Topical Effect of Tranexamic Acid in Postoperative Bleeding and Blood Products Transfusion After Cardiac Surgery

NCT ID: NCT05708690

Last Updated: 2023-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-01
• Study Completion Date: 2023-01-06

Brief Summary

This is a single-center, double-blind, randomized controlled trial (RCT) comparing two groups of application of topical dose of tranexamic acid (TxA) versus placebo in patients undergoing coronary artery bypass graft (CABG), off pump coronary bypass graft cardiac surgery (OPCAB), and adult heart valve surgery. The primary outcomes of this study comprised of two parameters; post operative bleeding and blood product transfusion. The primary outcomes were assessed during the operation, until 48-hour post operative.

Detailed Description

A single center randomized controlled trial (RCT) was conducted at Harapan Kita National Cardiovascular Center, Jakarta, Indonesia as the tertiary cardiovascular referral hospital. The RCT was conducted from October 1 th, 2022 until January 6 th, 2023 (current status: completed). This study aims to determine whether topical tranexamic acid is more effective on the amount of bleeding and the need for postoperative blood product transfusion compared with placebo in patients undergoing cardiac surgery and specifically measure the difference outcome between coronary artery bypass graft (CABG), off pump coronary bypass graft cardiac surgery (OPCAB), and adult heart valve surgery. The control group in this study is given 100 mL of normal saline. The subjects were adults undergoing elective cardiac surgery (CABG, OPCAB, and heart valve surgery). Both the patients and the principal investigators were blinded for the treatment-control allocation. The patients were purposively selected and were randomly assigned to one of the arms with block randomization. The primary outcomes of this study comprised of two parameters; post operative bleeding and blood product transfusion. The primary outcomes were assessed during the operation, until 48-hour post operative.

Conditions

Coronary Artery Disease; Valvular Heart Disease; Surgical Blood Loss

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Tranexamic Acid Topical

The treatment of interest was application of Topical Tranexamic Acid (5 gram in 50 mL warm normal saline). The topical will be poured into the pericardial and mediastinal cavities (after protamine administration), and sternum (before chest closure)

Group Type: EXPERIMENTAL

Tranexamic Acid 100 MG/ML

Intervention Type: DRUG

Tranexamic acid is a synthetic derivative of lysine used as an antifibrinolytic in the treatment and prevention of major bleeding. Tranexamic acid competitively and reversibly inhibits the activation of plasminogen via binding at several distinct sites, including four or five low-affinity sites and one high-affinity site, the latter of which is involved in its binding to fibrin. The binding of plasminogen to fibrin induces fibrinolysis - by occupying the necessary binding sites tranexamic acid prevents this dissolution of fibrin, thereby stabilizing the clot and preventing hemorrhage

Placebo

The control group is given 100 mL of warm normal saline. The topical will be poured into the pericardial and mediastinal cavities (after protamine administration), and sternum (before chest closure).

Group Type: PLACEBO_COMPARATOR

normal saline

Intervention Type: DRUG

Normal saline is a cornerstone of intravenous solutions commonly used in the clinical setting. It is a crystalloid fluid administered via an intravenous solution. Its indications include both adult and pediatric populations as sources of hydration and electrolyte disturbances

Interventions

Tranexamic Acid 100 MG/ML

Tranexamic acid is a synthetic derivative of lysine used as an antifibrinolytic in the treatment and prevention of major bleeding. Tranexamic acid competitively and reversibly inhibits the activation of plasminogen via binding at several distinct sites, including four or five low-affinity sites and one high-affinity site, the latter of which is involved in its binding to fibrin. The binding of plasminogen to fibrin induces fibrinolysis - by occupying the necessary binding sites tranexamic acid prevents this dissolution of fibrin, thereby stabilizing the clot and preventing hemorrhage

Intervention Type: DRUG

normal saline

Normal saline is a cornerstone of intravenous solutions commonly used in the clinical setting. It is a crystalloid fluid administered via an intravenous solution. Its indications include both adult and pediatric populations as sources of hydration and electrolyte disturbances

