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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Acute Aortic Dissection

Intervention / Treatment
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* Drug: Sivelestat sodium was given intravenously
* Drug: Placebo was given intravenously


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-75; Spontaneous acute (≤14 days) type A aortic dissection; In the emergency department, hypothermic circulatory arrest combined with unilateral anterograde cerebral perfusion was expected to be performed on the aortic arch surgery; Preoperative PaO2/FiO2≤200mmHg; Exclusion Criteria: Preoperative cardiogenic shock; preoperative liver insufficiency; Preoperative dissection involves important organs and seriously endangers the patient's life Pregnant women; hereditary connective tissue diseases, such as Marfan syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome, etc.; Behcet's disease; aortitis; There is a history of neurologic disease that has been clearly diagnosed; There is a history of a clearly diagnosed mental illness; There is a definite diagnosis of chronic respiratory disease; There is a clearly diagnosed immune disease; There is a definite diagnosis of hematological diseases; severe renal failure or require dialysis treatment; Taking anti-inflammatory or anti-coagulant drugs within a week before admission; People who are allergic to sivelestat sodium and other ingredients; Has participated in other clinical trials; The clinician judges that it is not suitable for inclusion in the study;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sivelestat sodium group<br>sivelestat sodium | Drug: Sivelestat sodium was given intravenously<br>* 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.<br>* Other names: Sivelestat sodium group;|
| Placebo Comparator: Placebo control group<br>Placebo control | Drug: Placebo was given intravenously<br>* 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.<br>* Other names: Placebo control group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total invasive mechanical ventilation | mode and duration | 28 days after surgery | 
| Total non-invasive mechanical ventilation | mode and duration | 28 days after surgery | 
| Total high flow oxygen uptake | mode and duration | 28 days after surgery | 
| Oxygenation index and area under curve | Oxygenation index | 28 days after surgery | 
| PaO2/FiO2≤300mmHg Duration | Duration of hypoxemia | 28 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute type A aortic dissection, preoperative moderate to severe hypoxemia, sivelestat sodium