Clinical trial NCT04628884: Strategies for Protamine Dosing After Anticoagulation in Cardiovascular Surgery
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Anticoagulant Antagonist Toxicity
Keywords: heparin
protamine
dose
extracorporeal circulation
cardiopulmonary bypass
Lead sponsor: Fundación Clínica Shaio
Sponsor class: OTHER
Collaborators: name: Universidad El Bosque, Bogotá
First posted: 2020-11-16
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: postoperative mediastinal bleeding
timeFrame: first 24 hours after surgery
Secondary outcomes:
measure: total blood products transfused
timeFrame: first 24 hours after surgery
Other outcomes:
Locations:
city: Bogotá
country: Colombia
facility: Fundacion Abood Shaio
Study officials:
affiliation: Fundacion Abood Shaio
name: Mauricio Abello
role: STUDY_CHAIR
affiliation: Universidad del bosque
name: David Ramez
role: PRINCIPAL_INVESTIGATOR
References:
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. No abstract available.
citation: Delavenne X, Ollier E, Chollet S, Sandri F, Lanoiselee J, Hodin S, Montmartin A, Fuzellier JF, Mismetti P, Gergele 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.
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.