Ignite Creation Date:
2025-12-25 @ 3:45 AM
Ignite Modification Date:
2025-12-26 @ 2:31 AM
Study NCT ID:
NCT05534802
Status:
COMPLETED
Last Update Posted:
2025-01-20
First Post:
2022-08-31
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Ulinastatin Improves and Prevents Cardiac Dysfunction Induced by Cardiopulmonary Bypass
Sponsor:
Qin Zhang
Organization:
Study Overview
Official Title:
Ulinastatin Improves and Prevents Cardiac Dysfunction Induced by Cardiopulmonary Bypass by Reducing Cardiac Endothelial Permeability
Status:
COMPLETED
Status Verified Date:
2025-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This project explores the role and mechanism of ulinastatin in preventing cardiac dysfunction caused by cardiopulmonary bypass by reducing cardiac endothelial permeability through clinical research. Our previous basic research has found that inhibiting the TK/B1R/ARNT/MMP3/iNOS signaling axis in the acute phase of cardiac R/I can reduce the permeability of cardiac endothelial cells, reduce cardiac edema and improve cardiac function (this part has been completed) . This study intends to investigate the effects of ulinastatin on 24-hour cardiac function and prognosis in patients undergoing cardiac surgery undergoing cardiopulmonary bypass (cardiac function, inflammatory indicators, coagulation function, capillary leakage indicators, 28-day survival time, CCU time). At the same time, we observed the dynamic changes of TK/B1R/MMP3 during cardiopulmonary bypass in patients undergoing cardiac surgery and explored its relationship with prognosis, as well as the effect of ulinastatin intervention on TK/B1R/MMP3 before and after cardiopulmonary bypass.
Detailed Description:
1. Baseline Period Visit 1 (within 24 hours before surgery)
* Sign informed consent
* Check inclusion/exclusion criteria
* Demographic data (sex, age, occupation, etc.)
* Past medical history (stroke, hypertension, diabetes, dyslipidemia, coronary heart disease, diabetes, etc.) and medication history in the past 3 months
* Vital signs (temperature, pulse, respiration, blood pressure)
* Preoperative ECG
* Preoperative echocardiography
* Laboratory tests (blood routine, blood glucose, blood lipids, liver and kidney function, myocardial enzymes, blood electrolytes, coagulation function)
* Concomitant therapy
* Adverse events
2. Intraoperative cardiopulmonary bypass
* Record vital signs and various physiological indicators in the operating room.
* Routinely perform central venous puncture to establish venous access and monitor central venous pressure, and radial artery puncture to monitor invasive arterial pressure.
* After general anesthesia and endotracheal intubation, routine blood chemistry and arterial blood gas analysis were performed.
* After collecting the above blood samples for testing, the remaining blood was centrifuged, and the plasma was frozen at -80°C for subsequent testing (levels of CRP, IL-6, IL-10, TNF-α, TK/B1R/MMP3, etc.).
* Conventional treatment group: On the basis of general anesthesia, the extracorporeal circulation circuit was routinely prefilled. Management of CPB includes blood gas acid-base electrolyte management, anticoagulation management, invasive arterial blood pressure monitoring, MAP in the range of 50-80 mmHg, hematocrit maintained at 20-25%, and non-pulsatile flow rate of 2.0-2.4 L/min/ m2. During cardiopulmonary bypass, the dose of unfractionated heparin for anticoagulation through a central venous catheter is 300-400 U/kg, with additional doses as necessary to achieve and maintain an activated coagulation time (ACT) between 480 and 600 seconds. After isolation from cardiopulmonary bypass, heparin-induced anticoagulation was reversed with protamine. Surgical procedures include coronary artery bypass grafting, heart valve replacement, aortic replacement, etc.
* Ulinastatin group: On the basis of conventional treatment, administered in accordance with the instructions or previous study doses (general anesthesia with endotracheal intubation, after cardiopulmonary bypass transfer started): 10,000 U/kg Ulinastatin (Guoyao Zhunzi H19990134 , Guangdong Tianpu Biochemical Pharmaceutical Co., Ltd., Guangzhou, China) was dissolved in 50 ml of normal saline for 1 hour through central venous infusion.
After cardiopulmonary bypass
* operation time
* Vital signs (temperature, pulse, respiration, blood pressure)
* Routine blood chemistry and arterial blood gas analysis
* Document vasoactive drug use
3. 24 hours, 72 hours, 7 days after surgery
* Vital signs (temperature, pulse, respiration, blood pressure)
* Bedside echocardiography
* Laboratory tests (blood routine, blood sugar, blood lipids, liver and kidney function, myocardial enzymes, coagulation function, etc.)
* After collecting the above blood samples for testing, the remaining blood is centrifuged, and the plasma is frozen at -80°C for later testing (levels of CRP, IL-6, IL-10, TNF-α, TK/B1R/MMP3, etc.)
* Capillary leak indicators
* Document treatment regimen (including vasoactive drug use, etc.)
4. Follow-up period
* CCU time and total hospital stay
* 28-day survival status The survival status of the patients was followed up, and the date of death and the cause of death should be recorded in the patients who died.