Intervention Type: DRUG

Other Intervention Names

Tranexamic Acid

Eligibility Criteria

Inclusion Criteria

• Patients ages > 18 years old
• Patients who are scheduled electively for cardiac surgery in National Heart Center Harapan Kita, Jakarta, Indonesia
• Patients with heart valve disease indicated for aortic or mitral repair/replace
• Patients with coronary artery disease indicated for CABG or OPCAB surgery
• Aortic and/ mitral valve surgery concomitant with tricuspid repair
• Patients who are agreed to participate in this study

Exclusion Criteria

• Not willing to become research subjects
• Allergy to tranexamic acid
• Undergoing minimally invasive surgery
• Undergoing double valve (aorta & mitral) procedure and double procedure (CABG+valve, valve+maze)
• Emergency surgery
• History of bleeding disorder or coagulopathy
• History of thromboembolic or hemorrhagic disease
• Active Infective endocarditis
• History of previous cardiac surgery
• Estimated glomerular filtration rate <30 mL/min or on dialysis
• Receiving oral therapy with clopidogrel, aspirin, dabigatran, or rivaroxaban in the last five days
• Receiving chronic warfarin therapy who have not stopped their medication and have an international normalized ratio (INR) >1.5 before surgery
• Pre-operative thrombocytopenia (<50,000 platelets per µL)
• Pregnancy or breast feeding
• Refusal of blood products
• Pericarditis

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Indonesia University

OTHER

Sponsor Role: lead

Responsible Party

Dudy Arman Hanafy, Sp. BTKV (K), MARS

Dr.dr.Dudy Arman Hanafy, Sp.BTKV(K)-D, MARS

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Komite Etik Pusat Jantung Nasional Harapan Kita

Role: STUDY_CHAIR

Ethical Committee of National Cardiovascular Center Harapan Kita

Locations

National Cardiovascular Center Harapan Kita

Jakarta, DKI Jakarta, Indonesia

Countries

Indonesia

References

Ausen K, Pleym H, Liu J, Hegstad S, Nordgard HB, Pavlovic I, Spigset O. Serum Concentrations and Pharmacokinetics of Tranexamic Acid after Two Means of Topical Administration in Massive Weight Loss Skin-Reducing Surgery. Plast Reconstr Surg. 2019 Jun;143(6):1169e-1178e. doi: 10.1097/PRS.0000000000005620.

Reference Type: BACKGROUND

PMID: 31136475 (View on PubMed)

Ker K, Beecher D, Roberts I. Topical application of tranexamic acid for the reduction of bleeding. Cochrane Database Syst Rev. 2013 Jul 23;2013(7):CD010562. doi: 10.1002/14651858.CD010562.pub2.

Reference Type: BACKGROUND

PMID: 23881695 (View on PubMed)

Habbab LM, Hussain S, Power P, Bashir S, Gao P, Semelhago L, VanHelder T, Parry D, Chu V, Lamy A. Decreasing Postoperative Blood Loss by Topical vs. Intravenous Tranexamic Acid in Open Cardiac Surgery (DEPOSITION) study: Results of a pilot study. J Card Surg. 2019 May;34(5):305-311. doi: 10.1111/jocs.14027. Epub 2019 Mar 25.

Reference Type: RESULT

PMID: 30908754 (View on PubMed)

Abul-Azm A, Abdullah KM. Effect of topical tranexamic acid in open heart surgery. Eur J Anaesthesiol. 2006 May;23(5):380-4. doi: 10.1017/S0265021505001894. Epub 2006 Jan 27.

Reference Type: RESULT

PMID: 16438759 (View on PubMed)

Baric D, Biocina B, Unic D, Sutlic Z, Rudez I, Vrca VB, Brkic K, Ivkovic M. Topical use of antifibrinolytic agents reduces postoperative bleeding: a double-blind, prospective, randomized study. Eur J Cardiothorac Surg. 2007 Mar;31(3):366-71; discussion 371. doi: 10.1016/j.ejcts.2006.12.003. Epub 2007 Jan 10.

Reference Type: RESULT

PMID: 17218108 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1706120543

Identifier Type: OTHER

Identifier Source: secondary_id

1706120530

Identifier Type: OTHER

Identifier Source: secondary_id

TRACS

Identifier Type: -

Identifier Source: org_study_id