A Pilot Study of Sivelestat Sodium to Shorten Mechanical Ventilation in Acute Aortic Dissection

Summary

This is A prospective, randomized, placebo-controlled, reestimable adaptive clinical study to evaluate the efficacy and safety of perioperative application of sivelestat sodium to shorten the duration of postoperative invasive mechanical ventilation in acute type A aortic dissection patients with preoperative moderate and severe hypoxemia (PaO2/FiO2≤200mmHg).

Timeline

Start

2023-05

Primary completion

2023-12

Completion

2024-02

Publications

• Results Bossone E, Eagle KA. Epidemiology and management of aortic disease: aortic aneurysms and acute aortic syndromes. Nat Rev Cardiol. 2021 May;18(5):331-348. doi: 10.1038/s41569-020-00472-6. Epub 2020 Dec 22.
• Results Guo Z, Yang Y, Zhao M, Zhang B, Lu J, Jin M, Cheng W. Preoperative hypoxemia in patients with type A acute aortic dissection: a retrospective study on incidence, related factors and clinical significance. J Thorac Dis. 2019 Dec;11(12):5390-5397. doi: 10.21037/jtd.2019.11.68.
• Results Liu N, Zhang W, Ma W, Shang W, Zheng J, Sun L. Risk factors for hypoxemia following surgical repair of acute type A aortic dissection. Interact Cardiovasc Thorac Surg. 2017 Feb 1;24(2):251-256. doi: 10.1093/icvts/ivw272.
• Results Wang Y, Xue S, Zhu H. Risk factors for postoperative hypoxemia in patients undergoing Stanford A aortic dissection surgery. J Cardiothorac Surg. 2013 Apr 30;8:118. doi: 10.1186/1749-8090-8-118.
• Results Thompson BT, Chambers RC, Liu KD. Acute Respiratory Distress Syndrome. N Engl J Med. 2017 Aug 10;377(6):562-572. doi: 10.1056/NEJMra1608077. No abstract available.
• Results Duan XZ, Xu ZY, Lu FL, Han L, Tang YF, Tang H, Liu Y. Inflammation is related to preoperative hypoxemia in patients with acute Stanford type A aortic dissection. J Thorac Dis. 2018 Mar;10(3):1628-1634. doi: 10.21037/jtd.2018.03.48.
• Results Oda S, Aibiki M, Ikeda T, Imaizumi H, Endo S, Ochiai R, Kotani J, Shime N, Nishida O, Noguchi T, Matsuda N, Hirasawa H; Sepsis Registry Committee of The Japanese Society of Intensive Care Medicine. The Japanese guidelines for the management of sepsis. J Intensive Care. 2014 Oct 28;2(1):55. doi: 10.1186/s40560-014-0055-2. eCollection 2014.
• Results Hashimoto S, Okayama Y, Shime N, Kimura A, Funakoshi Y, Kawabata K, Ishizaka A, Amaya F. Neutrophil elastase activity in acute lung injury and respiratory distress syndrome. Respirology. 2008 Jun;13(4):581-4. doi: 10.1111/j.1440-1843.2008.01283.x. Epub 2008 Apr 10.
• Results Polverino E, Rosales-Mayor E, Dale GE, Dembowsky K, Torres A. The Role of Neutrophil Elastase Inhibitors in Lung Diseases. Chest. 2017 Aug;152(2):249-262. doi: 10.1016/j.chest.2017.03.056. Epub 2017 Apr 23.
• Results Kotani M, Kotani T, Ishizaka A, Fujishima S, Koh H, Tasaka S, Sawafuji M, Ikeda E, Moriyama K, Kotake Y, Morisaki H, Aikawa N, Ohashi A, Matsushima K, Huang YC, Takeda J. Neutrophil depletion attenuates interleukin-8 production in mild-overstretch ventilated normal rabbit lung. Crit Care Med. 2004 Feb;32(2):514-9. doi: 10.1097/01.CCM.0000110677.16968.E4.
• Results Miyoshi S, Hamada H, Ito R, Katayama H, Irifune K, Suwaki T, Nakanishi N, Kanematsu T, Dote K, Aibiki M, Okura T, Higaki J. Usefulness of a selective neutrophil elastase inhibitor, sivelestat, in acute lung injury patients with sepsis. Drug Des Devel Ther. 2013 Apr 10;7:305-16. doi: 10.2147/DDDT.S42004. Print 2013.
• Results Morimoto K, Nishimura K, Miyasaka S, Maeta H, Taniguchi I. The effect of sivelestat sodium hydrate on severe respiratory failure after thoracic aortic surgery with deep hypothermia. Ann Thorac Cardiovasc Surg. 2011;17(4):369-75. doi: 10.5761/atcs.oa.10.01555.
