Brief Title
Avr Thrombosis OutcoMe Study
Official Title
Can Thrombosis and Fibrinolysis Markers in Patients Undergoing Aortic Valve Replacement Predict Outcome
Brief Summary
This study aims to utilise novel biomarkers assessing thrombosis and thrombolysis (through a
blood test), to identify patients undergoing either surgical aortic valve replacement (SAVR)
or transcatheter aortic valve implantation (TAVI) who are at risk of thrombosis, and relate
this to clinical thrombotic and thromboembolic adverse events and subclinical valve
thrombosis, and identify the timeframe of greatest risk for valve thrombosis.
Detailed Description
Recent studies have highlighted the risk of peri-operative thrombosis in patients undergoing
aortic valve replacement (AVR) and the subsequent risk of subclinical valve thrombosis in
bioprosthetic AVR. The risk is significantly greater with transcatheter aortic valve
implantation (TAVI) than surgical aortic valve replacement (SAVR), and can lead to stroke and
other neurological events including death, and early valve failure secondary to restricted
leaflet mobility.
Whilst oral anticoagulation (OAC) can reduce thrombosis, OAC has been shown to significantly
and unacceptably increase the risk of bleeding when applied to all-comers undergoing TAVI. It
would therefore be desirable to identify which patients are at increased thrombosis risk so
these can be targeted with antithrombotic medications, whilst avoiding unnecessary bleeding
risk in low risk patients.
In this study, we will aim to identify those patients at greatest risk of thrombosis using
novel biomarkers (assessing thrombosis and thrombolysis), and note whether these tests are
able to predict adverse events.
The tests for thrombosis and thrombolysis will involve a blood draw, which will be taken at
various time points in the study to signal the time point of greatest thrombogenicity, which
may be dependent on anti-platelet and anticoagulant therapy that the patient is prescribed.
Adverse events include MACCE (myocardial infarction, stroke, TIA (transient ischaemic attack)
and death), systemic embolism, clinical and subclinical valve thrombosis, valve restriction
and bleeding.
4D CT, echocardiography and clinical reviews will be performed at regular time points in the
study to identify adverse events. The follow-up for each patent will be 5 years.
Study Type
Observational
Primary Outcome
MACCE
Secondary Outcome
Subclinical valve thrombosis
Condition
Aortic Stenosis
Intervention
Blood test
Study Arms / Comparison Groups
Surgical Aortic Valve Replacement (SAVR)
Description: This cohort includes patients who will be undergoing surgical aortic valve replacement
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Diagnostic Test
Estimated Enrollment
750
Start Date
February 1, 2020
Completion Date
January 2028
Primary Completion Date
January 2028
Eligibility Criteria
Inclusion Criteria:
1. Male and female patients aged 18 years or over.
2. Patients diagnosed with aortic valve disease, undergoing surgical or transcatheter AVR
and free of exclusion criteria below.
3. The patient is willing and able to understand the Patient Information Sheet and
provide informed consent.
4. The patient agrees to comply with the study protocol, including phlebotomy and imaging
as required at pre-specified time points.
Exclusion Criteria:
1. Inability to provide valid informed consent.
2. Male and female patients aged < 18 years of age.
3. The patient has, in the opinion of the investigator, significant neurological,
hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, haemorrhagic,
metabolic or other disease likely to confound the study requirements or analyses.
4. The patient has a history of substance abuse or demonstrates signs or clinical
features of active substance abuse or active psychiatric disease that may result in
non-compliance with visits or inability to obtain venous access.
5. Alcohol consumption above recommended safe levels (i.e. more than 14 units per week
owing to the potential effects of high alcohol levels on platelet reactivity).
6. Any illness deemed significant by the investigator during the four (4) weeks preceding
the screening period of the study such as sepsis.
7. Any major bleeding diathesis or blood dyscrasia (platelets < 70 x 109/l, Hb < 8 g/dl,
INR > 1.4, APTT > x 2 UNL, leucocyte count < 3.5 x 109/l, neutrophil count < 1 x
109/l).
8. Currently enrolled in an investigational device or drug trial.
9. Active or disseminated malignancy at the time of recruitment.
Additionally, for those patients taking part in the additional 4D CT angiography
substudy:
10. Any contraindications to CT angiography: renal failure (Cr>250 μmol/L or eGFR<30
mL/min) due to the additional risk of contrast medium nephrotoxicity; or allergy to
iodine.
11. Women of childbearing age who have not had a hysterectomy and/or who may be
breastfeeding.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 01707247512, [email protected]
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT04234841
Organization ID
RD2019-11
Responsible Party
Sponsor
Study Sponsor
East and North Hertfordshire NHS Trust
Collaborators
Royal Brompton & Harefield NHS Foundation Trust
Study Sponsor
, ,
Verification Date
January 2020