Strategies for Protamine Dosing After Anticoagulation in Cardiovascular Surgery

Anticoagulant Antagonist Toxicity Clinical Trial

— SEPARATION  

Official title:

Comparison of Two Strategies for Protamine Dosing After Anticoagulation in Cardiovascular Surgery Regarding Postoperative Bleeding: Total Heparin Administered Versus Residual Heparin Determined by a Pharmacokinetic Model

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04628884
• Other study ID #: DIB-20-34
• Status: Recruiting
• Phase: Phase 4
• Start date: November 15, 2020
• Est. completion date: November 22, 2021

Study information

• Verified date: November 2020
• Source: Fundación Clínica Shaio
• Contact: Fabian Cortez, MSc
• Phone: +57 (1) 593 8210
• Email: fabian.cortes[@]shaio.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In cardiovascular surgery, patients are anticoagulated with heparin during cardiopulmonary bypass, subsequently, anticoagulation is reversed with protamine to reduce bleeding due to residual heparin-induced coagulopathy, which can last more than four hours. Protamine reverses the effect of heparin by binding to each heparin molecule, therefore an amount of protamine equivalent to residual heparin is required at the time that anticoagulation is desired to be reversed, but generally, the dose of protamine is calculated from the total dose of heparin, ignoring that heparin is metabolized and cleared during of the extracorporeal circulation, this excess of protamine produces anticoagulant effects that increase postoperative bleeding. Residual heparin can be estimated from heparin pharmacokinetic models and therefore, from these models, a dose closer to the amount necessary to reverse the effect of heparin can be estimated, avoiding protamine excess. In this study, a protamine dosage strategy based on residual heparin determined by a pharmacokinetic model of heparin versus total administered heparin will be compared regarding bleeding and use of blood components in the postoperative period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 136
• Est. completion date: November 22, 2021
• Est. primary completion date: November 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients over 18 years of age who undergo scheduled cardiovascular surgery or scheduled urgency at the Shaio clinical foundation in the city of Bogotá, who require extracorporeal circulation.

• ASA classification, between 1 - 4

• Informed consent read and signed by the patient

• No history of known blood dyscrasia, with INR values <1.5

• Platelet count greater than 100,000

• No history of heparin-induced thrombocytopenia

• No history of adverse reaction to protamine

• No use of dual anti-aggregation therapy acetylsalicylic acid (ASA) + ADP receptor inhibitors (Clopidogrel) at the time of surgery

• Suspension of ADP receptor inhibitor drugs (Clopidogrel) according to institutional protocol.

• No use of bridging therapy with tirofiban

• Patient with chronic use of oral anticoagulants (warfarin, dabigatran), complete the suspension time according to the institutional protocol,

• No requirement for renal replacement therapy in the last month

• Patient with BMI between 18 - 41 kg / cm2

• Not pregnant

Exclusion Criteria:

• Emergency surgery

• Anticoagulated patient at the time of the intervention

• Procedure not performed under extracorporeal circulation.

• Procedure requiring circulatory arrest and / or profound hypothermia

• Intraoperative death before protamine administration

• Inability to complete data collection.

Related Conditions & MeSH terms

• Anticoagulant Antagonist Toxicity

Intervention

Drug:
• Conventional dose
Conventional dose used to calculated the protamine dose
• Dosing according residual heparin
In this group the heparin doses will be simulated using a pharmacokinetic model to estimated the residual heparin amount at the end of the surgery, the protamine dose will be calculated using the residual heparin

Locations

Country	Name	City	State
Colombia	Fundacion Abood Shaio	Bogotá

Sponsors (2)

Lead Sponsor	Collaborator
Fundación Clínica Shaio	Universidad El Bosque, Bogotá

Country where clinical trial is conducted

Colombia, 

References & Publications (3)

Delavenne X, Ollier E, Chollet S, Sandri F, Lanoiselée J, Hodin S, Montmartin A, Fuzellier JF, Mismetti P, Gergelé L. Pharmacokinetic/pharmacodynamic model for unfractionated heparin dosing during cardiopulmonary bypass. Br J Anaesth. 2017 May 1;118(5):705-712. doi: 10.1093/bja/aex044. — View Citation

Meesters MI, Veerhoek D, de Jong JR, Boer C. A Pharmacokinetic Model for Protamine Dosing After Cardiopulmonary Bypass. J Cardiothorac Vasc Anesth. 2016 Oct;30(5):1190-5. doi: 10.1053/j.jvca.2016.04.021. Epub 2016 Apr 28. — View Citation

Puis L, Milojevic M, Boer C, De Somer FMJJ, Gudbjartsson T, van den Goor J, Jones TJ, Lomivorotov V, Merkle F, Ranucci M, Kunst G, Wahba A; EACTS/EACTA/EBCP Committee Reviewers. 2019 EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass in adult cardiac surgery. Interact Cardiovasc Thorac Surg. 2020 Feb 1;30(2):161-202. doi: 10.1093/icvts/ivz251. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	postoperative mediastinal bleeding	total blood collected from the mediastinal chest tubes during the first 24 hours	first 24 hours after surgery
Secondary	total blood products transfused	red blood cells, plasma, cryoprecipitate, platelets, fibrinogen, and prothrombin complexes	first 24 hours after surgery