Clinical trial NCT03649594: Risk Stratification Post TAVI Using TEG
Official title: Risk Stratification for Subclinical Leaflet Thrombosis Post TAVI Using Thromboelastography
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Platelet Function Tests
Predictive Value of Tests
Thrombelastography
Cardiovascular Diseases
Aortic Valve Stenosis
Thrombosis
Transcatheter Aortic Valve Replacement
Lead sponsor: University Hospital Freiburg
Sponsor class: OTHER
First posted: 2018-08-28
Enrollment: 100
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All patients that are scheduled for TAVI using a commercially available valve after clinical decision making within the local Heart Team will be possible subjects yielding the eligibility criteria.

Brief summary: Transcatheter aortic valve implantation (TAVI) has become the standard of care in elderly patients at increased risk for surgical aortic valve replacement . However, the optimal antithrombotic strategy post TAVI is still unclear. Current European guidelines recommend dual antiplatelet therapy (DAPT) for 3 to 6 months.The prevalence of subclinical leaflet thrombosis after TAVI is 15% up to 40%, but its clinical long-term relevance is uncertain. Thromboelastography (TEG(R)) can be used as a point-of-care system evaluating a patient's individual hemostasis profile. For the detection of transcatheter valve thrombosis it may be superior to conventional platelet function testing because global hemostasis can be assessed in addition to platelet function. The investigators intend an observational trial recruiting patients undergoing TAVI under standard care. At defined time points the investigators will serially perform TEG(R) as well as further platelet function testing (multiple electrode aggregometry) and conventional coagulation testing. The primary objective is to find surrogate TEG-derived markers / models predicting the development of a subclinical leaflet thrombosis after TAVI under usual care. The secondary objective is to find TEG-derived markers / models identifying patients at an increased risk after TAVI (all-cause mortality, cardiovascular mortality, thromboembolic and bleeding events).

Detailed description: Aortic stenosis is the most common primary valve disease in high-income countries with increasing importance. Throughout the last 15 years, transcatheter aortic valve implantation (TAVI) has become an alternative to surgical aortic valve replacement, the former standard of care. Nowadays, the use of TAVI in elderly patients at increased surgical risk is favored. There is still an important lack of evidence concerning the optimal antithrombotic strategy post TAVI. Recently, it has been shown that the prevalence of subclinical leaflet thrombosis after intervention has been underestimated and may be present in around 15 % up to 40% (PORTICO IDE trial) of transcatheter valves. One study demonstrated that transient ischemic attacks are significantly increased in these patients.

European guidelines are undecided towards the length of the dual antiplatelet therapy (DAPT) after TAVI and recommend optional treatment durations between 3 to 6 months. The optimal duration of DAPT is not known, although DAPT duration is associated with an increased bleeding risk. The most recent update of AHA guidelines for valvular heart disease state that oral anticoagulation with a VKA (INR of 2.5) may be reasonable for at least 3 months after TAVI in patients at low risk of bleeding. Without favoring one over the other recommendation, the current AHA guidelines also maintain the prior statement (from 2014) that clopidogrel 75 mg daily may be reasonable for the first 6 months after TAVI in addition to life-long aspirin, which is in accordance with the European Guideline recommendation. On the other hand, the GALILEO trial has recently been stopped as patients receiving rivaroxaban after TAVI (no prior atrial fibrillation) had a higher mortality and thromboembolic events as well as higher bleeding event rates.

The TEG(R) 6S analyzer is a point-of-care system evaluating a patient's individual hemostasis profile by thrombelastography (TEG(R)), a potentially superior tool compared to conventional platelet function testing. The TEG(R) system has been able to predict thrombotic complications in different clinical contexts.

In classic coronary interventional cardiology, the strength of adenosine diphosphate (ADP)-induced and thrombin-induced platelet-fibrin clots were found to be indicators of long-term poststenting ischemic events. As the pathophysiologic mechanism of subclinical leaflet thrombosis has not been examined in detail, the investigators hypothesize that several TEG(R) assays may provide insight in finding predictive TEG(R) markers. Furthermore, as the onset of subclinical leaflet thrombosis is not clear and may possibly increase over time, the design with subsequent TEG(R) analyses at 3 timepoints (0, 3, 6 months) will help to hopefully identify predictors that may become evident at later time points.

It is intriguing to hypothesize that the better predictive marker may be found using the Global Hemostasis Assay. This is relevant as leaflet thrombosis develops despite dual antiplatelet therapy and anticoagulation has been shown to fully resolve subclinical leaflet thrombosis. The Global Hemostasis Assay may deliver prediction beyond platelet function, which may improve antithrombotic therapy post TAVI. Finding a predictive TEG marker (examining Platelet Mapping and Global Hemostasis together) holds the promise for future individualized clinical decision-making by identifying individual risk.

Taken together, we hope that individual TEG based stratification of patients at risk for subclinical leaflet thrombosis or other events may allow individual clinical decision-making.

Eligibility criteria: Inclusion Criteria:

- Patients are eligible for enrollment if they are scheduled for TAVI using a commercially available valve after clinical decision making within the local Heart Team.

Exclusion Criteria:

* Valve-in-valve TAVI and prior valve thrombosis
* Severely impaired renal function (e.g. creatinine clearance \< 30ml/min)
* poor CT imaging if the presence of HALT cannot be assessed.

Primary outcomes:
measure: Global TEG(R)-based prediction of hypoattenuating leaflet thickening (HALT)
timeFrame: 6 months
measure: Platelet TEG(R)-based prediction of hypoattenuating leaflet thickening (HALT)
timeFrame: 6 months
Secondary outcomes:
measure: All-cause mortality within 12 months
timeFrame: 12 months
measure: Cardiovascular mortality within 12 months
timeFrame: 12 months
measure: Thromboembolic events within 12 months
timeFrame: 12 months
measure: Bleeding events within 12 months
timeFrame: 12 months
Other outcomes:
measure: Incidence of hypoattenuating leaflet thickening (HALT)
timeFrame: 6 months
Locations:
city: Freiburg
country: Germany
facility: Department of Cardiology and Angiology I, Heart Center Freiburg University
Study officials:
affiliation: Cardiology and Angiology I, Heart Center Freiburg University, Germany
name: Torben Pottgiesser, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cardiology and Angiology I, Heart Center Freiburg University, Germany
name: Daniel Duerschmied, MD
role: STUDY_DIRECTOR
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