Cardiac Surgery Requiring Extracorporeal CirculationPICSNCT04092868
Heparin Antagonization by Protamine in Cardiac Surgery: Pharmacokinetic/Pharmacodynamic Study
An observational study of Cardiac Surgery Requiring Extracorporeal Circulation, run by Centre Hospitalier Universitaire de Saint Etienne at 1 site in France.
Trial summary
Protamine is currently used during cardiac surgery to neutralize unfractionated heparin (UFH) at the end of extra-corporeal circulation (ECC). The optimal dose of protamine is currently unknown, and the administration of protamine is done empirically. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Surgery Requiring Extracorporeal Circulation
- What is being tested?
- Blood samples PK/ PD protamine
- Type of treatment
- Injection or infusion
- How many people
- 70 participants
- Where
- 1 siteFrance
- Study dates
- 13 Nov 2019to 12 Mar 2021
- Phase
- Observational
- 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
Study population: patients with cardiac surgery under CEC
Who may be able to join
- Patients benefiting from scheduled or emergency at the Saint-Etienne University Hospital (coronary artery bypass grafting, valve replacements, aortic dissections).
Who cannot join
- Patients with a contraindication to UFH
- Patients with a contraindication to protamine
- Patients requiring early resurgery.
- Patients receiving an injection of antithrombin III.
- Pregnant women.
- Patient for whom aprotinin use is planned during surgery.
Trial locations and contacts
1 site in 1 country.
About this study
Protamine is currently used during cardiac surgery to neutralize unfractionated heparin (UFH) at the end of extra-corporeal circulation (ECC). The optimal dose of protamine is currently unknown, and the administration of protamine is done empirically.
Protamine and UFH pharmacokinetics are characterized by a large inter-individual variability. A dose of protamine proportional to the amount of UFH administrated during the surgery may be therefore not adapted to most of the patients and exposed them to a risk of under or over dosage.
In this study, research investigators hypothesize that an accurate characterization of the pharmacokinetic/pharmacodynamic (PK/PD) relationship of protamine may help to optimize propose an optimal dosing regimen.
- Being tested
- Blood samples PK/ PD protamine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samples PK/ PD protamineOther
PK/ PD protamine
| Study group | Role | What they receive |
|---|---|---|
| cardiac surgery with extracorporeal circulation | during the operation
Intervention Blood sample :
- Choay Heparin (pharmacokinetic) concentration: t = 5, 15, 30 minutes after the start of the heparin injection + t = 5, 30, 60 minutes after the start of extracorporeal circulation
* protamine dosage: t = 2, 5, 8, 10 and 15 min after protamine injection
* anti-X activity t = 0 before administration and at time 2, 5, 8, 10 and 15 min then at time 1, 3, 5, 6 and 7 hours after protamine injection
* thrombin generation test (TGT) activity (thrombinography) : t = 2, 5, 8, 10 and 15 min after protamine injection Receives: Other: Blood samples PK/ PD protamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK/PD Protamine
Pharmacokinetics (PK) : plasma concentration of protamine measured by liquid chromatography coupled with mass spectrometry.
Pharmacodynamics (PD) :The effect of protamine corresponds to the kinetics of the disappearance of UFH in the blood. To do this, the investigators measure its concentration using an anti-Xa activity measurement technique.
Measured: 1 day
Secondary outcomes (3)
PK/PD Protamine
PK: evolution of protamine concentrations over time (plasma concentration of protamine measured by liquid chromatography coupled with mass spectrometry).
PD: ts neutralizing effect evaluated by thrombinography .
Measured: 1 day
postoperative blood loss:
quantities of blood loss in pleural and mediastinal drains during the first 24 hours postoperatively.
Measured: 1 day
ratios between the amount of UFH present at the protamine injection and the dose of protamine administered.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2019
- Study start13 Nov 2019
- Primary completion12 Mar 2021
- Study completion12 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiac Surgery Requiring Extracorporeal CirculationStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de Saint EtienneThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Julien LANOISELÉE, MD, Principal investigator, Centre Hospitalier Universitaire de Saint Etienne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04092868
- Sponsor's protocol ID
- 19CH046
- Other IDs
- 2019-000859-14, 2019
- Acronym
- PICS
- Status last verified
- Mar 2021
- First submitted
- 9 Sep 2019
- Last updated
- 26 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lanoiselee J, Gibert A, Gouin-Thibault I, Mansour A, Pontis A, Morizot C, Goset M, Molliex S, Morel J, Noyel P, Azarnoush K, Petrosyan A, Delavenne X, Zufferey PJ, Ollier E. Optimising protamine dosing for heparin reversal after cardiopulmonary bypass: a population pharmacokinetic-pharmacodynamic study. Br J Anaesth. 2026 Mar;136(3):847-855. doi: 10.1016/j.bja.2025.11.057. Epub 2026 Feb 4.
