An open-label, randomized, phase 3 study of the efficacy and safety of antithrombin gamma in patients with sepsis-induced disseminated intravascular coagulation syndrome

Shigeatsu Endo, Ryutaro Shimazaki, Satoshi Gando, Shigeto Oda, Yasuhiro Ootomo, Masanao Miura, Shinji Ogura, Yutaka Eguchi, Joji Kotani, Norio Yamashita, Hiroyasu Ishikura, Yuichiro Sakamoto, Takeshi Takahashi, Yasushi Suzuki, Shigeki Kushimoto, Nobuya Kitamura, Naoyuki Matsuda, Takahiro Fujita, Mitsuhide Kitano, Junko YamaguchiYoshikazu Yasuda, Hayato Takayama, Toshiharu Tanaka, Tetsuya Matsuoka, Tetsuhiro Takei, Tsuyoshi Hatada, Masahiro Tamashiro, Satoshi Fujimi, Osamu Nishida, Kazuhito Tamehiro, Junichi Maehara, Shinsuke Fujiwara, Hideo Wada

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: A recombinant form of antithrombin (AT), called AT gamma, is being developed as an alternative to AT derived from human plasma. To compare the efficacy and safety of AT gamma to plasma-derived AT (pAT), we conducted a randomized, open-label, multicenter trial in patients with sepsis-induced disseminated intravascular coagulation (DIC). Methods: Eligible patients, recruited at 30 clinical sites, had been diagnosed with sepsis-induced DIC (by the Japanese Association for Acute Medicine [JAAM] DIC criteria) and AT activity at 70% or below. Patients were randomized 1:1 to either 36 IU/kg/day AT gamma (n = 110) or 30 IU/kg/day pAT (n = 112), both administered intravenously for 5 days. The primary endpoint was recovery from DIC at day 6 or early study withdrawal. DIC recovery was defined as a DIC score of less than four. Secondary endpoints were DIC score, outcome on day 28, sequential organ failure assessment score, acute physiology and chronic health evaluation II score (APACHE II), and plasma AT activity. Adverse events and adverse drug reactions were recorded using MedDRA/J version 16.0. Results: Baseline patient demographics and clinical features were similar in the two treatment groups. On day 6 (or at withdrawal), DIC recovery had occurred in 62 of 110 (56.4%; 95% confidence interval, 46.6-65.8%) patients in the AT gamma group and 59 of 112 (52.7%; 95% confidence interval, 43.0-62.2%) patients in the pAT group. In both treatment groups, DIC recovery rate values tended to be higher when stratified by baseline AT activity rates. All changes in other secondary endpoints were similar in both treatment groups. Safety was also similar in the two treatment groups. Adverse events occurred in 89 of 108 (82.4%) patients in the AT gamma group and 99 of 113 (87.6%) patients in the pAT group. Conclusions: Safety and efficacy were similar for 36 IU/kg/day AT gamma and 30 IU/kg/day pAT. These results confirm that AT gamma is an excellent alternative to pAT for improving outcomes for patients with DIC. Trial registration: ClinicalTrials.gov identifier: NCT01384903; June 2011.

Original languageEnglish
Article number75
JournalJournal of Intensive Care
Volume6
Issue number1
DOIs
Publication statusPublished - 16-11-2018

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

Fingerprint Dive into the research topics of 'An open-label, randomized, phase 3 study of the efficacy and safety of antithrombin gamma in patients with sepsis-induced disseminated intravascular coagulation syndrome'. Together they form a unique fingerprint.

  • Cite this

    Endo, S., Shimazaki, R., Gando, S., Oda, S., Ootomo, Y., Miura, M., Ogura, S., Eguchi, Y., Kotani, J., Yamashita, N., Ishikura, H., Sakamoto, Y., Takahashi, T., Suzuki, Y., Kushimoto, S., Kitamura, N., Matsuda, N., Fujita, T., Kitano, M., ... Wada, H. (2018). An open-label, randomized, phase 3 study of the efficacy and safety of antithrombin gamma in patients with sepsis-induced disseminated intravascular coagulation syndrome. Journal of Intensive Care, 6(1), [75]. https://doi.org/10.1186/s40560-018-0339-z