Anticoagulant Antagonist ToxicityPhase 4SEPARATIONNCT04628884
Strategies for Protamine Dosing After Anticoagulation in Cardiovascular Surgery
A Phase 4 study testing Conventional dose and Dosing according residual heparin in people with Anticoagulant Antagonist Toxicity, run by Fundación Clínica Shaio at 1 site in Colombia.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anticoagulant Antagonist Toxicity
- What is being tested?
- Conventional dose and Dosing according residual heparin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 136 participants
- Where
- 1 siteColombia
- Study dates
- 15 Nov 2020to 22 Nov 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Colombia1 site, 1 recruiting
- Recruiting
Fundacion Abood Shaio
Bogotá
Mauricio Abello, +57 3103218780, mauricio.abello@shaio.org
David Ramirez
About this study
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
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
- Being tested
- Conventional dose, Dosing according residual heparin
- Keywords
- heparin, protamine, dose, extracorporeal circulation, cardiopulmonary bypass
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conventional doseDrug
Conventional dose used to calculated the protamine dose
Dosing according residual heparinDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Dosing according residual heparin |
What is being measured
The primary outcome is the main question the study is designed to answer.
postoperative mediastinal bleeding
total blood collected from the mediastinal chest tubes during the first 24 hours
Measured: first 24 hours after surgery
Secondary outcomes (1)
total blood products transfused
red blood cells, plasma, cryoprecipitate, platelets, fibrinogen, and prothrombin complexes
Measured: first 24 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2020
- Study start15 Nov 2020
- Primary completion20 Nov 2021 (estimated)
- Study completion22 Nov 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Anticoagulant Antagonist ToxicityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 136 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundación Clínica Shaio
- Sponsor type
- University, hospital or other
- Collaborators
- Universidad El Bosque, Bogotá
- Responsible party
- Sponsor
- Investigators
- Mauricio Abello, Study chair, Fundacion Abood ShaioDavid Ramez, Principal investigator, Universidad del bosque
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04628884
- Sponsor's protocol ID
- DIB-20-34
- Acronym
- SEPARATION
- Status last verified
- Nov 2020
- First submitted
- 9 Nov 2020
- Last updated
- 1 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31576402Delavenne 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.
PubMed 28510738Meesters 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.
PubMed 27493093
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04628884
- Acronym / sponsor ID
- SEPARATION / DIB-20-34
- Conditions
- Anticoagulant Antagonist Toxicity
- Keywords
- heparin, protamine, dose, extracorporeal circulation, cardiopulmonary bypass
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 136 participants (estimated)
- Lead sponsor
- Fundación Clínica ShaioUniversity, hospital or other
- Collaborators
- Universidad El Bosque, Bogotá
- Study start
- 15 Nov 2020 (actual)
- Primary completion
- 20 Nov 2021 (estimated)
- Study completion
- 22 Nov 2021 (estimated)
- First posted
- 16 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Protamine dosing according the total heparin administrated | Active comparator | Drug: Conventional doseThe 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 |
| Protamine dosing according the residual heparin determined by a pharmacokinetic model | Experimental | Drug: Dosing according residual heparinThe 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Conventional doseConventional dose used to calculated the protamine dose | Drug | Protamine dosing according the total heparin administrated |
| Dosing according residual heparinIn 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 | Drug | Protamine dosing according the residual heparin determined by a pharmacokinetic model |
Primary outcome
postoperative mediastinal bleeding
Time frame: first 24 hours after surgery
total blood collected from the mediastinal chest tubes during the first 24 hours
1 secondary outcome
total blood products transfused
Time frame: first 24 hours after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2020.
- Background: PubMed 31576402Puis 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.
- Background: PubMed 28510738Delavenne 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.
- Background: PubMed 27493093Meesters 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mauricio Abello study chair
Fundacion Abood Shaio
David Ramez principal investigator
Universidad del bosque
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Conventional dose and Dosing according residual heparin in people with Anticoagulant Antagonist Toxicity, run by Fundación Clínica Shaio at 1 site in Colombia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fabian Cortez, MSc (+57 (1) 593 8210, fabian.cortes@shaio.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
postoperative mediastinal bleeding (time frame: first 24 hours after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04628884, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2020.