Outcome Impact of Different Tranexamic Acid Regimen in Cardiac Surgery With Cardiopulmonary Bypass (OPTIMAL)

November 27, 2021 updated by: SHI Jia, Chinese Academy of Medical Sciences, Fuwai Hospital

Outcome Impact of Different Tranexamic Acid Regimen in Cardiac Surgery With Cardiopulmonary Bypass (the OPTIMAL Study)

Background and Significance A growing amount of evidence linking transfusion of allogeneic blood products with negative patient outcomes and increased cost continues to drive interest into strategies and technologies that limit patient exposure to this risk. The single largest consumer of this resource continues to be cardiac surgery, with 20% of the world wide use of allogeneic blood products accounted for by this cohort. The lysine analogs tranexamic acid (TXA) has gained wide spread use in cardiac surgery as a blood-sparing agent. Mounted evidence has proved its efficacy and safety in cardiac surgery. However, the optimal dose regimen of TXA and the impact on patients' outcomes remains debated.

Study Objectives The primary objective of the study is to analyze the primary efficacy (superiority) and primary safety (non-inferiority) of the two dose regimen of tranexamic acid.. The primary efficacy endpoint includes perioperative allogeneic transfusion rate, and the primary safety endpoint includes the 30-day rate of the composite of perioperative renal dysfunction, myocardial infarction, ischaemic stroke, seizure, deep venous thrombosis, pulmonary embolism and all-cause mortality. The secondary objectives are to demonstrate the efficacy of the two dose regimens in reducing perioperative allogeneic transfusion volume, postoperative bleeding (chest tube drainage), reoperation rate, mechanic ventilation duration, ICU stay, hospital length of stay (LOS), and total hospitalization cost.

Study Endpoints The primary endpoints include efficacy and safety. The primary efficacy endpoint includes perioperative allogeneic transfusion rate, and the primary safety endpoint includes the 30-day rate of the composite of perioperative renal dysfunction, myocardial infarction, ischaemic stroke, seizure, deep venous thrombosis, pulmonary embolism, and all-cause mortality. The key secondary endpoints of the study are defined as perioperative allogeneic transfusion volume, postoperative bleeding (chest tube drainage), reoperation rate, mechanic ventilation duration, ICU stay, hospital length of stay (LOS), and total hospitalization cost.

Study Population Adult patients aged 18-70 years undergoing elective cardiac surgery with cardiopulmonary bypass are included. Totally 3008 patients will be required for this study (1504 in each of the 2 groups).

Study Design The study is a multicenter, randomised, double-blind trial. Cardiac surgery patients with cardiopulmonary bypass will be randomised to Dosage 1 regimen group or Dosage 2 regimen group of tranexamic acid.

Study Treatment The dosage regimen is implemented with dose of loading (intravenous infusion in 20 mins), maintenance (throughout the surgery), and pump prime (added into the bypass machine). The Dosage 2 regimen contains an intravenous bolus of 10 mg/kg after anesthetic induction followed by an intravenous maintenance of 2 mg/kg/h throughout the surgery, and a pump prime dose 1 mg/kg. As for the Dosage 1 regimen, the intravenous bolus and the maintenance are 30 mg/kg and 16 mg/kg/h respectively, and a pump prime dose 2 mg/kg. Patients, surgeons and research staff interviewing patients postoperatively will be blind to treatment allocation.

Statistical Considerations The study hypothesis is that the Dosage 1 regimen of tranexamic acid is superiority to the Dosage 2 regimen in the primary efficacy endpoint, while at the same time, the Dosage 1 regimen is non-inferiority to the Dosage 2 regimen in the primary safety endpoint in cardiac surgery with cardiopulmonary bypass. The sample size calculation is mainly based on the blood transfusion rate, and 30-day rate of the composite of perioperative renal dysfunction, myocardial infarction, ischaemic stroke, seizure, deep venous thrombosis, pulmonary embolism and all-cause mortality. For the primary efficacy endpoint, a sample size estimate of 1,214 randomized subjects (607 for each group) has 90% power to detect a 12.5% reduction (61.7% vs 70.5% between Dosage 1 regimen and Dosage 2 regimen ), by means of a single-sided α = 0.025 Chi-square test. For the primary safety endpoint, a sample size estimate of 2,698 randomized subjects (1349 for each group) has 90% power to detect a noninferiority margin for the difference of 5%, by means of a single-sided α = 0.025 log rank test. In order to conduct an interim analysis, the sample size in each group is 1504(10% drop-out rate) for the adjusted significance level (from 0.025 to 0.0245 in accordance with α spending function by Lan-DeMets Method). Finally, the investigators decided to enroll 3008 study patients (1:1 ratio) for the OPTIMAL trial.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A face to face visit (review in hospital, or remote video interview via smart phone and social media) is required to screen the occurrence of 30-day rate of the composite endpoints of renal dysfunction, myocardial infarction,stroke, seizure, deep venous thrombosis, pulmonary embolism and all-cause mortality, specific examinations are needed to confirm the diagnosis.

