Heparin Antagonization by Protamine in Cardiac Surgery: Pharmacokinetic/Pharmacodynamic Study

Completed

• Conditions: Cardiac Surgery Requiring Extracorporeal Circulation
• Interventions: Other: Blood samples PK/ PD protamine

• Registration Number: NCT04092868
• Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne

Brief Summary

Protamine is currently used during cardiac surgery to neutralize unfractionated heparin (UFH) at the end of extra-corporeal circulation (ECC). The optimal dose of protamine is currently unknown, and the administration of protamine is done empirically.

Protamine and UFH pharmacokinetics are characterized by a large inter-individual variability. A dose of protamine proportional to the amount of UFH administrated during the surgery may be therefore not adapted to most of the patients and exposed them to a risk of under or over dosage.

In this study, research investigators hypothesize that an accurate characterization of the pharmacokinetic/pharmacodynamic (PK/PD) relationship of protamine may help to optimize propose an optimal dosing regimen.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-09
• Study First Submitted QC: 2019-09-16
• Study First Posted: 2019-09-17
• Study Start: 2019-11-13
• Status Verified: 2021-03
• Primary Completion: 2021-03-12
• Study Completion: 2021-03-12
• Last Update Submitted: 2021-03-25
• Last Update Posted: 2021-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• Patients benefiting from scheduled or emergency at the Saint-Etienne University Hospital (coronary artery bypass grafting, valve replacements, aortic dissections).

Exclusion Criteria

• Patients with a contraindication to UFH
• Patients with a contraindication to protamine
• Patients requiring early resurgery.
• Patients receiving an injection of antithrombin III.
• Pregnant women.
• Patient for whom aprotinin use is planned during surgery.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
cardiac surgery with extracorporeal circulation	Blood samples PK/ PD protamine	during the operation Intervention Blood sample : - Choay Heparin (pharmacokinetic) concentration: t = 5, 15, 30 minutes after the start of the heparin injection + t = 5, 30, 60 minutes after the start of extracorporeal circulation * protamine dosage: t = 2, 5, 8, 10 and 15 min after protamine injection * anti-X activity t = 0 before administration and at time 2, 5, 8, 10 and 15 min then at time 1, 3, 5, 6 and 7 hours after protamine injection * thrombin generation test (TGT) activity (thrombinography) : t = 2, 5, 8, 10 and 15 min after protamine injection

Primary Outcome Measures

Name	Time	Method
PK/PD Protamine	1 day	Pharmacokinetics (PK) : plasma concentration of protamine measured by liquid chromatography coupled with mass spectrometry.; Pharmacodynamics (PD) :The effect of protamine corresponds to the kinetics of the disappearance of UFH in the blood. To do this, the investigators measure its concentration using an anti-Xa activity measurement technique.

Secondary Outcome Measures

Name	Time	Method
PK/PD Protamine	1 day	PK: evolution of protamine concentrations over time (plasma concentration of protamine measured by liquid chromatography coupled with mass spectrometry).; PD: ts neutralizing effect evaluated by thrombinography .
postoperative blood loss:	1 day	quantities of blood loss in pleural and mediastinal drains during the first 24 hours postoperatively.
ratios between the amount of UFH present at the protamine injection and the dose of protamine administered.	1 day

Trial Locations

Locations (1)

CHU Saint-Etienne; 🇫🇷 Saint-Étienne, France