Hemostatic Effects of Ulinastatin and Tranexamic Acid in Cardiac Surgery

Hemostatic Effects of Ulinastatin and Tranexamic Acid in Cardiac Surgery With Cardiopulmonary Bypass: A Pilot Study

Antifibrinolytic drugs are used to decrease perioperative bleeding and allogeneic transfusions. The extensively studied antifibrinolytic drug aprotinin is efficacious but expensive, and has been proved to link to higher risks of serious side effects including renal problems, myocardial events, and strokes in patients undergoing CABG. After the secession of aprotinin in 2007, a marked increase of blood loss and transfusions in cardiac surgery took place. An effective and secure hemostatic agent is badly needed. Ulinastatin, urinary trypsin inhibitor(UTI), is a secreted Kunitz-type protease inhibitor with a wide inhibition spectrum, including plasmin. Limited studies offered clues to its antifibrinolytic effect. Tranexamic acid has been applied for years with convinced efficacy and safety. The objective of the study is to evaluate the hemostatic effect of ulinastatin and tranexamic acid in cardiac surgery.

Study Overview

• Status: Completed
• Conditions: Hemostasis
• Intervention / Treatment: Drug: Tranexamic Acid; Drug: Ulinastatin; Drug: Saline Solution

• Study Type: Interventional
• Enrollment (Actual): 426
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100037
      • Cardiovascular Institute and Fuwai Hospital, CAMS&PUMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Atrial or ventricular septum defect patients requiring cardiac surgery with CPB
• Rheumatic or recessive valvular patients requiring valvular repair or replacement with CPB
• Coronary artery disease patients requiring coronary revascularization surgery with CPB

Exclusion Criteria:

• Non-primary cardiac surgery
• Definite liver or renal dysfunction
• Disorder in coagulation function
• Allergy
• Pregnancy or lactation
• Disabled in spirit or law
• Fatal conditions such as tumour

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ulinastatin; 1,000,000 units of ulinastatin in 50ml solution before skin incision; 50ml saline solution after neutralization	Drug: Ulinastatin
Experimental: Tranexamic Acid; 15mg/kg tranexamic acid in 50ml solution before skin incision; 15mg/kg tranexamic acid in 50ml solution after neutralization	Drug: Tranexamic Acid
Placebo Comparator: Placebo; 50ml saline solution before skin incision; 50ml saline solution after neutralization	Drug: Saline Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative blood loss	Defined as the total volume of chest drainage postoperatively	Postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of reexploration for bleeding		Postoperatively
Rate of major bleeding	Major bleeding is defined according to the CURE study	Perioperatively
Transfusion of allogeneic erythrocytes	Rate of exposure and volume of allogeneic erythrocytes transfused	Perioperatively
Transfusion of fresh frozen plasma (FFP)	Rate of exposure and volume of FFP transfused	Perioperatively
Transfusion of allogeneic platelets	Rate of exposure and volume of allogeneic platelets transfused	Perioperatively
Length of stay in ICU and hospital postoperatively		Postoperatively

Collaborators and Investigators

• Sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
• Investigators: Principal Investigator: Jia Shi, MD, Cardiovascular Institute and Fuwai Hospital, CAMS&PUMC; Study Chair: Lihuan Li, MD, Cardiovascular Institute and Fuwai Hospital, CAMS&PUMC

Publications and helpful links

General Publications

• Zhang P, Lv H, Qi X, Xiao W, Xue Q, Zhang L, Li L, Shi J. Effect of ulinastatin on post-operative blood loss and allogeneic transfusion in patients receiving cardiac surgery with cardiopulmonary bypass: a prospective randomized controlled study with 10-year follow-up. J Cardiothorac Surg. 2020 May 14;15(1):98. doi: 10.1186/s13019-020-01144-9.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2008
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: January 28, 2010
• First Submitted That Met QC Criteria: February 1, 2010
• First Posted (Estimate): February 2, 2010

Study Record Updates

• Last Update Posted (Actual): February 5, 2019
• Last Update Submitted That Met QC Criteria: February 2, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: tranexamic acid; hemostasis; ulinastatin; cardiac surgery procedures
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrin Modulating Agents; Protease Inhibitors; Serine Proteinase Inhibitors; Antifibrinolytic Agents; Hemostatics; Coagulants; Trypsin Inhibitors; Tranexamic Acid; Urinastatin
• Other Study ID Numbers: UTI Pilot Study