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

Centre Hospitalier Universitaire de Saint Etienne

Status: Completed

Conditions: Cardiac Surgery Requiring Extracorporeal Circulation

Treatments: Other: Blood samples PK/ PD protamine

Study type: Observational

Funder types: Other

Identifiers

NCT04092868

19CH046

2019-000859-14 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 70 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

70 participants in 1 patient group

cardiac surgery with extracorporeal circulation

Description:

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

Treatment:

Other: Blood samples PK/ PD protamine