Heparin ResistanceNCT07549568
Antithrombin as a Predictor of Heparin Resistance in Cardiac Surgery With Cardiopulmonary Bypass
An observational study of Heparin Resistance and Cardiac Surgery, run by Sahlgrenska University Hospital at 1 site in Sweden.
Trial summary
This study aims to investigate whether the level of antithrombin (AT) in the blood before cardiac surgery can predict how well patients respond to heparin, a medication used to prevent blood clotting during surgery with a heart-lung machine (cardiopulmonary bypass). Heparin requires antithrombin to work effectively. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heparin Resistance, Cardiac Surgery, Cardiopulmonary Bypass
- How many people
- 300 participants
- Where
- 1 siteSweden
- Study dates
- 1 Jun 2026to 1 May 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: Adult patients undergoing elective or sub-acute cardiac surgery with cardiopulmonary bypass at Sahlgrenska University Hospital, Sweden. Patients are consecutively included to reflect routine clinical practice and minimize selection bias.
Who may be able to join
- Age ≥18 years
- Planned cardiac surgery with cardiopulmonary bypass
- Ability to provide informed consent
Who cannot join
- Emergency cardiac surgery
- Ongoing antithrombin supplementation prior to surgery
- Known severe congenital coagulation disorder affecting interpretation of outcomes
- Severe liver failure
- Missing key data required to define heparin resistance (e.g., missing heparin dose or ACT values)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sweden1 site
Sahlgrenska University Hospital
Gothenburg, Västra Götalandsregionen, 41345
Anna Corderfeldt Keiller, PhD, +313427737, anna.corderfeldt@gu.se
Daniel Bengtsson, MSc, +313427730, daniel.bengtsson@vgregion.se
About this study
This study aims to investigate whether the level of antithrombin (AT) in the blood before cardiac surgery can predict how well patients respond to heparin, a medication used to prevent blood clotting during surgery with a heart-lung machine (cardiopulmonary bypass).
Heparin requires antithrombin to work effectively. Some patients have lower levels of antithrombin, which may result in reduced response to heparin, a condition known as heparin resistance. This can lead to difficulties achieving adequate anticoagulation during surgery and may require additional medication or adjustments in treatment.
Read more
In this study, an additional blood sample will be taken after anesthesia induction but before the administration of heparin. No changes will be made to the patient's treatment or care. Clinical data, including laboratory values, heparin dosing, and surgical outcomes, will be collected from routine medical records.
The goal is to identify a clinically useful antithrombin threshold that can help detect patients at risk of heparin resistance. This may improve patient safety, optimize treatment strategies, and reduce unnecessary use of antithrombin therapy in the future.
Read the detailed description
This prospective observational cohort study aims to evaluate whether preoperative antithrombin (AT) levels can predict heparin resistance in adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) at Sahlgrenska University Hospital, Sweden.
Heparin is routinely administered during CPB to prevent thrombus formation in the extracorporeal circuit. Its anticoagulant effect depends on the presence of antithrombin, a key endogenous inhibitor of coagulation. Reduced levels of antithrombin are known to impair the anticoagulant response to heparin and may result in heparin resistance. Clinically, this can lead to repeated heparin dosing, delays in achieving adequate anticoagulation, and increased use of antithrombin supplementation. However, there is currently no well-established threshold for antithrombin levels that can reliably identify patients at risk prior to heparin administration.
The study is designed as a non-interventional investigation in which all patients are managed according to standard clinical practice. A single additional blood sample for measurement of antithrombin will be obtained after induction of anesthesia and prior to administration of heparin. This timing is chosen to ensure standardized conditions and to minimize the influence of hemodilution and perioperative physiological changes.
Clinical and perioperative data will be collected from routine medical records, including anesthesia records, perfusion protocols, and laboratory systems. These data will be used to assess the relationship between preoperative antithrombin levels and the anticoagulant response to heparin during CPB, as well as associated perioperative outcomes.
The primary objective is to determine whether antithrombin levels can serve as a clinically useful predictor of heparin resistance. The analysis will focus on evaluating the discriminative ability of antithrombin and identifying a threshold value that may be useful for clinical decision-making. Secondary analyses will explore the association between antithrombin levels, heparin dosing requirements, and perioperative outcomes.
As an observational study, no changes are made to patient management. The study is expected to provide clinically relevant information that may support more individualized anticoagulation strategies and reduce unnecessary use of antithrombin supplementation in the future.
- Conditions
- Heparin Resistance, Cardiac Surgery, Cardiopulmonary Bypass
- Being tested
- No intervention (observational study)
- Keywords
- Antithrombin, Antithrombin III, Heparin resistance, Activated clotting time, ACT, Cardiopulmonary bypass, Cardiac surgery, Anticoagulation, Heparin response, Predictive biomarker
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No intervention (observational study)Other
This is a prospective observational study. No intervention is assigned as part of the study protocol. All patients receive standard clinical care. A preoperative blood sample is collected for measurement of antithrombin levels, and clinical data are recorded to assess the relationship between antithrombin levels and heparin resistance without influencing treatment.
| Study group | Role | What they receive |
|---|---|---|
| Patients undergoing cardiac surgery with cardiopulmonary bypass | Adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) at Sahlgrenska University Hospital, Sweden. All patients are managed according to standard clinical practice. A preoperative blood sample is collected to measure antithrombin levels, and clinical data are collected to assess the relationship between antithrombin levels and heparin resistance. No study-specific intervention is performed. Receives: Other: No intervention (observational study) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heparin resistance
Heparin resistance defined as failure to achieve an activated clotting time (ACT) ≥480 seconds after administration of an initial heparin dose of 350 IU/kg, according to standard clinical practice.
Measured: Intraoperative (immediately after initial heparin administration)
Secondary outcomes (3)
Activated clotting time after initial heparin dose
Activated clotting time (ACT) measured after administration of the initial heparin dose.
Measured: Intraoperative (after initial heparin administration)
Total heparin dose
Total cumulative heparin dose administered until activated clotting time (ACT) ≥480 seconds is achieved.
Measured: Intraoperative
Antithrombin supplementation
Administration of antithrombin concentrate due to insufficient anticoagulation.
Measured: Intraoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2026
- Study start1 Jun 2026 (estimated)
- Primary completion1 Oct 2027 (estimated)
- Study completion1 May 2028 (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 Heparin ResistanceStudies of the same condition, open and under way.
- More trials run by Sahlgrenska University HospitalThe 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
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sahlgrenska University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anna Corderfeldt Keiller, Sahlgrenska University Hospital
- Investigators
- Anna Corderfeldt Keiller, PhD, Principal investigator, Sahlgrenska University Hospital and University of Gothenburg, Department of Clinical Sciences, Gothenburg, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07549568
- Sponsor's protocol ID
- ANTITHROMBIN-HLM-2026
- Status last verified
- Apr 2026
- First submitted
- 16 Apr 2026
- Last updated
- 4 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying the results reported in this study (including demographic, clinical, laboratory, and perioperative variables) will be made available. Data will be stored and managed through DORIS, a secure research data repository at the University of Gothenburg, in accordance with Swedish data protection legislation and the General Data Protection Regulation (GDPR, EU 2016/679). Access to data will be provided upon reasonable request from qualified researchers, subject to ethical approval and data access agreements. A persistent digital object identifier (DOI) will be assigned to the dataset. Data access will be granted following review and approval of a methodologically sound research proposal, ensuring compliance with applicable legal and ethical requirements.
Publications
Chen Y, Phoon PHY, Hwang NC. Heparin Resistance During Cardiopulmonary Bypass in Adult Cardiac Surgery. J Cardiothorac Vasc Anesth. 2022 Nov;36(11):4150-4160. doi: 10.1053/j.jvca.2022.06.021. Epub 2022 Jun 24.
PubMed 35927191Levy JH, Sniecinski RM, Maier CL, Despotis GJ, Ghadimi K, Helms J, Ranucci M, Steiner ME, Tanaka KA, Connors JM. Finding a common definition of heparin resistance in adult cardiac surgery: communication from the ISTH SSC subcommittee on perioperative and critical care thrombosis and hemostasis. J Thromb Haemost. 2024 Apr;22(4):1249-1257. doi: 10.1016/j.jtha.2024.01.001. Epub 2024 Jan 11.
