Strategies for Protamine Dosing After Anticoagulation in Cardiovascular Surgery (SEPARATION)

November 28, 2020 updated by: Fundación Clínica Shaio

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
136

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Colombia
      • Bogotá, Colombia
        • Recruiting
        • Fundacion Abood Shaio
        • Contact:
        • Principal Investigator:
          • David Ramirez

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: 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
Drug: Conventional dose
Conventional dose used to calculated the protamine dose
EXPERIMENTAL: 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
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
postoperative mediastinal bleeding
Time Frame: first 24 hours after surgery
total blood collected from the mediastinal chest tubes during the first 24 hours
first 24 hours after surgery

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
total blood products transfused
Time Frame: first 24 hours after surgery
red blood cells, plasma, cryoprecipitate, platelets, fibrinogen, and prothrombin complexes
first 24 hours after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fundación Clínica Shaio

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Universidad El Bosque, Bogotá

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Mauricio Abello, Fundacion Abood Shaio
  • Principal Investigator: David Ramez, Universidad del bosque

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 15, 2020

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 20, 2021

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 22, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 9, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 9, 2020

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 16, 2020

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 1, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 28, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DIB-20-34

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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