Coagulation in Acute Aortic Dissection

NCT05484830 | Completed DMC

• 1 other identifier: 1-10-72-30-22
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Aortic Dissection; Coagulation Disorder

Outcome Measures

Primary Outcomes (1)

• F1+2

  Prothrombin fragment 1+2 (pmol/L)

  up to 2 days after surgery

Secondary Outcomes (33)

• TAT

  up to 2 days after surgery

• ETP

  up to 2 days after surgery

• Thrombin time

  up to 2 days after surgery

• Antithrombin

  up to 2 days after surgery

• D-dimer

  up to 2 days after surgery

Study Arms (2)

Individualised HDR-approach

ACTIVE COMPARATOR

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

Procedure: Individualized HDR-approach

Conventional ACT-approach

ACTIVE COMPARATOR

ACT Hemostasis Management

Procedure: Conventional ACT-approach

Interventions

Individualized HDR-approach 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.

Individualised HDR-approach

Conventional ACT-approach 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.).

Conventional ACT-approach

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Ivy susanne Modrau, MD: lead

Study Sites (1)

Aarhus University Hospital Skejby

Aarhus, 8200, Denmark

Location

MeSH Terms

Conditions

Hemostatic Disorders

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Jens Eschen, Stud.med.

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

  PRINCIPAL INVESTIGATOR

• Ivy Modrau, MD, dr.med.

  University of Aarhus

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Treatment group allocation cannot be concealed for the operating team, but participants, other members of the treatment team, laboratory personnel and other practitioners administering postoperative care as well as outcome assessors will be blinded regarding the allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. Med., Consultant Cardiac Surgeon, Associate Professor

Model Details: Investigator-initiated single-site paralle-group (1:1) prospective, randomized, partially double-blinded trial

Study Record Dates

• First Submitted: May 26, 2022
• First Posted: August 2, 2022
• Study Start: November 1, 2022
• Primary Completion: September 17, 2024
• Study Completion: December 15, 2024
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)