Acute Aortic DissectionCAADNCT05484830
Coagulation in Acute Aortic Dissection
A study testing Individualized HDR-approach and Conventional ACT-approach in people with Acute Aortic Dissection and Coagulation Disorder, run by Ivy susanne Modrau, MD at 1 site in Denmark.
Trial summary
Acute aortic dissection (AAD) involving the ascending aorta (Stanford classification type A) remains a life-threatening disease. Excessive perioperative bleeding requiring massive transfusion of allogeneic blood products, and surgical reexploration remain major challenges in these patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Aortic Dissection, Coagulation Disorder
- What is being tested?
- Individualized HDR-approach and Conventional ACT-approach
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Nov 2022to 15 Dec 2024
- 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
- Age > 18 years
- Emergent Acute Aortic Dissection with cardiopulmonary bypass
- Incapable of providing informed consent
Who cannot join
- History of congenital coagulation disorder (haemophilia)
- Previous open cardiac surgery
- Death during induction of anaesthesia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Anticoagulation Management on Thrombin Generation During Surgery for Acute Aortic Dissection
Acute aortic dissection (AAD) involving the ascending aorta (Stanford classification type A) remains a life-threatening disease. Excessive perioperative bleeding requiring massive transfusion of allogeneic blood products, and surgical reexploration remain major challenges in these patients. Previous research has indicated that patients with AAD show pronounced haemostatic alterations prior to surgery which are aggravated during major aortic surgery with cardiopulmonary bypass and hypothermia full heparinization.
Intensified anticoagulation management guided by heparin dose response (HDR) calculation, and repeated measurement of heparin concentration may be more effective than standard empiric weight-based heparin and protamine management monitored by activated clotting time (ACT) measurements to suppress thrombin generation during surgery for AAD.
Read more
This randomized controlled clinical trial compares the impact of two recommended anticoagulation management strategies during surgery for AAD including deep hypothermia on activation of coagulation: Heparin/protamine-management based on HDR-titration by means of HMS Plus® versus current institutional standard (HDR- versus ACT-approach).
Primary endpoint is thrombin generation as measured by early postoperative prothrombin fragment 1+2 (F1+2). Secondary endpoints are other markers of coagulation and fibrinolysis as well as clinical outcome.
Read the detailed description
Hypotheses:
Primary: HDR-approach is superior to ACT-approach in terms of suppressing thrombin generation after emergent surgery for acute aortic dissection (Stanford type A).
Secondary: HDR-approach is superior with regard to
- early postoperative haemostatic capacity
- requirement of blood product transfusion and haemostatic agents
- postoperative bleeding
Design:
Investigator-initiated, single-site, parallel-group (1:1), prospective, randomized, partially double-blinded trial in patients undergoing emergent surgery for acute aortic dissection comparing two heparin management strategies with superiority design. Prior to randomization, patients are stratified according to preoperative organ dysfunction and anticoagulation therapy.
Acute research study design as patients with acute aortic dissection are considered incompetent according to the Danish Research Ethics Committees definition. Deferred consent by the competent patient or her/his proxy (next of kin) and an independent physician) is used. 26 consecutive patients undergoing emergent surgery for acute aortic dissection (Stanford type A) are randomized 1:1 into the following heparin management strategies with an ACT target of 480 seconds:
- Individualised HDR-approach
- Conventional ACT-approach
No interim analysis. A sub-study to compare cost-benefit of both strategies is planned.
- Conditions
- Acute Aortic Dissection, Coagulation Disorder
- Being tested
- Individualized HDR-approach, Conventional ACT-approach
- Medical subject headings
- Hemostatic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Individualized HDR-approachProcedure or surgery
Heparin concentration necessary to achieve target ACT > 480 sec. calculated based on individual HDR-curve.
If HDR slope ˂80 s/IU/mL (reduced sensitivity to heparin), 1000 IU of AT concentrate (Antitrombin III "Baxalta"®, Takeda Pharma, Vallensbæk Strand, DK). Whole blood concentration of circulating heparin assessed by heparin assays. Additional heparin given as required. After weaning, protamine necessary to reverse circulating heparin calculated according to heparin-protamine titration measurement. After protamine, heparin reversal evaluated with low-range heparin-protamine titration cartridge and additional protamine given as required.
Conventional ACT-approachProcedure or surgery
Initial Heparin 400 IU/kg (500 IU/kg if treated with heparin prior to surgery). ACT Assessment with Hemochron® Signature Elite (ITC, International Technidyne Corp., Edison, NJ, USA).
Additional heparin until ACT > 480 sec. If ACT < 480 sec. after despite repeated heparin supplement with 1000 IU of AT III concentrate. Target ACT > 480 sec. during normothermic CPB, and target ACT > 700 seconds during hypothermia After weaning, protamine 10mg/mL (0.7 mg of protamine/ 100 IU total heparin administered). Heparin reversal is evaluated with an activated partial thromboplastin (APTT). If APTT > 40 seconds, additional protamine (25-50 mg i.v.).
| Study group | Role | What they receive |
|---|---|---|
| Individualised HDR-approach | Active comparator | HMS Plus® Hemostasis Management System (Medtronic International, Tolochenaz, CH). Receives: Procedure: Individualized HDR-approach |
| Conventional ACT-approach | Active comparator | ACT Hemostasis Management Receives: Procedure: Conventional ACT-approach |
What is being measured
The primary outcome is the main question the study is designed to answer.
F1+2
Prothrombin fragment 1+2 (pmol/L)
Measured: up to 2 days after surgery
Secondary outcomes (33)
TAT
Thrombin-Antithrombin Complex (ug/L)
Measured: up to 2 days after surgery
ETP
Endogenous Thrombin Potential (nmol/L x min)
Measured: up to 2 days after surgery
Thrombin time
High-dose thrombin time (sec)
Measured: up to 2 days after surgery
Antithrombin
(kIU/L)
Measured: up to 2 days after surgery
D-dimer
D-dimer (mg/L)
Measured: up to 2 days after surgery
Clot lysis
Clot lysis
Measured: up to 2 days after surgery
Heparin sensitivity
Heparin sensitivity (slope)
Measured: prior to surgery
Heparin (total)
Total amount of heparin
Measured: immediately after surgery
Protamin (total)
Total amount of protamin
Measured: immediately after surgery
Ratio
Protamin/heparin ratio
Measured: immediately after surgery
Resistance
Heparin resistance
Measured: immediately after surgery
Blood cell-saver
Volume of blood processed in cell-saver (mL)
Measured: immediately after surgery
Blood loss sponges
Gravimetric estimation of intraoperative blood loss (calculation based on the change between dry and blood-soaked sponges, accounting for irrigation) in mL
Measured: immediately after surgery
Drain output
Total mediastinal drain output (ml)
Measured: 48 hours after surgery
Blood tranfusion
Tranfusion of blood products (units): Red blood cells, fresh frozen plasma, platelet concentrates
Measured: 48 hours after surgery
Fibrinogen
Administration of fibrinogen concentrate (mg)
Measured: 24 hours after surgery
PCC
Administration of prothrombin complex concentrate (Octaplex) (IU)
Measured: 24 hours after surgery
AT concentrate
Administration of Antithrombin concentrate (IU)
Measured: 24 hours after surgery
Cryoprecipitate Plasma
Administration of cryoprecipitate plasma
Measured: 24 hours after surgery
Recombinant FVIIa
Administration of Recombinant FVIIa
Measured: 24 hours after surgery
2. Closure
Secondary closure
Measured: 30 days after surgery
Reoperation for bleeding
Reexploration for bleeding (yes/no)
Measured: 30 days after surgery
Protocol violation
Protocol violation (yes/no)
Measured: immediately after surgery
Mortality
All-cause mortality
Measured: up to 90 days after surgery
Stroke
Stroke (yes/no)
Measured: 30 days after surgery
Myocardial infarction
Perioperative myocardial infarction (yes/no)
Measured: 30 days after surgery
Renal
Requirement of continuous renal replacement therapy (yes/no)
Measured: 30 days after surgery
Low cardiac output syndrome
Low cardiac output syndrome requiring inotropics or mechanical support (yes/no)
Measured: 30 days after surgery
Vascular malperfusion
Visceral og peripheral vascular malperfusion requiring surgical or percutaneous intervention
Measured: 30 days after surgery
Intraop. coagulation
Clinical signs of coagulation during CPB (yes/no)
Measured: Immediately after surgery
Length of surgery
minutes
Measured: 30 days after surgery
Length of stay ICU
days
Measured: 30 days after surgery
Length of hospitalization
Hospitalization (days)
Measured: 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2022
- Study start1 Nov 2022
- Primary completion17 Sep 2024
- Study completion15 Dec 2024
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 Acute Aortic DissectionStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Investigator-initiated single-site paralle-group (1:1) prospective, randomized, partially double-blinded trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ivy susanne Modrau, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ivy susanne Modrau, MD, Aarhus University Hospital Skejby
- Investigators
- Jens Eschen, Stud.med., Principal investigator, Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, DenmarkIvy Modrau, MD, dr.med., Study chair, University of Aarhus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05484830
- Sponsor's protocol ID
- 1-10-72-30-22
- Acronym
- CAAD
- Status last verified
- Jul 2025
- First submitted
- 26 May 2022
- Last updated
- 18 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Eschen JT, Larsen JB, Damsted AR, Kremke M, Nielsen PF, Tang M, Modrau IS. Heparin management and coagulation in acute aortic dissection surgery: a randomized controlled trial. J Thromb Haemost. 2026 Oct 5:S1538-7836(26)00626-4. doi: 10.1016/j.jtha.2026.09.036. Online ahead of print.