5. Research Evaluation 1) Main efficacy indicators: cardiac function (echocardiography EF, FS), inflammatory indicators (CRP, IL-6, IL-10, TNF-α), TK/B1R/MMP3 and other levels at 24h, 72h, and 7d after surgery 2) Secondary efficacy indicators: coagulation function, capillary leakage index, 28-day survival rate, CCU time, total hospital stay.
6. Patient Completion/Withdrawal from Study Finish All evaluation data of the patients 28 days after the operation were completely collected and considered as completed cases.
withdraw from the study
Patients will be withdrawn from the study if:
* Patient selection errors
* Intraoperative and postoperative cardiac arrest due to non-CPB causes
* The patient has a drug allergy
* Patient withdraws informed consent
* Any situation in which the investigator believes that the patient should discontinue the study for safety reasons or the patient's interest
* Patient lost to follow-up
* other The date and reason for termination of the study must be recorded on the data collection form. At the time of study termination, patients should be assessed for their final endpoints, in addition to loss to follow-up.
* Sign informed consent
* Check inclusion/exclusion criteria
* Demographic data (sex, age, occupation, etc.)
* Past medical history (stroke, hypertension, diabetes, dyslipidemia, coronary heart disease, diabetes, etc.) and medication history in the past 3 months
* Vital signs (temperature, pulse, respiration, blood pressure)
* Preoperative ECG
* Preoperative echocardiography
* Laboratory tests (blood routine, blood glucose, blood lipids, liver and kidney function, myocardial enzymes, blood electrolytes, coagulation function)
* Concomitant therapy
* Adverse events
2. Intraoperative cardiopulmonary bypass
* Record vital signs and various physiological indicators in the operating room.
* Routinely perform central venous puncture to establish venous access and monitor central venous pressure, and radial artery puncture to monitor invasive arterial pressure.
* After general anesthesia and endotracheal intubation, routine blood chemistry and arterial blood gas analysis were performed.
* After collecting the above blood samples for testing, the remaining blood was centrifuged, and the plasma was frozen at -80°C for subsequent testing (levels of CRP, IL-6, IL-10, TNF-α, TK/B1R/MMP3, etc.).
* Conventional treatment group: On the basis of general anesthesia, the extracorporeal circulation circuit was routinely prefilled. Management of CPB includes blood gas acid-base electrolyte management, anticoagulation management, invasive arterial blood pressure monitoring, MAP in the range of 50-80 mmHg, hematocrit maintained at 20-25%, and non-pulsatile flow rate of 2.0-2.4 L/min/ m2. During cardiopulmonary bypass, the dose of unfractionated heparin for anticoagulation through a central venous catheter is 300-400 U/kg, with additional doses as necessary to achieve and maintain an activated coagulation time (ACT) between 480 and 600 seconds. After isolation from cardiopulmonary bypass, heparin-induced anticoagulation was reversed with protamine. Surgical procedures include coronary artery bypass grafting, heart valve replacement, aortic replacement, etc.
* Ulinastatin group: On the basis of conventional treatment, administered in accordance with the instructions or previous study doses (general anesthesia with endotracheal intubation, after cardiopulmonary bypass transfer started): 10,000 U/kg Ulinastatin (Guoyao Zhunzi H19990134 , Guangdong Tianpu Biochemical Pharmaceutical Co., Ltd., Guangzhou, China) was dissolved in 50 ml of normal saline for 1 hour through central venous infusion.
After cardiopulmonary bypass
* operation time
* Vital signs (temperature, pulse, respiration, blood pressure)
* Routine blood chemistry and arterial blood gas analysis
* Document vasoactive drug use
3. 24 hours, 72 hours, 7 days after surgery
* Vital signs (temperature, pulse, respiration, blood pressure)
* Bedside echocardiography
* Laboratory tests (blood routine, blood sugar, blood lipids, liver and kidney function, myocardial enzymes, coagulation function, etc.)
* After collecting the above blood samples for testing, the remaining blood is centrifuged, and the plasma is frozen at -80°C for later testing (levels of CRP, IL-6, IL-10, TNF-α, TK/B1R/MMP3, etc.)
* Capillary leak indicators
* Document treatment regimen (including vasoactive drug use, etc.)
4. Follow-up period
* CCU time and total hospital stay
* 28-day survival status The survival status of the patients was followed up, and the date of death and the cause of death should be recorded in the patients who died.
5. Research Evaluation 1) Main efficacy indicators: cardiac function (echocardiography EF, FS), inflammatory indicators (CRP, IL-6, IL-10, TNF-α), TK/B1R/MMP3 and other levels at 24h, 72h, and 7d after surgery 2) Secondary efficacy indicators: coagulation function, capillary leakage index, 28-day survival rate, CCU time, total hospital stay.
6. Patient Completion/Withdrawal from Study Finish All evaluation data of the patients 28 days after the operation were completely collected and considered as completed cases.
withdraw from the study
Patients will be withdrawn from the study if:
* Patient selection errors
* Intraoperative and postoperative cardiac arrest due to non-CPB causes
* The patient has a drug allergy
* Patient withdraws informed consent
* Any situation in which the investigator believes that the patient should discontinue the study for safety reasons or the patient's interest
* Patient lost to follow-up
* other The date and reason for termination of the study must be recorded on the data collection form. At the time of study termination, patients should be assessed for their final endpoints, in addition to loss to follow-up.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: