Cardiac Surgery With Cardiopulmonary BypassHARTNCT03787641
Systematic Evaluation of Protamine Doze in Cardiac Surgery
A study testing Protamine Sulfate in people with Cardiac Surgery With Cardiopulmonary Bypass, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial summary
The precise amount of protamine required to neutralize unfractionated heparin (UFH) remains unknown. This study will systematically identify the doze needed to neutralize UFH following cardiopulmonary bypass (CPB). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Surgery With Cardiopulmonary Bypass
- What is being tested?
- Protamine Sulfate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteCanada
- Study dates
- 20 Sep 2018to 28 Feb 2020
- Phase
- Interventional
- 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
- Elective cardiac surgery patients > 18 years age who can provide written consent for the study.
Who cannot join
- History of any known coagulopathies, liver dysfunction, previous cardiac surgery, preoperative abnormal coagulation profiles, recent exposure to heparin (unfractionated or low molecular weight), warfarin, clopidogrel or other direct thrombin inhibitors in the preceding 7 days.
- History of heparin resistance
- History of adverse reactions to protamine
- Patients identified as having heparin resistance
- Anticipated CPB time > 2-2.5 hrs
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
London Health Sciences Centre
London, Ontario, N6A 5A5
Ravi Taneja, FRCPC, 5196858500, Ravi.Taneja@lhsc.on.ca
About this study
Official title: Sysytematic Evaluation of Heparin and Protamine in Cardiac Surgery
The precise amount of protamine required to neutralize unfractionated heparin (UFH) remains unknown. This study will systematically identify the doze needed to neutralize UFH following cardiopulmonary bypass (CPB).
Read the detailed description
The precise dose of protamine needed to neutralize unfractionated heparin (UFH) is unknown. Research suggests that low dose protamine is associated with decreased need for transfusions in cardiac surgery. The ATS guidelines recommend that half of the total UFH dose given for cardiopulmonary bypass (CPB) should be neutralized with protamine. However, it is unknown if this is routinely followed by anesthesiologists. Furthermore, the reference standard for UFH has changed recently and it is unknown how this has affected the dose of protamine in the perioperative period. Protamine does have a very short life and heparin rebound occurs very commonly.
It is common practice to divert the suctioned mediastinal blood following CPB while the patient is still anticoagulated. The traditional practice is that once half dose protamine has been given, suction to the cardiotomy reservoir is turned off. All surgical field blood loss is then diverted to wall suction. The inherent risk of letting too much protamine into the CPB reservoir is that UFH therein may get neutralized and predispose to clot formation in the venous reservoir. This precludes an emergency 'crash' on to CPB, should that be required for some reason. Experience of the Investigators indicates that most surgeons will turn off suction leading to the cardiotomy reservoir once half the total protamine dose has been administered. The concern with this is that "half dose" protamine may be quite different for different anesthesiologists.
The research investigators hypothesize low dose protamine is sufficient to neutralize the effects of UFH as monitored through activated clotting time (ACT). Anesthesiologists administer varying doses of protamine to neutralize UFH in cardiac surgery and the rationale behind such decisions is unclear.
Thus, the primary objective of this study is to evaluate the dose of protamine required to neutralize UFH following CPB. Secondary objectives are 1) to assess the amount of protamine needed to neutralize UFH in intravenously administered cardiotomy reservoir blood. 2) To examine the amount of residual heparin postoperatively in the cardiac surgery ICU; 3) to examine, through semi-structured interviews, the decision-making processes involved in managing (anti)coagulation in cardiac surgery.