PubMed 42833295
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Anticoagulation Management on Thrombin Generation During Surgery for Acute Aortic Dissection
- ClinicalTrials.gov ID
- NCT05484830
- Acronym / sponsor ID
- CAAD / 1-10-72-30-22
- Conditions
- Acute Aortic Dissection, Coagulation Disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Ivy susanne Modrau, MDUniversity, hospital or other
- Study start
- 1 Nov 2022 (actual)
- Primary completion
- 17 Sep 2024 (actual)
- Study completion
- 15 Dec 2024 (actual)
- First posted
- 2 Aug 2022 (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.
Acute aortic dissection (AAD) involving the ascending aorta (Stanford classification type A) remains a life-threatening disease. Excessive perioperative bleeding requiring massive transfusion of allogeneic blood products, and surgical reexploration remain major challenges in these patients. Previous research has indicated that patients with AAD show pronounced haemostatic alterations prior to surgery which are aggravated during major aortic surgery with cardiopulmonary bypass and hypothermia full heparinization.
Intensified anticoagulation management guided by heparin dose response (HDR) calculation, and repeated measurement of heparin concentration may be more effective than standard empiric weight-based heparin and protamine management monitored by activated clotting time (ACT) measurements to suppress thrombin generation during surgery for AAD.
This randomized controlled clinical trial compares the impact of two recommended anticoagulation management strategies during surgery for AAD including deep hypothermia on activation of coagulation: Heparin/protamine-management based on HDR-titration by means of HMS Plus® versus current institutional standard (HDR- versus ACT-approach).
Primary endpoint is thrombin generation as measured by early postoperative prothrombin fragment 1+2 (F1+2). Secondary endpoints are other markers of coagulation and fibrinolysis as well as clinical outcome.
Detailed description
Hypotheses:
Primary: HDR-approach is superior to ACT-approach in terms of suppressing thrombin generation after emergent surgery for acute aortic dissection (Stanford type A).
Secondary: HDR-approach is superior with regard to
- early postoperative haemostatic capacity
- requirement of blood product transfusion and haemostatic agents
- postoperative bleeding
Design:
Investigator-initiated, single-site, parallel-group (1:1), prospective, randomized, partially double-blinded trial in patients undergoing emergent surgery for acute aortic dissection comparing two heparin management strategies with superiority design. Prior to randomization, patients are stratified according to preoperative organ dysfunction and anticoagulation therapy.
