Clinical trial NCT02826200: Rule Out Transcatheter Aortic Valve Thrombosis With Post Implantation Computed Tomography (RETORIC)
Official title: Rule Out Transcatheter Aortic Valve Thrombosis With Post Implantation Computed Tomography
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Prosthetic Cardiac Valve Thrombosis
Cerebrovascular Accident
Prosthetic Valve Malfunction
Keywords: Transcatheter aortic valve implantation
Transcatheter aortic valve replacement
Prosthetic Cardiac Valve Thrombosis
Cerebrovascular Accident
Prosthetic Valve Malfunction
Four-dimensional volume rendered cardiac CT
Transesophageal echocardiography
Transthoracic echocardiography
Brain MRI
Lead sponsor: Semmelweis University Heart and Vascular Center
Sponsor class: OTHER
First posted: 2016-07-07
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The RETORIC study is a prospective cohort study with a primary aim to assess the incidence and independent predictors of reduced leaflet motion and valve thrombosis after TAVI procedure using multimodality imaging strategy comprising cardiac CT, transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE). As a secondary aim we will assess the incidence of stroke and transient ischemic attack (TIA) in patients with reduced leaflet motion and/or thrombosis when compared with those with normal leaflet function. In addition we will randomize patients with reduced leaflet motion and/or valve thrombosis to single antiplatelet therapy plus oral anticoagulation therapy versus standard therapy.

The primary outcome of the nested randomized trial will be the presence of reduced leaflet motion and/or valve thrombosis after 4 months, the secondary outcome is the presence of ischemic changes in brain demonstrated by MRI.

Detailed description: Transcatheter aortic valve implantation (TAVI) is an established treatment for severe aortic stenosis in patients non-eligible for surgical aortic valve replacement. Prosthetic valve thrombosis is defined as a thrombus that is attached to any part of the prosthesis, and is not caused by infection. This may result in valve dysfunction and/or thromboembolisation. Most patients with prosthetic valve thrombosis are asymptomatic, whereas some patients present with stroke or transient ischemic attack (TIA). Obstructive prosthetic valve thrombosis may lead to overt congestive heart failure.

Currently, there is no strict guideline recommendation regarding therapeutic anticoagulation after TAVI. Per institutional protocol dual antiplatelet therapy is used during the first 6 months after THV implantation and single antiplatelet therapy is used after after 6 months.

Diagnosing transcatheter heart valve (THV) thrombosis is of clinical importance even in asymptomatic patients, because it may lead to thromboembolism and can cause THV dysfunction. Therefore, early diagnosis and treatment may prevent future TIA or stroke and THV dysfunction. Current standard clinical practice and guidelines are inconsistent regarding the antithrombotic treatment of patients who underwent TAVI procedure. Accordingly, determining the true incidence and potential causative factors of THV thrombosis is of great importance and would facilitate further investigations and large clinical trials in order to develop optimal antithrombotic treatment of patients following TAVI procedure.

The RETORIC study is a prospective cohort study with a primary aim to assess the incidence and independent predictors of reduced leaflet motion and valve thrombosis after TAVI procedure using multimodality imaging strategy comprising cardiac CT, transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE). As a secondary aim we will assess the incidence of stroke and TIA in those with reduced leaflet motion and thrombosis when compared with those with normal leaflet function. In addition we will randomise patients with reduced leaflet motion to unchanged standard therapy versus single antiplatelet plus oral anticoagulation therapy. The primary outcome of this nested randomized trial will be the presence of novel ischemic lesions in brain demonstrated by MRI.

Findings of the RETORIC study may alter current post-TAVI diagnostic work up and treatment algorithm regarding anticoagulant and antiplatelet therapies.

In total 200 patients who underwent or are undergoing TAVI procedure will be included into the RETORIC study. The institutional standard of care post-TAVI antithrombotic medication consists of six months dual antiplatelet treatment with clopidogrel and aspirin followed by lifelong aspirin therapy.

Currently, the TAVI procedure number at our institution is approximately 80 patients/year. Therefore, to reach our enrolment goal of 200 patients, subjects will be enrolled from two cohorts.

Cohort A: Patients who underwent TAVI procedure in the past will be selected from the Semmelweis TAVI Registry. For this cohort a median TAVI-to-CT time will be calculated.

Cohort B: Patients undergoing TAVI procedure will be enrolled consecutively. In this group the imaging will be performed 3 months after the prosthesis implantation in every patient.

Four-dimensional cardiac CT, TTE and brain MRI data will be obtained in all patients. In case the cardiac CT identifies reduced leaflet motion or THV thrombosis TEE exam will be performed even in asymptomatic patients and patients will enter the randomized control trial. Patients will be randomized into two groups:

Group 1, standard therapy plus oral anticoagulant therapy; Group 2, standard therapy. After 4 months patients will undergo four-dimensional cardiac CT, TTE and brain MRI.

The primary outcome of the randomized trial will be the presence of reduced leaflet motion/valve thrombosis, secondary outcome will be the presence of ischemic lesions on brain MRI images.

Eligibility criteria: Inclusion Criteria:

* TAVI procedure
* Signed ethics committee-approved informed consent form

Exclusion Criteria:

* Age under 18 years
* Patients for whom multidetector-row computed tomography is contraindicated per institutional standard of care (History of severe and/or anaphylactic contrast reaction, severe renal insufficiency, inability to cooperate with scan acquisition and/or breathhold instructions)
* Patients diagnosed with infective endocarditis since TAVI procedure

Primary outcomes:
measure: Reduced leaflet motion and/or valve thrombosis
timeFrame: 4 months
Secondary outcomes:
measure: Presence of ischemic brain lesions
timeFrame: 4 months
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Heart and Vascular Center, Semmelweis University
Study officials:
affiliation: Semmelweis University Heart and Vascular Center
name: Béla Merkely, MD, PhD, DSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Semmelweis University Heart and Vascular Center
name: Pál Maurovich-Horvat, MD, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Guy's and St Thomas' NHS Foundation Trust, Kings College London
name: Ronak Rajani, MD MRCP BM
role: STUDY_CHAIR
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