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

• Published in: PloS one 2014-03, Vol.9 (3), p.e90983
• Main Authors: Cornet, Alexander D, Groeneveld, A B Johan, Hofstra, Jorrit J, Vlaar, Alexander P, Tuinman, Pieter R, van Lingen, Arthur, Levi, Marcel, Girbes, Armand R J, Schultz, Marcus J, Beishuizen, Albertus
• Format: Article
• Language: English
• Subjects: Activated protein C; Adult respiratory distress syndrome; Aged; Bleeding; Clinical trials; Drug therapy; Female; Hospitals; Humans; Inflammation; Intensive care units; Intravenous administration; Lungs; Male; Mechanical ventilation; Medicine and Health Sciences; Middle Aged; Mortality; Patients; Permeability; Protein C; Protein C - therapeutic use; Randomization; Recombinant Proteins - therapeutic use; Research and Analysis Methods; Respiratory distress syndrome; Respiratory Distress Syndrome, Adult - drug therapy; Transferrin; Transferrins; Ventilation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0090983

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 The study was prematurely discontinued because rh-APC was withdrawn from the market.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.