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

Acute Aortic Dissection Clinical Trial

Official title:

A Pilot Study of Perioperative Application of Sivelestat Sodium in Acute Type A Aortic Dissection Patients With Preoperative Moderate to Severe Hypoxemia to Shorten the Duration of Postoperative Invasive Mechanical Ventilation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05874700
• Other study ID #: 2023-4
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 2023
• Est. completion date: February 2024

Study information

• Verified date: May 2023
• Source: Beijing Anzhen Hospital
• Contact: Xiaotong Hou, MD
• Phone: 8610 64456631
• Email: xt.hou[@]ccmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

In recent years, sivelestat sodium therapy has been used to treat and prevent CPB-associated lung injury with good results. Morimoto K et al., randomized control of a small sample size, demonstrated that sivelestat sodium improves respiratory function in patients with severe respiratory failure after hypothermia thoracic aortic surgery. A retrospective study by Morimoto N et al. confirmed that prophylactic application of sivelestat sodium at the beginning of CPB could improve postoperative respiratory function and shorten the duration of mechanical ventilation in patients with hypothermic circulatory arrest. At present, there is a lack of reliable RCTS to confirm that the intraoperative application of sivelestat sodium can effectively treat preoperative acute lung injury, improve CPB-related lung injury, and reduce the incidence of postoperative acute lung injury. Therefore, the objective of this study was to design A randomized controlled study to evaluate the clinical efficacy and safety of intraoperative use of sivelestat sodium to shorten the duration of postoperative invasive mechanical ventilation in acute type A aortic dissection patients with preoperative moderate to severe hypoxemia. The purpose of this preliminary clinical trial is to provide theoretical basis for sample size calculation of randomized controlled trials, and to evaluate the scientific nature and feasibility of randomized controlled trials.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: February 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Aged 18-75;

2. Spontaneous acute (=14 days) type A aortic dissection;

3. In the emergency department, hypothermic circulatory arrest combined with unilateral anterograde cerebral perfusion was expected to be performed on the aortic arch surgery;

4. Preoperative PaO2/FiO2=200mmHg;

Exclusion Criteria:

1. Preoperative cardiogenic shock;

2. preoperative liver insufficiency;

3. Preoperative dissection involves important organs and seriously endangers the patient's life

4. Pregnant women;

5. hereditary connective tissue diseases, such as Marfan syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome, etc.;

6. Behcet's disease;

7. aortitis;

8. There is a history of neurologic disease that has been clearly diagnosed;

9. There is a history of a clearly diagnosed mental illness;

10. There is a definite diagnosis of chronic respiratory disease;

11. There is a clearly diagnosed immune disease;

12. There is a definite diagnosis of hematological diseases;

13. severe renal failure or require dialysis treatment;

14. Taking anti-inflammatory or anti-coagulant drugs within a week before admission;

15. People who are allergic to sivelestat sodium and other ingredients;

16. Has participated in other clinical trials;

17. The clinician judges that it is not suitable for inclusion in the study;

Related Conditions & MeSH terms

• Acute Aortic Dissection
• Aortic Dissection

Intervention

Drug:
• Sivelestat sodium was given intravenously
Anesthesia induction began with a 0.2mg/Kg/h pump test drug until 48 hours after endotracheal intubation was removed or up to 7 days. If the patient was judged to have successfully removed the endotracheal tube, drug administration was discontinued; If the endotracheal intubation was not removed successfully up to 7 days, drug administration was also discontinued. During CPB, 0.1mg/100mL of the experimental drug was injected into the circulating pump immediately after CPB began.
• Placebo was given intravenously
Anesthesia induction began with a 0.2mg/Kg/h pump test drug until 48 hours after endotracheal intubation was removed or up to 7 days. If the patient was judged to have successfully removed the endotracheal tube, drug administration was discontinued; If the endotracheal intubation was not removed successfully up to 7 days, drug administration was also discontinued. During CPB, 0.1mg/100mL of the experimental drug was injected into the circulating pump immediately after CPB began.

Locations

Country	Name	City	State
China	Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Xiaotong Hou

Country where clinical trial is conducted

China, 

References & Publications (24)

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 M — View Citation

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. — View Citation

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 s — View Citation

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. — View Citation

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. — View Citation

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: 10.2 — View Citation

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 20 — View Citation

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 — View Citation

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 cardi — View Citation

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 hear — View Citation

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 ventila — View Citation

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. — View Citation

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 — View Citation

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.10.01 — View Citation

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: 1 — View Citation

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 — View Citation

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. — View Citation

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 I — View Citation

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. — View Citation

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 — View Citation

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. — View Citation

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. Ep — View Citation

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. — View Citation

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.17-001 — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Invasive mechanical ventilation time	Duration from the initiation of invasive mechanical ventilation to the first successful removal of the endotracheal tube	28 days after surgery
Secondary	Total invasive mechanical ventilation	mode and duration	28 days after surgery
Secondary	Total non-invasive mechanical ventilation	mode and duration	28 days after surgery
Secondary	Total high flow oxygen uptake	mode and duration	28 days after surgery
Secondary	Oxygenation index and area under curve	Oxygenation index	28 days after surgery
Secondary	PaO2/FiO2=300mmHg Duration	Duration of hypoxemia	28 days after surgery