TY - JOUR
T1 - Thrombomodulin Alfa for acute exacerbation of idiopathic pulmonary fibrosis
T2 - A randomized, double-blind placebo-controlled trial
AU - Kondoh, Yasuhiro
AU - Azuma, Arata
AU - Inoue, Yoshikazu
AU - Ogura, Takashi
AU - Sakamoto, Susumu
AU - Tsushima, Kenji
AU - Johkoh, Takeshi
AU - Fujimoto, Kiminori
AU - Ichikado, Kazuya
AU - Matsuzawa, Yasuo
AU - Saito, Takefumi
AU - Kishi, Kazuma
AU - Tomii, Keisuke
AU - Sakamoto, Noriho
AU - Aoshima, Masahiro
AU - Araya, Jun
AU - Izumi, Shinyu
AU - Arita, Machiko
AU - Abe, Mitsuhiro
AU - Yamauchi, Hiroyoshi
AU - Shindoh, Joe
AU - Suda, Takafumi
AU - Okamoto, Masaki
AU - Ebina, Masahito
AU - Yamada, Yoshihito
AU - Tohda, Yuji
AU - Kawamura, Tetsuji
AU - Taguchi, Yoshio
AU - Ishii, Hiroshi
AU - Hashimoto, Naozumi
AU - Abe, Shinji
AU - Taniguchi, Hiroyuki
AU - Tagawa, Jun
AU - Bessho, Koji
AU - Yamamori, Natsuki
AU - Homma, Sakae
N1 - Publisher Copyright:
Copyright © 2020 by the American Thoracic Society
PY - 2020
Y1 - 2020
N2 - Rationale: Acute exacerbation during the course of idiopathic pulmonary fibrosis causes a poor prognosis. Coagulation abnormalities and endothelial damage are involved in its pathogenesis. Thrombomodulin alfa, a recombinant human soluble thrombomodulin, has anticoagulant and antiinflammatory effects. Several clinical studies have shown that thrombomodulin alfa may improve survival of acute exacerbation. Objectives: To determine the efficacy and safety of thrombomodulin alfa compared with placebo in acute exacerbation of idiopathic pulmonary fibrosis. Methods: This randomized, double-blind placebo-controlled phase 3 study conducted at 27 sites in Japan involved patients with an acute exacerbation of idiopathic pulmonary fibrosis. Subjects were randomized 1:1 to receive placebo or thrombomodulin alfa (380 U/kg/d for 14 d by intravenous drip infusion). All subjects were treated with high-dose corticosteroid therapy. The primary endpoint was the survival proportion on Day 90. Measurements and Main Results: Of the 82 randomized subjects, 77 completed the study and were included in the full analysis set (thrombomodulin alfa, n = 40; placebo, n = 37). The survival proportions on Day 90 were 72.5% (29 of 40) in the thrombomodulin alfa group and 89.2% (33 of 37) in the placebo group, a difference of 216.7 percentage points (95% confidence interval, 233.8 to 0.4%; P = 0.0863). In the safety population (n = 80), bleeding adverse events occurred in the thrombomodulin alfa group (10 of 42; 23.8%) and the placebo group (4 of 38; 10.5%). Conclusions: Thrombomodulin alfa did not improve the 90-day survival proportion. The present results suggest that the use of thrombomodulin alfa for the treatment of acute exacerbation of idiopathic pulmonary fibrosis not be recommended.
AB - Rationale: Acute exacerbation during the course of idiopathic pulmonary fibrosis causes a poor prognosis. Coagulation abnormalities and endothelial damage are involved in its pathogenesis. Thrombomodulin alfa, a recombinant human soluble thrombomodulin, has anticoagulant and antiinflammatory effects. Several clinical studies have shown that thrombomodulin alfa may improve survival of acute exacerbation. Objectives: To determine the efficacy and safety of thrombomodulin alfa compared with placebo in acute exacerbation of idiopathic pulmonary fibrosis. Methods: This randomized, double-blind placebo-controlled phase 3 study conducted at 27 sites in Japan involved patients with an acute exacerbation of idiopathic pulmonary fibrosis. Subjects were randomized 1:1 to receive placebo or thrombomodulin alfa (380 U/kg/d for 14 d by intravenous drip infusion). All subjects were treated with high-dose corticosteroid therapy. The primary endpoint was the survival proportion on Day 90. Measurements and Main Results: Of the 82 randomized subjects, 77 completed the study and were included in the full analysis set (thrombomodulin alfa, n = 40; placebo, n = 37). The survival proportions on Day 90 were 72.5% (29 of 40) in the thrombomodulin alfa group and 89.2% (33 of 37) in the placebo group, a difference of 216.7 percentage points (95% confidence interval, 233.8 to 0.4%; P = 0.0863). In the safety population (n = 80), bleeding adverse events occurred in the thrombomodulin alfa group (10 of 42; 23.8%) and the placebo group (4 of 38; 10.5%). Conclusions: Thrombomodulin alfa did not improve the 90-day survival proportion. The present results suggest that the use of thrombomodulin alfa for the treatment of acute exacerbation of idiopathic pulmonary fibrosis not be recommended.
KW - Acute exacerbation
KW - Anticoagulants
KW - Clinical trial
KW - Idiopathic pulmonary fibrosis
KW - Thrombomodulin
UR - http://www.scopus.com/inward/record.url?scp=85081942422&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081942422&partnerID=8YFLogxK
U2 - 10.1164/RCCM.201909-1818OC
DO - 10.1164/RCCM.201909-1818OC
M3 - Article
C2 - 31917621
AN - SCOPUS:85081942422
SN - 1073-449X
VL - 201
SP - 1110
EP - 1119
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 9
ER -