PubMed 38215912Rivera Jimenez KE, Mamani Ticona YM, Gutierrez-Chavez G, Astudillo CO, Calle E, Heredia GAT, Lopez Delgado DS, Rivera-Lozada O, Barboza JJ. Heparin Resistance in Cardiac Surgery with Cardiopulmonary Bypass: Mechanisms, Clinical Implications, and Evidence-Based Management. Medicina (Kaunas). 2025 Nov 23;61(12):2088. doi: 10.3390/medicina61122088.
PubMed 41470090
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antithrombin as a Predictor of Heparin Resistance in Cardiac Surgery With Cardiopulmonary Bypass
- ClinicalTrials.gov ID
- NCT07549568
- Acronym / sponsor ID
- ANTITHROMBIN-HLM-2026
- Conditions
- Heparin Resistance, Cardiac Surgery, Cardiopulmonary Bypass
- Keywords
- Antithrombin, Antithrombin III, Heparin resistance, Activated clotting time, ACT, Cardiopulmonary bypass, Cardiac surgery, Anticoagulation
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Sahlgrenska University HospitalUniversity, hospital or other
- Study start
- 1 Jun 2026 (estimated)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 May 2028 (estimated)
- First posted
- 24 Apr 2026 (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.
This study aims to investigate whether the level of antithrombin (AT) in the blood before cardiac surgery can predict how well patients respond to heparin, a medication used to prevent blood clotting during surgery with a heart-lung machine (cardiopulmonary bypass).
Heparin requires antithrombin to work effectively. Some patients have lower levels of antithrombin, which may result in reduced response to heparin, a condition known as heparin resistance. This can lead to difficulties achieving adequate anticoagulation during surgery and may require additional medication or adjustments in treatment.
In this study, an additional blood sample will be taken after anesthesia induction but before the administration of heparin. No changes will be made to the patient's treatment or care. Clinical data, including laboratory values, heparin dosing, and surgical outcomes, will be collected from routine medical records.
The goal is to identify a clinically useful antithrombin threshold that can help detect patients at risk of heparin resistance. This may improve patient safety, optimize treatment strategies, and reduce unnecessary use of antithrombin therapy in the future.
Detailed description
This prospective observational cohort study aims to evaluate whether preoperative antithrombin (AT) levels can predict heparin resistance in adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) at Sahlgrenska University Hospital, Sweden.
Heparin is routinely administered during CPB to prevent thrombus formation in the extracorporeal circuit. Its anticoagulant effect depends on the presence of antithrombin, a key endogenous inhibitor of coagulation. Reduced levels of antithrombin are known to impair the anticoagulant response to heparin and may result in heparin resistance. Clinically, this can lead to repeated heparin dosing, delays in achieving adequate anticoagulation, and increased use of antithrombin supplementation. However, there is currently no well-established threshold for antithrombin levels that can reliably identify patients at risk prior to heparin administration.
The study is designed as a non-interventional investigation in which all patients are managed according to standard clinical practice. A single additional blood sample for measurement of antithrombin will be obtained after induction of anesthesia and prior to administration of heparin. This timing is chosen to ensure standardized conditions and to minimize the influence of hemodilution and perioperative physiological changes.
Clinical and perioperative data will be collected from routine medical records, including anesthesia records, perfusion protocols, and laboratory systems. These data will be used to assess the relationship between preoperative antithrombin levels and the anticoagulant response to heparin during CPB, as well as associated perioperative outcomes.
The primary objective is to determine whether antithrombin levels can serve as a clinically useful predictor of heparin resistance. The analysis will focus on evaluating the discriminative ability of antithrombin and identifying a threshold value that may be useful for clinical decision-making. Secondary analyses will explore the association between antithrombin levels, heparin dosing requirements, and perioperative outcomes.
As an observational study, no changes are made to patient management. The study is expected to provide clinically relevant information that may support more individualized anticoagulation strategies and reduce unnecessary use of antithrombin supplementation in the future.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients undergoing cardiac surgery with cardiopulmonary bypass | – | Other: No intervention (observational study)Adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) at Sahlgrenska University Hospital, Sweden. All patients are managed according to standard clinical practice. A preoperative blood sample is collected to measure antithrombin levels, and clinical data are collected to assess the relationship between antithrombin levels and heparin resistance. No study-specific intervention is performed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients undergoing elective or sub-acute cardiac surgery with cardiopulmonary bypass at Sahlgrenska University Hospital, Sweden. Patients are consecutively included to reflect routine clinical practice and minimize selection bias.