Acute research study design as patients with acute aortic dissection are considered incompetent according to the Danish Research Ethics Committees definition. Deferred consent by the competent patient or her/his proxy (next of kin) and an independent physician) is used. 26 consecutive patients undergoing emergent surgery for acute aortic dissection (Stanford type A) are randomized 1:1 into the following heparin management strategies with an ACT target of 480 seconds:
- Individualised HDR-approach
- Conventional ACT-approach
No interim analysis. A sub-study to compare cost-benefit of both strategies is planned.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- Investigator-initiated single-site paralle-group (1:1) prospective, randomized, partially double-blinded trial
| Arm | Type | Receives |
|---|---|---|
| Individualised HDR-approach | Active comparator | Procedure: Individualized HDR-approachHMS Plus® Hemostasis Management System (Medtronic International, Tolochenaz, CH). |
| Conventional ACT-approach | Active comparator | Procedure: Conventional ACT-approachACT Hemostasis Management |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age > 18 years
- Emergent Acute Aortic Dissection with cardiopulmonary bypass
- Incapable of providing informed consent
Key exclusion criteria (3 listed)
- History of congenital coagulation disorder (haemophilia)
- Previous open cardiac surgery
- Death during induction of anaesthesia
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 |
|---|---|---|
| Individualized HDR-approachHeparin concentration necessary to achieve target ACT > 480 sec. calculated based on individual HDR-curve. If HDR slope ˂80 s/IU/mL (reduced sensitivity to heparin), 1000 IU of AT concentrate (Antitrombin III "Baxalta"®, Takeda Pharma, Vallensbæk Strand, DK). Whole blood concentration of circulating heparin assessed by heparin assays. Additional heparin given as required. After weaning, protamine necessary to reverse circulating heparin calculated according to heparin-protamine titration measurement. After protamine, heparin reversal evaluated with low-range heparin-protamine titration cartridge and additional protamine given as required. | Procedure or surgery | Individualised HDR-approach |
| Conventional ACT-approachInitial Heparin 400 IU/kg (500 IU/kg if treated with heparin prior to surgery). ACT Assessment with Hemochron® Signature Elite (ITC, International Technidyne Corp., Edison, NJ, USA). Additional heparin until ACT > 480 sec. If ACT < 480 sec. after despite repeated heparin supplement with 1000 IU of AT III concentrate. Target ACT > 480 sec. during normothermic CPB, and target ACT > 700 seconds during hypothermia After weaning, protamine 10mg/mL (0.7 mg of protamine/ 100 IU total heparin administered). Heparin reversal is evaluated with an activated partial thromboplastin (APTT). If APTT > 40 seconds, additional protamine (25-50 mg i.v.). | Procedure or surgery | Conventional ACT-approach |
Primary outcome
F1+2
Time frame: up to 2 days after surgery
Prothrombin fragment 1+2 (pmol/L)
33 secondary outcomes
TAT
Time frame: up to 2 days after surgery
ETP
Time frame: up to 2 days after surgery
Thrombin time
Time frame: up to 2 days after surgery
Antithrombin
Time frame: up to 2 days after surgery
D-dimer
Time frame: up to 2 days after surgery
Clot lysis
Time frame: up to 2 days after surgery
Heparin sensitivity
Time frame: prior to surgery
Heparin (total)
Time frame: immediately after surgery
Protamin (total)
Time frame: immediately after surgery
Ratio
Time frame: immediately after surgery
Resistance
Time frame: immediately after surgery
Blood cell-saver
Time frame: immediately after surgery
Blood loss sponges
Time frame: immediately after surgery
Drain output
Time frame: 48 hours after surgery
Blood tranfusion
Time frame: 48 hours after surgery
Fibrinogen
Time frame: 24 hours after surgery
PCC
Time frame: 24 hours after surgery
AT concentrate
Time frame: 24 hours after surgery
Cryoprecipitate Plasma
Time frame: 24 hours after surgery
Recombinant FVIIa
Time frame: 24 hours after surgery
2. Closure
Time frame: 30 days after surgery
Reoperation for bleeding
Time frame: 30 days after surgery
Protocol violation
Time frame: immediately after surgery
Mortality
Time frame: up to 90 days after surgery
Stroke
Time frame: 30 days after surgery
Myocardial infarction
Time frame: 30 days after surgery
Renal
Time frame: 30 days after surgery
Low cardiac output syndrome
Time frame: 30 days after surgery
Vascular malperfusion
Time frame: 30 days after surgery
Intraop. coagulation
Time frame: Immediately after surgery
Length of surgery
Time frame: 30 days after surgery
Length of stay ICU
Time frame: 30 days after surgery
Length of hospitalization
Time frame: 30 days after surgery
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 18 Jul 2025.
- Derived from this study: PubMed 42833295Eschen JT, Larsen JB, Damsted AR, Kremke M, Nielsen PF, Tang M, Modrau IS. Heparin management and coagulation in acute aortic dissection surgery: a randomized controlled trial. J Thromb Haemost. 2026 Oct 5:S1538-7836(26)00626-4. doi: 10.1016/j.jtha.2026.09.036. Online ahead of print.
- Individual participant dataSharing planned: No
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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.
Jens Eschen, Stud.med. principal investigator
Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Denmark
Ivy Modrau, MD, dr.med. study chair
University of Aarhus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Individualized HDR-approach and Conventional ACT-approach in people with Acute Aortic Dissection and Coagulation Disorder, run by Ivy susanne Modrau, MD at 1 site in Denmark.
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 3 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 18 Jul 2025. 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 Denmark. 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?
F1+2 (time frame: up to 2 days 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 NCT05484830, 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 18 Jul 2025.