Ulinastatin Improves and Prevents Cardiac Dysfunction Induced by Cardiopulmonary Bypass

January 17, 2025 updated by: Qin Zhang

Ulinastatin Improves and Prevents Cardiac Dysfunction Induced by Cardiopulmonary Bypass by Reducing Cardiac Endothelial Permeability

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
236

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Hubei
      • Wuhan, Hubei, China, 430030
        • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Voluntarily sign the informed consent;
  2. Age ≥18 years old and ≤70 years old;
  3. Patients receiving cardiopulmonary bypass
  4. Patients undergoing heart valve replacement surgery, major vascular surgery, and other cardiac surgery

Exclusion Criteria:

  1. Severe cardiac insufficiency before surgery (EF<50%, cardiogenic shock);
  2. Patients with adverse events during surgery (such as cardiac arrest, etc.);
  3. Solid organ or bone marrow transplant recipients;
  4. pregnant women;
  5. Have a history of allergy to ulinastatin or any of its ingredients;
  6. Suffering from autoimmune diseases, tumors, or received high-dose hormones, immunosuppressive drugs, etc. within 2 months;
  7. The researcher judges that it is not suitable to participate in this research.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Sham Comparator: Conventional treatment group
Cardiac surgery patients undergoing cardiopulmonary bypass are not treated with ulinastatin
Other: saline
On the basis of conventional treatment, 50 ml of normal saline for 1 hour and pumped through the central vein.
Experimental: Ulinastatin
Cardiac surgery patients undergoing cardiopulmonary bypass are treated with ulinastatin
Drug: Ulinastatin
On the basis of conventional treatment, according to the instructions or previous research doses (general anesthesia and tracheal intubation, after cardiopulmonary bypass transfer starts): 10,000 U/kg Ulinastatin (National Medicine Approval No. H19990134, Guangdong Tianpu Biochemical Pharmaceutical Co., Ltd. Co., Ltd., Guangzhou, China) was dissolved in 50 ml of normal saline for 1 hour and pumped through the central vein.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cardiac function
Time Frame: 24 hours
Echocardiographic detection
24 hours
Inflammatory markers
Time Frame: 24 hours
Detection of IL6
24 hours
TK/B1R/MMP3 signaling
Time Frame: 24 hours
Detection levels of tissue kallikrein, B1R and MMP3
24 hours
Inflammatory marker
Time Frame: 24 hours
Detection of CRP
24 hours
POD-postoperative delirium
Time Frame: 7 days
Assessment Method for the ICU (CAM-ICU
7 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Survival time
Time Frame: 28 days
Questionnaire
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Qin Zhang

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 16, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 31, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 6, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 10, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 17, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TJ-IRB20220831

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Study Data/Documents

  1. Clinical Study Report
    Information identifier: 28537661
    Information comments: Ulinastatin can effectively regulate the inflammatory cytokines and provide protection for organ function during cardiopulmonary bypass surgery, which is conducive to promote the recovery of patients.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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