Coagulation in Acute Aortic Dissection

NCT ID: NCT05484830

Last Updated: 2025-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2024-12-15

Brief 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. 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.

Conditions

Acute Aortic Dissection; Coagulation Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Individualised HDR-approach

HMS Plus® Hemostasis Management System (Medtronic International, Tolochenaz, CH).

Group Type: ACTIVE_COMPARATOR

Individualized HDR-approach

Intervention Type: PROCEDURE

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-approach

ACT Hemostasis Management

Group Type: ACTIVE_COMPARATOR

Conventional ACT-approach

Intervention Type: PROCEDURE

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.).

Interventions

Individualized HDR-approach

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.

Intervention Type: PROCEDURE

Conventional ACT-approach

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.).

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age > 18 years
• Emergent Acute Aortic Dissection with cardiopulmonary bypass
• Incapable of providing informed consent

Exclusion Criteria

• History of congenital coagulation disorder (haemophilia)
• Previous open cardiac surgery
• Death during induction of anaesthesia

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ivy susanne Modrau, MD

OTHER

Sponsor Role: lead

Responsible Party

Ivy susanne Modrau, MD

Dr. Med., Consultant Cardiac Surgeon, Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jens Eschen, Stud.med.

Role: PRINCIPAL_INVESTIGATOR

Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Denmark

Ivy Modrau, MD, dr.med.

Role: STUDY_CHAIR

University of Aarhus

Locations

Aarhus University Hospital Skejby

Aarhus, , Denmark

Countries

Denmark

Other Identifiers

1-10-72-30-22

Identifier Type: -

Identifier Source: org_study_id