Coagulation in Acute Aortic Dissection
- Conditions
- Coagulation DisorderAcute Aortic Dissection
- Interventions
- Procedure: Individualized HDR-approachProcedure: Conventional ACT-approach
- Registration Number
- NCT05484830
- Lead Sponsor
- Ivy susanne Modrau, MD
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 26
- Age > 18 years
- Emergent Acute Aortic Dissection with cardiopulmonary bypass
- Incapable of providing informed consent
- History of congenital coagulation disorder (haemophilia)
- Previous open cardiac surgery
- Death during induction of anaesthesia
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Individualised HDR-approach Individualized HDR-approach HMS Plus® Hemostasis Management System (Medtronic International, Tolochenaz, CH). Conventional ACT-approach Conventional ACT-approach ACT Hemostasis Management
- Primary Outcome Measures
Name Time Method F1+2 up to 2 days after surgery Prothrombin fragment 1+2 (pmol/L)
- Secondary Outcome Measures
Name Time Method PCC 24 hours after surgery Administration of prothrombin complex concentrate (Octaplex) (IU)
Resistance immediately after surgery Heparin resistance
Fibrinogen 24 hours after surgery Administration of fibrinogen concentrate (mg)
Cryoprecipitate Plasma 24 hours after surgery Administration of cryoprecipitate plasma
Recombinant FVIIa 24 hours after surgery Administration of Recombinant FVIIa
Reoperation for bleeding 30 days after surgery Reexploration for bleeding (yes/no)
Stroke 30 days after surgery Stroke (yes/no)
Length of surgery 30 days after surgery minutes
TAT up to 2 days after surgery Thrombin-Antithrombin Complex (ug/L)
Heparin (total) immediately after surgery Total amount of heparin
Blood cell-saver immediately after surgery Volume of blood processed in cell-saver (mL)
Drain output 48 hours after surgery Total mediastinal drain output (ml)
Protocol violation immediately after surgery Protocol violation (yes/no)
Length of stay ICU 30 days after surgery days
ETP up to 2 days after surgery Endogenous Thrombin Potential (nmol/L x min)
Antithrombin up to 2 days after surgery (kIU/L)
D-dimer up to 2 days after surgery D-dimer (mg/L)
2. Closure 30 days after surgery Secondary closure
Renal 30 days after surgery Requirement of continuous renal replacement therapy (yes/no)
Length of hospitalization 30 days after surgery Hospitalization (days)
Thrombin time up to 2 days after surgery High-dose thrombin time (sec)
Clot lysis up to 2 days after surgery Clot lysis
Heparin sensitivity prior to surgery Heparin sensitivity (slope)
Ratio immediately after surgery Protamin/heparin ratio
Blood loss sponges immediately after surgery Gravimetric estimation of intraoperative blood loss (calculation based on the change between dry and blood-soaked sponges, accounting for irrigation) in mL
Blood tranfusion 48 hours after surgery Tranfusion of blood products (units): Red blood cells, fresh frozen plasma, platelet concentrates
AT concentrate 24 hours after surgery Administration of Antithrombin concentrate (IU)
Protamin (total) immediately after surgery Total amount of protamin
Mortality up to 90 days after surgery All-cause mortality
Myocardial infarction 30 days after surgery Perioperative myocardial infarction (yes/no)
Low cardiac output syndrome 30 days after surgery Low cardiac output syndrome requiring inotropics or mechanical support (yes/no)
Vascular malperfusion 30 days after surgery Visceral og peripheral vascular malperfusion requiring surgical or percutaneous intervention
Intraop. coagulation Immediately after surgery Clinical signs of coagulation during CPB (yes/no)
Trial Locations
- Locations (1)
Aarhus University Hospital Skejby
🇩🇰Aarhus, Denmark