Anticoagulation Management in Complex Cardiac Surgery

Impact on Anticoagulation Management When Activated Clotting Time is Combined With Heparin Concentration Monitoring in Cardiac Surgery: a Randomised Clinical Trial

The goal of this clinical trial is to compare the anticoagulation management with or without heparin concentration level guidance, in patients undergoing valve or complex cardiac surgery during cardiopulmonary bypass using closed, coated circuits. The main questions it aims to answer are:

• initial heparin bolus, subsequent supplementary doses and total heparin variance among groups.
• protamine dose among groups.

Participants are adult patients scheduled for valve or complex cardiac surgery. They are randomised to either Activated Clotting Time guided management alone or combined with heparin level concentration monitoring.

Study Overview

• Status: Completed
• Conditions: Extracorporeal Circulation
• Intervention / Treatment: Other: Activated Clotting Time; Other: Activated Clotting Time measurements combined with heparin concentration monitoring

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki, Greece, 54124
    • AHEPA University Hospital, Aristotle University of Thessaloniki

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• elective procedures
• cardiac surgery, except for Coronary Artery Bypass Grafting
• Cardiopulmonary bypass under Minimally Invasive Extracorporeal Circulation

Exclusion Criteria:

• known allergy to heparin or protamine
• hematological disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Activated Clotting Time (ACT); In this group, only ACT measurements and fixed doses of heparin and protamine are administered. ACT is measured using the ACT Plus device (Medtronic, MN, USA). Heparin formulation administered is HEPARIN/LEO INJ.SOL 25000IU/5ML. Protamine formulation administered is PROTAMINE SULPHATE/LEO PHARMA 10mg/ml	Other: Activated Clotting Time; The target ACT for procedures other than Coronary Artery Bypass Grafting (CABG) is 400s when Minimally Invasive Extracorporeal Circulation is used. A bolus of 300 International Units(IU)/kg heparin are administered to reach this target and initiate cardiopulmonary bypass (CPB). Repeated ACT measurements guide further heparin dose to maintain adequate anticoagulation. Then, at the end of the CPB, 0.75 mg of protamine are administered for every 100IU of the initial heparin bolus.
Active Comparator: Heparin Concentration (HC); In this group, the Hepcon HMS Plus (Medtronic, MN, USA) is used to perform heparin concentration calculations and test each patient's individual response to heparin. Specifically tests performed were: Heparin Dose Response test; Heparin Assay test	Other: Activated Clotting Time measurements combined with heparin concentration monitoring; In the HC group, the initial heparin dose is calculated using the HepCon HMS Plus . Except for ACT, heparin concentration is measured to maintain target heparin levels during CPB. The protamine dose for reversal is computed based on actual measured heparin levels using the device. ACT is also performed in all instances.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heparin dose	Heparin dose, IU	Bolus dose before cardiopulmonary bypass
Heparin dose	Heparin dose, IU	Total dose after cardiopulmonary bypass
Protamine dose	Protamine dose, mg	Total dose after cardiopulmonary bypass

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet count	Platelet count per mm^3	Immediately after surgery
Platelet count	Platelet count per mm^3	24 hours after surgery
Platelet count	Platelet count per mm^3	48 hours after surgery

Collaborators and Investigators

• Sponsor: Aristotle University Of Thessaloniki
• Investigators: Study Director: Helena Argiriadou, Dr, AHEPA University Hospital, Aristotole University of Thessaloniki

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): February 20, 2023

Study Registration Dates

• First Submitted: June 24, 2023
• First Submitted That Met QC Criteria: July 11, 2023
• First Posted (Actual): July 13, 2023

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: cardiopulmonary bypass; anticoagulation; heparin; titration
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin
• Other Study ID Numbers: 3432

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No