Study Type

Interventional

Enrollment (Actual)

3079

Phase

  • Phase 4

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
      • Beijing, China, 100037
        • Chinese Academy of Medical Sciences, Fuwai Hospital

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

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female adult patients aged 18~70 years.
  2. Patients receiving cardiac surgery with cardiopulmonary bypass
  3. Written Informed consent obtained

Exclusion Criteria:

  1. Acquired chromatic disorder
  2. Active intravascular coagulation
  3. Previous convulsion or seizure
  4. Allergy or contraindication to tranexamic acid injection or its components
  5. Feeding or pregnancy women
  6. Terminal illness with a life expectancy of less than 3 months
  7. Patients with mental or legal disability
  8. Currently enrolled in another perioperative interventional study

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
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Tranexamic Acid Dosage 1
A bolus of 30 mg/kg Tranexamic Acid for 20 min followed by a maintenance dose of 16 mg/kg/h Tranexamic Acid until the end of surgery, and a pump prime dose 2 mg/kg.
Drug: Tranexamic Acid Dosage 1
Tranexamic Acid Dosage 1
Other Names:
  • Transamin
  • Cyklokapron
ACTIVE_COMPARATOR: Tranexamic Acid Dosage 2
A bolus of 10 mg/kg Tranexamic Acid for 20 min followed by a maintenance dose of 2 mg/kg/h Tranexamic Acid until the end of surgery, and a pump prime dose 1 mg/kg.
Drug: Tranexamic Acid Dosage 2
Tranexamic Acid Dosage 2
Other Names:
  • Transamin
  • Cyklokapron

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Perioperative allogeneic RBC transfusion rate
Time Frame: From the operation day to the discharge, an average of 7 days
The overall transfusion rate of allogeneic package RBC.
From the operation day to the discharge, an average of 7 days
Composite rate of renal dysfunction, myocardial infarction,stroke, seizure, deep venous thrombosis, pulmonary embolism and all-cause mortality
Time Frame: 30-day postoperatively
A face to face visit (review in hospital, or remote video interview via smart phone and social media) is required to screen the occurrence of 30-day rate of the composite endpoints of renal dysfunction, myocardial infarction,stroke, seizure, deep venous thrombosis, pulmonary embolism and all-cause mortality, specific examinations are needed to confirm the diagnosis.
30-day postoperatively

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Perioperative allogeneic RBC transfusion volume
Time Frame: From the operation day to the discharge, an average of 7 days
The overall volume of allogeneic transfused RBC
From the operation day to the discharge, an average of 7 days
Perioperative allogeneic non-RBC transfusion volume
Time Frame: From the operation day to the discharge, an average of 7 days
The overall volume of allogeneic transfused FFP，platelet，and cryoprecipitate
From the operation day to the discharge, an average of 7 days
Perioperative allogeneic non-RBC transfusion rate
Time Frame: From the operation day to the discharge, an average of 7 days
The rate of allogeneic transfused FFP，platelet，and cryoprecipitate
From the operation day to the discharge, an average of 7 days
Postoperative bleeding volume
Time Frame: From the operation day to the discharge, an average of 7 days
The total chest tube drainage postoperatively
From the operation day to the discharge, an average of 7 days
Reoperation rate for bleeding
Time Frame: From the operation day to the discharge, an average of 7 days
Reoperation due to excessive chest tube drainage or pericardial tamponade.
From the operation day to the discharge, an average of 7 days
The duration of mechanical ventilation
Time Frame: from the end of the operation and the extubation, an average of 24 hours
The time interval between the end of the operation and the extubation
from the end of the operation and the extubation, an average of 24 hours
Length of stay in the intensive care unit
Time Frame: From the end of the operation and the discharge from the intensive care unit, an average of 48 hours
The time interval between the end of the operation and the discharge from the intensive care unit
From the end of the operation and the discharge from the intensive care unit, an average of 48 hours
Length of stay in hospital
Time Frame: From the operation day to the discharge, an average of 7 days
The days between the operation and the discharge from the hospital
From the operation day to the discharge, an average of 7 days
Total hospitalization cost
Time Frame: In hospital, an average of 7 days
The total cost during hospitalization
In hospital, an average of 7 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Thrombotic test
Time Frame: preoperative、4~8 hours postoperative、1st postoperative day、2nd postoperative day、3rd postoperative day
D-dimer level
preoperative、4~8 hours postoperative、1st postoperative day、2nd postoperative day、3rd postoperative day
Correction Dimension of Electroencephalogram
Time Frame: 12 hours postoperatively
A reduced correction dimension of EEG indicates seizure
12 hours postoperatively
Bispectral Index
Time Frame: From anesthetic induction until 12 hours postoperatively, an average of 18 hours
A range of 0~100 (85~100 awake, 65~85 sedation, 40~65 anesthesia, <40 burst suppression)
From anesthetic induction until 12 hours postoperatively, an average of 18 hours
Drug concentration in plasma and cerebrospinal fluid
Time Frame: Fourteen timepoints from anesthetic induction until 6 hours postoperatively
Two mililiter of blood sample will be obtained from the radial artery in 8 participants in the two groups respectively. Two mililiter of cerebrospinal fluid will be obtained in 8 participants receiving aortic surgery with subarachnoid drainage in the two groups respectively.
Fourteen timepoints from anesthetic induction until 6 hours postoperatively

Collaborators and Investigators

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

Sponsor

Chinese Academy of Medical Sciences, Fuwai Hospital

Investigators

  • Principal Investigator: Zhe Zheng, MD, Chinese Academy of Medical Sciences, Fuwai Hospital

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)

December 26, 2018

Primary Completion (ACTUAL)

September 30, 2021

Study Completion (ACTUAL)

November 27, 2021

Study Registration Dates

First Submitted

December 17, 2018

First Submitted That Met QC Criteria

December 18, 2018

First Posted (ACTUAL)

December 20, 2018

Study Record Updates

Last Update Posted (ACTUAL)

November 30, 2021

Last Update Submitted That Met QC Criteria

November 27, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • the OPTIMAL study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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