Strategies for Protamine Dosing After Anticoagulation in Cardiovascular Surgery

NCT04628884 | Unknown Phase 4 DMC FDA Drug

• 1 other identifier: DIB-20-34
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• postoperative mediastinal bleeding

  total blood collected from the mediastinal chest tubes during the first 24 hours

  first 24 hours after surgery

Secondary Outcomes (1)

• total blood products transfused

  first 24 hours after surgery

Study Arms (2)

Protamine dosing according the total heparin administrated

ACTIVE COMPARATOR

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

Drug: Conventional dose

Protamine dosing according the residual heparin determined by a pharmacokinetic model

EXPERIMENTAL

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

Drug: Dosing according residual heparin

Interventions

Conventional dose DRUG

Conventional dose used to calculated the protamine dose

Protamine dosing according the total heparin administrated

Dosing according residual heparin 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

Protamine dosing according the residual heparin determined by a pharmacokinetic model

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundación Clínica Shaio: lead
• Universidad El Bosque, Bogotá: collaborator

Study Sites (1)

Fundacion Abood Shaio

Bogotá, Colombia

RECRUITING

Related Publications (3)

• 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.

  PMID: 31576402 BACKGROUND

• 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.

  PMID: 28510738 BACKGROUND

• 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.

  PMID: 27493093 BACKGROUND

Study Officials

• Mauricio Abello

  Fundacion Abood Shaio

  STUDY CHAIR

• David Ramez

  Universidad del bosque

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabian Cortez, MSc

CONTACT

+57 (1) 593 8210; fabian.cortes@shaio.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2020
• First Posted: November 16, 2020
• Study Start: November 15, 2020
• Primary Completion: November 20, 2021
• Study Completion: November 22, 2021
• Last Updated: December 1, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CO (1)