PubMed 41638976
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Heparin Antagonization by Protamine in Cardiac Surgery: Pharmacokinetic/Pharmacodynamic Study
- ClinicalTrials.gov ID
- NCT04092868
- Acronym / sponsor ID
- PICS / 19CH046
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de Saint EtienneUniversity, hospital or other
- Study start
- 13 Nov 2019 (actual)
- Primary completion
- 12 Mar 2021 (actual)
- Study completion
- 12 Mar 2021 (actual)
- First posted
- 17 Sep 2019 (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.
Protamine is currently used during cardiac surgery to neutralize unfractionated heparin (UFH) at the end of extra-corporeal circulation (ECC). The optimal dose of protamine is currently unknown, and the administration of protamine is done empirically.
Protamine and UFH pharmacokinetics are characterized by a large inter-individual variability. A dose of protamine proportional to the amount of UFH administrated during the surgery may be therefore not adapted to most of the patients and exposed them to a risk of under or over dosage.
In this study, research investigators hypothesize that an accurate characterization of the pharmacokinetic/pharmacodynamic (PK/PD) relationship of protamine may help to optimize propose an optimal dosing regimen.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| cardiac surgery with extracorporeal circulation | – | Other: Blood samples PK/ PD protamineduring the operation Intervention Blood sample : - Choay Heparin (pharmacokinetic) concentration: t = 5, 15, 30 minutes after the start of the heparin injection + t = 5, 30, 60 minutes after the start of extracorporeal circulation * protamine dosage: t = 2, 5, 8, 10 and 15 min after protamine injection * anti-X activity t = 0 before administration and at time 2, 5, 8, 10 and 15 min then at time 1, 3, 5, 6 and 7 hours after protamine injection * thrombin generation test (TGT) activity (thrombinography) : t = 2, 5, 8, 10 and 15 min after protamine injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients with cardiac surgery under CEC
Key inclusion criteria (1 listed)
- Patients benefiting from scheduled or emergency at the Saint-Etienne University Hospital (coronary artery bypass grafting, valve replacements, aortic dissections).
Key exclusion criteria (6 listed)
- Patients with a contraindication to UFH
- Patients with a contraindication to protamine
- Patients requiring early resurgery.
- Patients receiving an injection of antithrombin III.
- Pregnant women.
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 |
|---|---|---|
| Blood samples PK/ PD protaminePK/ PD protamine | Other | cardiac surgery with extracorporeal circulation |
Primary outcome
PK/PD Protamine
Time frame: 1 day
Pharmacokinetics (PK) : plasma concentration of protamine measured by liquid chromatography coupled with mass spectrometry. Pharmacodynamics (PD) :The effect of protamine corresponds to the kinetics of the disappearance of UFH in the blood. To do this, the investigators measure its concentration using an anti-Xa activity measurement technique.
3 secondary outcomes
PK/PD Protamine
Time frame: 1 day
postoperative blood loss:
Time frame: 1 day
ratios between the amount of UFH present at the protamine injection and the dose of protamine administered.
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2021.
- Derived from this study: PubMed 41638976Lanoiselee J, Gibert A, Gouin-Thibault I, Mansour A, Pontis A, Morizot C, Goset M, Molliex S, Morel J, Noyel P, Azarnoush K, Petrosyan A, Delavenne X, Zufferey PJ, Ollier E. Optimising protamine dosing for heparin reversal after cardiopulmonary bypass: a population pharmacokinetic-pharmacodynamic study. Br J Anaesth. 2026 Mar;136(3):847-855. doi: 10.1016/j.bja.2025.11.057. Epub 2026 Feb 4.
- 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.
Julien LANOISELÉE, MD principal investigator
Centre Hospitalier Universitaire de Saint Etienne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiac Surgery Requiring Extracorporeal Circulation, run by Centre Hospitalier Universitaire de Saint Etienne at 1 site in France.
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 1 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: finished, as of the sponsor's last update on 26 Mar 2021. 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 France. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PK/PD Protamine (time frame: 1 day). 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 NCT04092868, which also lists 1 linked publication.
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 26 Mar 2021.