of intravenous rh-APC (24 mcg/kg/h) (n = 33) versus saline (n = 38). 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. 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. 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. Nederlands Trial Register ISRCTN 52566874
U2 - https://doi.org/10.1371/journal.pone.0090983
DO - https://doi.org/10.1371/journal.pone.0090983
M3 - Article
C2 - 24632673
SN - 1932-6203
VL - 9
SP - e90983
JO - PLoS ONE
JF - PLoS ONE
IS - 3
M1 - e90983
ER -