Clinical trial NCT04234841: Avr Thrombosis OutcoMe Study
Official title: Can Thrombosis and Fibrinolysis Markers in Patients Undergoing Aortic Valve Replacement Predict Outcome
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Aortic Stenosis
Keywords: TAVI
SAVR
Lead sponsor: East and North Hertfordshire NHS Trust
Sponsor class: OTHER_GOV
Collaborators: name: Royal Brompton & Harefield NHS Foundation Trust
First posted: 2020-01-21
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients undergoing surgical bioprosthetic aortic valve replacement and transcatheter aortic valve implantation

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.

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.

Primary outcomes:
measure: MACCE
timeFrame: 5 years (total duration of study)
measure: Bleeding
timeFrame: 5 years (total duration of study)
measure: Systemic embolism
timeFrame: 5 years (total duration of study)
Secondary outcomes:
measure: Subclinical valve thrombosis
timeFrame: 5 years (total duration of study)
measure: New/worsening AF
timeFrame: 5 years (total duration of study)
Other outcomes:
Locations:
city: Stevenage
country: United Kingdom
facility: East and North Hertfordshire NHS Trust
state: Hertforshire
Study officials:
References: