Clinical trial NCT05484830: Coagulation in Acute Aortic Dissection
Official title: Impact of Anticoagulation Management on Thrombin Generation During Surgery for Acute Aortic Dissection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Acute Aortic Dissection
Coagulation Disorder
Lead sponsor: Aarhus University Hospital Skejby
Sponsor class: OTHER
First posted: 2022-08-02
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Investigator-initiated single-site paralle-group (1:1) prospective, randomized, partially double-blinded trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: F1+2
timeFrame: up to 2 days after surgery
Secondary outcomes:
measure: TAT
timeFrame: up to 2 days after surgery
measure: ETP
timeFrame: up to 2 days after surgery
measure: Thrombin time
timeFrame: up to 2 days after surgery
measure: Antithrombin
timeFrame: up to 2 days after surgery
measure: D-dimer
timeFrame: up to 2 days after surgery
measure: Clot lysis
timeFrame: up to 2 days after surgery
measure: Heparin sensitivity
timeFrame: prior to surgery
measure: Heparin (total)
timeFrame: immediately after surgery
measure: Protamin (total)
timeFrame: immediately after surgery
measure: Ratio
timeFrame: immediately after surgery
measure: Resistance
timeFrame: immediately after surgery
measure: Blood cell-saver
timeFrame: immediately after surgery
measure: Blood loss sponges
timeFrame: immediately after surgery
measure: Drain output
timeFrame: 48 hours after surgery
measure: Blood tranfusion
timeFrame: 48 hours after surgery
measure: Fibrinogen
timeFrame: 24 hours after surgery
measure: PCC
timeFrame: 24 hours after surgery
measure: AT concentrate
timeFrame: 24 hours after surgery
measure: Cryoprecipitate Plasma
timeFrame: 24 hours after surgery
measure: Recombinant FVIIa
timeFrame: 24 hours after surgery
measure: 2. Closure
timeFrame: 30 days after surgery
measure: Reoperation for bleeding
timeFrame: 30 days after surgery
measure: Protocol violation
timeFrame: immediately after surgery
measure: Mortality
timeFrame: up to 90 days after surgery
measure: Stroke
timeFrame: 30 days after surgery
measure: Myocardial infarction
timeFrame: 30 days after surgery
measure: Renal
timeFrame: 30 days after surgery
measure: Low cardiac output syndrome
timeFrame: 30 days after surgery
measure: Vascular malperfusion
timeFrame: 30 days after surgery
measure: Intraop. coagulation
timeFrame: Immediately after surgery
measure: Length of surgery
timeFrame: 30 days after surgery
measure: Length of stay ICU
timeFrame: 30 days after surgery
measure: Length of hospitalization
timeFrame: 30 days after surgery
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital Skejby
Study officials:
affiliation: Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Denmark
name: Jens Eschen, Stud.med.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Aarhus
name: Ivy Modrau, MD, dr.med.
role: STUDY_CHAIR
References: