Type A Aortic Dissection, Organ Failure, Multiple
Conditions
Keywords
Type A Aortic Dissection, SOFA, Sivelestat Sodium, Multiple Organ Failure
Brief summary
The goal of this multicenter, double-blind, randomized controlled trial is to learn if sivelestat sodium (Siv) can protect the organ function in patients suffered operation for acute type A aortic dissection. The main questions it aims to answer are: * Can the 3-day-treatment of Siv enlarge the Day-0-to-Day-5 drop in the organ-health score (SOFA score)? * Can this treatment significantly shrink the area under the SOFA curve from first dose to Day 5? * Can this treatment significantly improve the end of patients in 28 days (clinical outcomes)? Researchers will compare drug Siv to a placebo (a look-alike substance that contains no drug) to see if drug Siv works. Participants will: * Take drug Siv or the placebo through vein continuously for 72 hours * Receiving regular intensive care in ICU after the operation
Interventions
PROCEDUREConventional treatment
Beside the using of Sivelestat Sodium or placebo, all postoperative care will adhere to each center's standard protocols for type A aortic dissection.
The daily dose (4.8 mg/kg) is diluted in 48 mL of 0.9 % saline and administered as a continuous intravenous infusion over 24 hours at 2 mL/h (equivalent to 0.2 mg/kg/h) for 72 consecutive hours.
DRUGPlacebo
An equal volume of placebo-containing only the excipients of sivelestat sodium and diluted to 48 mL with 0.9 % saline-will be infused at 2 mL/h for 72 consecutive hours.
Sponsors
The First Affiliated Hospital of Anhui Medical University
Fujian Provincial Hospital
The University of Hong Kong-Shenzhen Hospital
First Affiliated Hospital Xi'an Jiaotong University
Guangdong Provincial People's Hospital
Changhai Hospital
Shanghai Zhongshan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
a Multicenter, Double-blind RCT
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 years inclusive. 2. Written informed consent obtained before participation. 3. Confirmed acute Stanford type A aortic dissection scheduled for surgical repair.
Exclusion criteria
1. Life expectancy ≤ 48 hours. 2. Pregnant or lactation. 3. Severe pre-operative liver dysfunction: Child-Turcotte-Pugh score 10-15. 4. Severe pre-operative renal dysfunction: acute or chronic kidney injury meeting criteria for renal-replacement therapy. 5. Confirmed COPD or asthma. 6. Immunosuppression: long-term or \> 2 weeks continuous systemic corticosteroids. 7. Concomitant or anticipated use of immunomodulators (Xue-Bi-Jing injection, thymosin, IVIG). 8. Medical or psychological condition that would interfere with study participation, assessment, or outcomes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ΔSOFA5 | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the first dose) | ΔSOFA5 is defined as the decrease level of SOFA(Sequential Organ Failure Assessment) score from baseline to the fifth day. SOFA score ranges from 0\ 24, the higher the score, the poorer the functionality of multiple organs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC - SOFA | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the first dose) | Area under the SOFA-time curve |
| Clinical Outcomes - Incidence of tracheotomy | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | Incidence of tracheotomy |
| Clinical Outcomes - Re-intubation rate | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | Re-intubation rate |
| Clinical Outcomes - Gastrointestinal bleeding （count, rate） | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | Gastrointestinal bleeding （count, rate） |
| Clinical Outcomes - Infection | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | Infection: Serious infections such as bloodstream infections, sepsis, ventilator-associated pneumonia |
| Clinical Outcomes - In-hospital mortality | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | In-hospital mortality |
| Clinical Outcomes - ICU length of stay (days) | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | ICU length of stay (days) |
| Clinical Outcomes - Total hospital length of stay (days) | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | Total hospital length of stay (days) |
| Clinical Outcomes - Ventilator-free days at day 28 (days) | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | Mechanical ventilation includes: invasive mechanical ventilation and non-invasive mechanical ventilation |
| Clinical Outcomes - Invasive ventilatory support duration at day 28 (days) | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | Invasive ventilatory support: invasive mechanical ventilation |
| Clinical Outcomes - Respiratory-support-free time at day 28 (days) | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | Respiratory support includes: invasive mechanical ventilation, non-invasive mechanical ventilation, and high-flow oxygen |
| Clinical Outcomes - Organ-support-free days at day 28(days) | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | days free of mechanical ventilation, vasopressors, and renal-replacement therapy |
| Clinical Outcomes - Central nervous system complications during ICU stay | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | Central nervous system complications during ICU stay: cerebral infarction, intracranial hemorrhage, hypoxic-ischemic encephalopathy |
