Coagulation in Acute Aortic Dissection (CAAD)

Ivy susanne Modrau, MD

Status: Completed

Conditions: Acute Aortic Dissection; Coagulation Disorder

Treatments: Procedure: Individualized HDR-approach; Procedure: Conventional ACT-approach

Study type: Interventional

Funder types: Other

Identifiers

NCT05484830

1-10-72-30-22

Details and patient eligibility

About

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.

Full 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.

Enrollment: 26 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

26 participants in 2 patient groups

Individualised HDR-approach

Active Comparator group

Description:

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

Treatment:

Procedure: Individualized HDR-approach

Conventional ACT-approach

Active Comparator group

Description:

ACT Hemostasis Management

Treatment:

Procedure: Conventional ACT-approach