Strategies for Protamine Dosing After Anticoagulation in Cardiovascular Surgery

NCT ID: NCT04628884

Last Updated: 2020-12-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-15
• Study Completion Date: 2021-11-22

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.

Conditions

Anticoagulant Antagonist Toxicity

Keywords

heparin; protamine; dose; extracorporeal circulation; cardiopulmonary bypass

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Protamine dosing according the total heparin administrated

The protamine dose will be calculated according to the total heparin administered including the heparin dose add during the pump purge, 1 mg of protamine for each 100 IU of heparin

Group Type: ACTIVE_COMPARATOR

Conventional dose

Intervention Type: DRUG

Conventional dose used to calculated the protamine dose

Protamine dosing according the residual heparin determined by a pharmacokinetic model

The protamine dose will be calculated according to the residual heparin estimated before the separation of the cardiopulmonary bypass using a pharmacokinetic model, 1 mg of protamine for each 100 IU of residual heparin

Group Type: EXPERIMENTAL

Dosing according residual heparin

Intervention Type: DRUG

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

Interventions

Conventional dose

Conventional dose used to calculated the protamine dose

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universidad El Bosque, Bogotá

OTHER

Sponsor Role: collaborator

Fundación Clínica Shaio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mauricio Abello

Role: STUDY_CHAIR

Fundacion Abood Shaio

David Ramez

Role: PRINCIPAL_INVESTIGATOR

Universidad del bosque

Locations

Fundacion Abood Shaio

Bogotá, , Colombia

Site Status: RECRUITING

Countries

Colombia

Central Contacts

Fabian Cortez, MSc

Role: CONTACT

Phone: +57 (1) 593 8210

Email: fabian.cortes@shaio.org

Facility Contacts

Mauricio Abello

Role: primary

References

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.

Reference Type: BACKGROUND

PMID: 31576402 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28510738 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27493093 (View on PubMed)

Other Identifiers

DIB-20-34

Identifier Type: -

Identifier Source: org_study_id