| Clinical Outcomes - Delirium incidence during ICU stay | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | Delirium incidence during ICU stay |
| Clinical Outcomes - Incidence of acute kidney injury (AKI) | from the entry of ICU(baseline, post-operatively) to the 28th day after surgery | Incidence of acute kidney injury (AKI) |
| Laboratory Test Results - Arterial blood gas: pH | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | pH result from arterial blood gas |
| Laboratory Test Results - Arterial blood gas: PaO₂/FiO₂ | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | PaO₂/FiO₂ result from arterial blood gas |
| Laboratory Test Results - Arterial blood gas: SpO₂/FiO₂ | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | SpO₂/FiO₂ result from arterial blood gas |
| Laboratory Test Results - Arterial blood gas: PaO₂ | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | PaO₂ result from arterial blood gas |
| Laboratory Test Results - Arterial blood gas: PaCO₂ | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | PaCO₂ result from arterial blood gas |
| Laboratory Test Results - Arterial blood gas: SpO₂ | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | SpO₂ result from arterial blood gas |
| Laboratory Test Results - Arterial blood gas: lactate | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | lactate result from arterial blood gas |
| Laboratory Test Results - Liver & kidney function: AST | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | AST from Liver & kidney function |
| Laboratory Test Results - Liver & kidney function: ALT | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | ALT from Liver & kidney function |
| Laboratory Test Results - Liver & kidney function: ALP | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | ALP from Liver & kidney function |
| Laboratory Test Results - Liver & kidney function: GGT | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | GGT from Liver & kidney function |
| Laboratory Test Results - Liver & kidney function: TBil | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | TBil from Liver & kidney function |
| Laboratory Test Results - Liver & kidney function: DBIL | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | DBIL from Liver & kidney function |
| Laboratory Test Results - Liver & kidney function: ALB | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | ALB from Liver & kidney function |
| Laboratory Test Results - Liver & kidney function: Scr | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | Scr from Liver & kidney function |
| Laboratory Test Results - Liver & kidney function: BUN | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | BUN from Liver & kidney function |
| Laboratory Test Results - Liver & kidney function: eGFR | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | eGFR from Liver & kidney function |
| Laboratory Test Results - Liver & kidney function: NGAL | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | NGAL from Liver & kidney function |
| Laboratory Test Results - Myocardial injury: CK-MB | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | CK-MB from Myocardial injury |
| Laboratory Test Results - Myocardial injury: LDH | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | LDH from Myocardial injury |
| Laboratory Test Results - Myocardial injury: cTnI or cTnT | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | cTnI or cTnT from Myocardial injury |
| Laboratory Test Results - Myocardial injury: BNP or NT-proBNP | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | BNP or NT-proBNP from Myocardial injury |
| Laboratory Test Results - Brain injury: NSE | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | NSE result from blood test, Brain injury part |
| Laboratory Test Results - Inflammation: CRP | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | CRP result from Inflammation test |
| Laboratory Test Results - Inflammation: IL-6 | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | IL-6 result from Inflammation test8 |
| Laboratory Test Results - Inflammation: IL-8 | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | IL-8 result from Inflammation test |
| Laboratory Test Results - Inflammation: IL-10 | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | IL-10 result from Inflammation test |
| Laboratory Test Results - Inflammation: TNF-α | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | TNF-α result from Inflammation test |
| Laboratory Test Results - Inflammation: PCT | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the start of treatment) | PCT result from Inflammation test |
Other
| Measure | Time frame | Description |
|---|---|---|
| Plasma neutrophil elastase levels (exploratory outcome) | from the entry of ICU(baseline, post-operatively) to the fifth day in ICU(the fifth day after the first dose) | Plasma concentration of neutrophil elastase at 1day, 3day and 5day after the first dose in 40 participants enrolled at the main center (20 per arm). |
Countries
China
Contacts
Primary ContactGuowei Tu
Backup ContactChenxu Lin
Outcome results
None listed