- Being tested
- Protamine Sulfate
- Keywords
- cardiopulmonary bypass, heparin, protamine, anti-IIa assay, anti-Xa assay, activated clotting time
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protamine SulfateDrug
Protamine Sulfate will be administered via an infusion pump to administer a 50 mg test doze, then 100 mg after 5 min waiting period. Following blood samples, additional alliquots of 50 mg will be measured to a maximum of 300 mg.
| Study group | Role | What they receive |
|---|---|---|
| Protamine doze | Other | Protamine Sulfate will be administered through an infusion pump in aliquots at a predefined rate (25 mg/min). Blood samples will be withdrawn after each aliquot and quantified for anti-Xa, IIa and ACT. Receives: Drug: Protamine Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in heparin activity
The functional activity is ideally measured via its ability to accelerate the inhibition of activated coagulation enzymes IIa (thrombin) and Xa respectively.
These tests are available commercially as ELISA kits. Briefly, an excess of coagulation factor IIa or Xa respectively is added to the sample and residual anti-IIa/Xa activity is quantified with a synthetic chromogenic substrate.
Measured: Duriing surgery (at baseline, before and after protamine adminitration following cardiopulmonary bypass). Samples will also be quantified at Intensive Care Unit (ICU) admission and 4 hours following ICU admission.
Change in Activated Clotting time (ACT)
ACT is the standard point of care test used in cardiac surgery. Blood is added to a tube containing predefined amount of coagulation accelerator (available commercially) and heparin activity is measured by prolongation or neutralization of ACT
Measured: Duriing surgery (at baseline, before and after protamine adminitration following cardiopulmonary bypass).
Secondary outcomes (1)
Rationale for choosing a certain doze of protamine
Anesthesiologists will undergo semi-structured face to face interviews and asked their rationale for choosing a certain doze of protamine
Measured: During surgery. (Average cardiac surgery lasts for 4-6 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2018
- Study start20 Sep 2018
- Primary completion31 Dec 2019 (estimated)
- Study completion28 Feb 2020 (estimated)
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 With Cardiopulmonary BypassStudies of the same condition, open and under way.
- More trials run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ravi Taneja, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03787641
- Sponsor's protocol ID
- 107681
- Acronym
- HART
- Status last verified
- Dec 2018
- First submitted
- 13 May 2016
- Last updated
- 31 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Taneja R, Szoke DJ, Hynes Z, Jones PM. Minimum protamine dose required to neutralize heparin in cardiac surgery: a single-centre, prospective, observational cohort study. Can J Anaesth. 2023 Feb;70(2):219-227. doi: 10.1007/s12630-022-02364-4. Epub 2022 Dec 5.
PubMed 36471142
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sysytematic Evaluation of Heparin and Protamine in Cardiac Surgery
- ClinicalTrials.gov ID
- NCT03787641
- Acronym / sponsor ID
- HART / 107681
- Keywords
- cardiopulmonary bypass, heparin, protamine, anti-IIa assay, anti-Xa assay, activated clotting time
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- 20 Sep 2018 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 28 Feb 2020 (estimated)
- First posted
- 26 Dec 2018 (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.
The precise amount of protamine required to neutralize unfractionated heparin (UFH) remains unknown. This study will systematically identify the doze needed to neutralize UFH following cardiopulmonary bypass (CPB).
Detailed description
The precise dose of protamine needed to neutralize unfractionated heparin (UFH) is unknown. Research suggests that low dose protamine is associated with decreased need for transfusions in cardiac surgery. The ATS guidelines recommend that half of the total UFH dose given for cardiopulmonary bypass (CPB) should be neutralized with protamine. However, it is unknown if this is routinely followed by anesthesiologists. Furthermore, the reference standard for UFH has changed recently and it is unknown how this has affected the dose of protamine in the perioperative period. Protamine does have a very short life and heparin rebound occurs very commonly.
It is common practice to divert the suctioned mediastinal blood following CPB while the patient is still anticoagulated. The traditional practice is that once half dose protamine has been given, suction to the cardiotomy reservoir is turned off. All surgical field blood loss is then diverted to wall suction. The inherent risk of letting too much protamine into the CPB reservoir is that UFH therein may get neutralized and predispose to clot formation in the venous reservoir. This precludes an emergency 'crash' on to CPB, should that be required for some reason. Experience of the Investigators indicates that most surgeons will turn off suction leading to the cardiotomy reservoir once half the total protamine dose has been administered. The concern with this is that "half dose" protamine may be quite different for different anesthesiologists.