• Results Morimoto N, Morimoto K, Morimoto Y, Takahashi H, Asano M, Matsumori M, Okada K, Okita Y. Sivelestat attenuates postoperative pulmonary dysfunction after total arch replacement under deep hypothermia. Eur J Cardiothorac Surg. 2008 Oct;34(4):798-804. doi: 10.1016/j.ejcts.2008.07.010. Epub 2008 Aug 22.
• Results Ryugo M, Sawa Y, Takano H, Matsumiya G, Iwai S, Ono M, Hata H, Yamauchi T, Nishimura M, Fujino Y, Matsuda H. Effect of a polymorphonuclear elastase inhibitor (sivelestat sodium) on acute lung injury after cardiopulmonary bypass: findings of a double-blind randomized study. Surg Today. 2006;36(4):321-6. doi: 10.1007/s00595-005-3160-y.
• Results Niino T, Hata M, Sezai A, Yoshitake I, Unosawa S, Fujita K, Shimura K, Osaka S, Minami K. Efficacy of neutrophil elastase inhibitor on type A acute aortic dissection. Thorac Cardiovasc Surg. 2010 Apr;58(3):164-8. doi: 10.1055/s-0029-1240846. Epub 2010 Apr 7.
• Results Toyama S, Hatori F, Shimizu A, Takagi T. A neutrophil elastase inhibitor, sivelestat, improved respiratory and cardiac function in pediatric cardiovascular surgery with cardiopulmonary bypass. J Anesth. 2008;22(4):341-6. doi: 10.1007/s00540-008-0645-z. Epub 2008 Nov 15.
• Results Nomura N, Asano M, Saito T, Nakayama T, Mishima A. Sivelestat attenuates lung injury in surgery for congenital heart disease with pulmonary hypertension. Ann Thorac Surg. 2013 Dec;96(6):2184-91. doi: 10.1016/j.athoracsur.2013.07.017. Epub 2013 Sep 25.
• Results Inoue N, Oka N, Kitamura T, Shibata K, Itatani K, Tomoyasu T, Miyaji K. Neutrophil elastase inhibitor sivelestat attenuates perioperative inflammatory response in pediatric heart surgery with cardiopulmonary bypass. Int Heart J. 2013;54(3):149-53. doi: 10.1536/ihj.54.149.
• Results Kohira S, Oka N, Inoue N, Itatani K, Hanayama N, Kitamura T, Fujii M, Takeda A, Oshima H, Tojo K, Yoshitake S, Miyaji K. Effect of the neutrophil elastase inhibitor sivelestat on perioperative inflammatory response after pediatric heart surgery with cardiopulmonary bypass: a prospective randomized study. Artif Organs. 2013 Dec;37(12):1027-33. doi: 10.1111/aor.12103. Epub 2013 Jul 3.
• Results Kohira S, Oka N, Inoue N, Itatani K, Kitamura T, Horai T, Oshima H, Tojo K, Yoshitake S, Miyaji K. Effect of additional preoperative administration of the neutrophil elastase inhibitor sivelestat on perioperative inflammatory response after pediatric heart surgery with cardiopulmonary bypass. Artif Organs. 2014 Dec;38(12):1018-23. doi: 10.1111/aor.12311. Epub 2014 Apr 21.
• Results Fujii M, Miyagi Y, Bessho R, Nitta T, Ochi M, Shimizu K. Effect of a neutrophil elastase inhibitor on acute lung injury after cardiopulmonary bypass. Interact Cardiovasc Thorac Surg. 2010 Jun;10(6):859-62. doi: 10.1510/icvts.2009.225243. Epub 2010 Mar 30.
• Results Abe T, Usui A, Oshima H, Akita T, Ueda Y. A pilot randomized study of the neutrophil elastase inhibitor, Sivelestat, in patients undergoing cardiac surgery. Interact Cardiovasc Thorac Surg. 2009 Aug;9(2):236-40. doi: 10.1510/icvts.2009.206193. Epub 2009 May 15.
• Results Yamashiro S, Arakaki R, Kise Y, Kuniyoshi Y. Prevention of Pulmonary Edema after Minimally Invasive Cardiac Surgery with Mini-Thoracotomy Using Neutrophil Elastase Inhibitor. Ann Thorac Cardiovasc Surg. 2018 Feb 20;24(1):32-39. doi: 10.5761/atcs.oa.17-00102. Epub 2017 Nov 8.
• Results Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, Hrobjartsson A, Mann H, Dickersin K, Berlin JA, Dore CJ, Parulekar WR, Summerskill WS, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013 Feb 5;158(3):200-7. doi: 10.7326/0003-4819-158-3-201302050-00583.

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Indications