Key inclusion criteria (3 listed)
- Age ≥18 years
- Planned cardiac surgery with cardiopulmonary bypass
- Ability to provide informed consent
Key exclusion criteria (5 listed)
- Emergency cardiac surgery
- Ongoing antithrombin supplementation prior to surgery
- Known severe congenital coagulation disorder affecting interpretation of outcomes
- Severe liver failure
- Missing key data required to define heparin resistance (e.g., missing heparin dose or ACT values)
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 |
|---|---|---|
| No intervention (observational study)This is a prospective observational study. No intervention is assigned as part of the study protocol. All patients receive standard clinical care. A preoperative blood sample is collected for measurement of antithrombin levels, and clinical data are recorded to assess the relationship between antithrombin levels and heparin resistance without influencing treatment. | Other | Patients undergoing cardiac surgery with cardiopulmonary bypass |
Primary outcome
Heparin resistance
Time frame: Intraoperative (immediately after initial heparin administration)
Heparin resistance defined as failure to achieve an activated clotting time (ACT) ≥480 seconds after administration of an initial heparin dose of 350 IU/kg, according to standard clinical practice.
3 secondary outcomes
Activated clotting time after initial heparin dose
Time frame: Intraoperative (after initial heparin administration)
Total heparin dose
Time frame: Intraoperative
Antithrombin supplementation
Time frame: Intraoperative
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2026.
- Background: PubMed 35927191Chen Y, Phoon PHY, Hwang NC. Heparin Resistance During Cardiopulmonary Bypass in Adult Cardiac Surgery. J Cardiothorac Vasc Anesth. 2022 Nov;36(11):4150-4160. doi: 10.1053/j.jvca.2022.06.021. Epub 2022 Jun 24.
- Background: PubMed 38215912Levy JH, Sniecinski RM, Maier CL, Despotis GJ, Ghadimi K, Helms J, Ranucci M, Steiner ME, Tanaka KA, Connors JM. Finding a common definition of heparin resistance in adult cardiac surgery: communication from the ISTH SSC subcommittee on perioperative and critical care thrombosis and hemostasis. J Thromb Haemost. 2024 Apr;22(4):1249-1257. doi: 10.1016/j.jtha.2024.01.001. Epub 2024 Jan 11.
- Background: PubMed 41470090Rivera Jimenez KE, Mamani Ticona YM, Gutierrez-Chavez G, Astudillo CO, Calle E, Heredia GAT, Lopez Delgado DS, Rivera-Lozada O, Barboza JJ. Heparin Resistance in Cardiac Surgery with Cardiopulmonary Bypass: Mechanisms, Clinical Implications, and Evidence-Based Management. Medicina (Kaunas). 2025 Nov 23;61(12):2088. doi: 10.3390/medicina61122088.
- Individual participant dataSharing planned: Yes. De-identified individual participant data underlying the results reported in this study (including demographic, clinical, laboratory, and perioperative variables) will be made available. Data will be stored and managed through DORIS, a secure research data repository at the University of Gothenburg, in accordance with Swedish data protection legislation and the General Data Protection Regulation (GDPR, EU 2016/679). Access to data will be provided upon reasonable request from qualified researchers, subject to ethical approval and data access agreements. A persistent digital object identifier (DOI) will be assigned to the dataset. Data access will be granted following review and approval of a methodologically sound research proposal, ensuring compliance with applicable legal and ethical requirements.
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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.
Anna Corderfeldt Keiller, PhD principal investigator
Sahlgrenska University Hospital and University of Gothenburg, Department of Clinical Sciences, Gothenburg, Sweden
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 Heparin Resistance and Cardiac Surgery, run by Sahlgrenska University Hospital at 1 site in Sweden.
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 3 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: opening soon, as of the sponsor's last update on 4 May 2026. 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 Sweden. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anna Corderfeldt Keiller, PhD (+46313427737, anna.corderfeldt@gu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heparin resistance (time frame: Intraoperative (immediately after initial heparin administration)). 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 NCT07549568, 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 4 May 2026.