The research investigators hypothesize low dose protamine is sufficient to neutralize the effects of UFH as monitored through activated clotting time (ACT). Anesthesiologists administer varying doses of protamine to neutralize UFH in cardiac surgery and the rationale behind such decisions is unclear.
Thus, the primary objective of this study is to evaluate the dose of protamine required to neutralize UFH following CPB. Secondary objectives are 1) to assess the amount of protamine needed to neutralize UFH in intravenously administered cardiotomy reservoir blood. 2) To examine the amount of residual heparin postoperatively in the cardiac surgery ICU; 3) to examine, through semi-structured interviews, the decision-making processes involved in managing (anti)coagulation in cardiac surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Protamine doze | Other | Drug: Protamine SulfateProtamine Sulfate will be administered through an infusion pump in aliquots at a predefined rate (25 mg/min). Blood samples will be withdrawn after each aliquot and quantified for anti-Xa, IIa and ACT. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Elective cardiac surgery patients > 18 years age who can provide written consent for the study.
Key exclusion criteria (5 listed)
- History of any known coagulopathies, liver dysfunction, previous cardiac surgery, preoperative abnormal coagulation profiles, recent exposure to heparin (unfractionated or low molecular weight), warfarin, clopidogrel or other direct thrombin inhibitors in the preceding 7 days.
- History of heparin resistance
- History of adverse reactions to protamine
- Patients identified as having heparin resistance
- Anticipated CPB time > 2-2.5 hrs
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 |
|---|---|---|
| Protamine SulfateProtamine Sulfate will be administered via an infusion pump to administer a 50 mg test doze, then 100 mg after 5 min waiting period. Following blood samples, additional alliquots of 50 mg will be measured to a maximum of 300 mg. | Drug | Protamine doze |
Primary outcome
Change in heparin activity
Time frame: Duriing surgery (at baseline, before and after protamine adminitration following cardiopulmonary bypass). Samples will also be quantified at Intensive Care Unit (ICU) admission and 4 hours following ICU admission.
The functional activity is ideally measured via its ability to accelerate the inhibition of activated coagulation enzymes IIa (thrombin) and Xa respectively. These tests are available commercially as ELISA kits. Briefly, an excess of coagulation factor IIa or Xa respectively is added to the sample and residual anti-IIa/Xa activity is quantified with a synthetic chromogenic substrate.
Change in Activated Clotting time (ACT)
Time frame: Duriing surgery (at baseline, before and after protamine adminitration following cardiopulmonary bypass).
ACT is the standard point of care test used in cardiac surgery. Blood is added to a tube containing predefined amount of coagulation accelerator (available commercially) and heparin activity is measured by prolongation or neutralization of ACT
1 secondary outcome
Rationale for choosing a certain doze of protamine
Time frame: During surgery. (Average cardiac surgery lasts for 4-6 hours)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2018.
- Derived from this study: PubMed 36471142Taneja R, Szoke DJ, Hynes Z, Jones PM. Minimum protamine dose required to neutralize heparin in cardiac surgery: a single-centre, prospective, observational cohort study. Can J Anaesth. 2023 Feb;70(2):219-227. doi: 10.1007/s12630-022-02364-4. Epub 2022 Dec 5.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Protamine Sulfate in people with Cardiac Surgery With Cardiopulmonary Bypass, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
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 5 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 31 Dec 2018. 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 Canada. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ravi Taneja, FRCPC (5196858500, Ravi.Taneja@lhsc.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in heparin activity (time frame: Duriing surgery (at baseline, before and after protamine adminitration following cardiopulmonary bypass). Samples will also be quantified at Intensive Care Unit (ICU) admission and 4 hours following ICU admission.). The study lists 2 primary outcomes in all. 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 NCT03787641, 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 31 Dec 2018.