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Trial registered on ANZCTR


Registration number
ACTRN12619000080123
Ethics application status
Approved
Date submitted
1/01/2019
Date registered
21/01/2019
Date last updated
21/01/2019
Date data sharing statement initially provided
21/01/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Prothrombotic changes during aortic valve management
Scientific title
Characterising the prothrombotic changes associated with transcatheter aortic valve implantation: the key to promoting the rational use of anti-thrombotic prophylaxis and minimizing devastating thromboembolic and bleeding complications
Secondary ID [1] 295242 0
None
Universal Trial Number (UTN)
U1111-1215-9691
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
transcatheter aortic valve implantation 308428 0
percutaneous coronary intervention 308429 0
aortic valve replacement 308430 0
thrombosis 308431 0
bleeding 308432 0
Condition category
Condition code
Cardiovascular 307416 307416 0 0
Other cardiovascular diseases
Anaesthesiology 307417 307417 0 0
Anaesthetics
Surgery 307418 307418 0 0
Other surgery

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
In addition to routine clinical care, eligible consenting participants will be agreeing to the following:

1. access to their medical records for:
a) the completion of standardised data collection forms to identify pre-existing risk factors for thrombosis, bleeding or vascular disease, and to assign surgical-risk scores; and,
b) for the completion of standardised procedural record considering all aspects of the procedure with implications for coagulation;

2. Collection of blood samples at procedure-specific pre-specified timepoints at 5 occasions prior to, during and following the procedure. These samples will be processed for:
a) point of care coagulation tests (comprising: ROTEMSigma, TEG6s, activated clotting time and Multiple analysers);
b) standard laboratory testing (comprising: full blood count, coagulation tests [PT/INR, aPTT, direct fibrinogen], anti-xa assay)
c) processing to, storage and transport of platelet poor plasma for specialised coagulation tests
Intervention code [1] 301593 0
Diagnosis / Prognosis
Intervention code [2] 313309 0
Early Detection / Screening
Comparator / control treatment
The primary group will be patients undergoing transcatheter aortic valve implantation (TAVI). Comparator groups will be patients undergoing percutaneous coronary intervention (PCI) and surgical aortic valve replacement (SAVR).
Control group
Active

Outcomes
Primary outcome [1] 307617 0
Point of care coagulation measurement of clot strength.
Timepoint [1] 307617 0
All study cohorts (PCI, TAVI and AVR) will have POCCT testing conducted at procedure-specific timepoints ranging from pre-procedure to 6 hours post-procedure.

The primary timepoint for each procedure will be that showing the largest value for prothrombotic change from baseline in the primary outcomes. The definition of T1 - T5 is different for each procedure. It is anticipated that this change will be most evident at T3 for each procedure which is defined for the TAVI group as post-TAVI deployment; PCI, as post-stent deployment; and, AVR, 20 min post-aortic cannulation.
Primary outcome [2] 318627 0
Point of care coagulation measurement of clotting time.
Timepoint [2] 318627 0
All study cohorts (PCI, TAVI and AVR) will have POCCT testing conducted at procedure-specific timepoints ranging from pre-procedure to 6 hours post-procedure.

The primary timepoint for each procedure will be that showing the largest value for prothrombotic change from baseline in the primary outcomes. The definition of T1 - T5 is different for each procedure. It is anticipated that this change will be most evident at T3 for each procedure which is defined for the TAVI group as post-TAVI deployment; PCI, as post-stent deployment; and, AVR, 20 min post-aortic cannulation.
Primary outcome [3] 318629 0
Point of care coagulation measure of clot formation.
Timepoint [3] 318629 0
All study cohorts (PCI, TAVI and AVR) will have POCCT testing conducted at procedure-specific timepoints ranging from pre-procedure to 6 hours post-procedure.

The primary timepoint for each procedure will be that showing the largest value for prothrombotic change from baseline in the primary outcomes. The definition of T1 - T5 is different for each procedure. It is anticipated that this change will be most evident at T3 for each procedure which is defined for the TAVI group as post-TAVI deployment; PCI, as post-stent deployment; and, AVR, 20 min post-aortic cannulation.
Secondary outcome [1] 352459 0
Incidence of clinically significant bleeding or clotting complications as reported by the treating clinicians or identified in the medical records during the peri- and post-operative phases will be considered as secondary outcomes.
Timepoint [1] 352459 0
72 hours post-procedure.
Secondary outcome [2] 365538 0
Whole blood platelet aggregometry area under the curve.
Timepoint [2] 365538 0
Baseline.
Secondary outcome [3] 365543 0
von Willebrand factor or vWF levels (using immunoblotting for high- and low-molecular weight vWF)
Timepoint [3] 365543 0
Change over procedure-specific timepoints as previously identified. Procedure-specific timepoints defined as:
TF-TAVI: T1, post-anaesthetic/pre-cannulation; T2, 10 min post heparin/pre-BAV/TAVI; T3, post-TAVI deployment; T4, 10-20 min post-protamine; T5, 6 hr post-procedure.
PCI: T1, post-cannulation, pre-wire insertion; T2, 10 min post-heparin; T3, post-stent deployment; T4, 10-20 min post-protamine; T5, 6 hr post-procedure.
AVR: T1, post-anaesthetic induction / pre-incision; T2, 10 min post-heparin; T3, 20 min post-aortic cannulation; T4, 10 - 20 min post-protamine; T5, 6 hr post-procedure.
Secondary outcome [4] 365544 0
Hemolysis defined by measuring the plasma free haemoglobin level (using UV/visible spectrophotometer).
Timepoint [4] 365544 0
Change over procedure-specific timepoints as previously identified. Procedure-specific timepoints defined as:
TF-TAVI: T1, post-anaesthetic/pre-cannulation; T2, 10 min post heparin/pre-BAV/TAVI; T3, post-TAVI deployment; T4, 10-20 min post-protamine; T5, 6 hr post-procedure.
PCI: T1, post-cannulation, pre-wire insertion; T2, 10 min post-heparin; T3, post-stent deployment; T4, 10-20 min post-protamine; T5, 6 hr post-procedure.
AVR: T1, post-anaesthetic induction / pre-incision; T2, 10 min post-heparin; T3, 20 min post-aortic cannulation; T4, 10 - 20 min post-protamine; T5, 6 hr post-procedure.
Secondary outcome [5] 365545 0
Platelet count (haematology analyser)
Timepoint [5] 365545 0
Change over procedure-specific timepoints as previously identified. Procedure-specific timepoints defined as:
TF-TAVI: T1, post-anaesthetic/pre-cannulation; T2, 10 min post heparin/pre-BAV/TAVI; T3, post-TAVI deployment; T4, 10-20 min post-protamine; T5, 6 hr post-procedure.
PCI: T1, post-cannulation, pre-wire insertion; T2, 10 min post-heparin; T3, post-stent deployment; T4, 10-20 min post-protamine; T5, 6 hr post-procedure.
AVR: T1, post-anaesthetic induction / pre-incision; T2, 10 min post-heparin; T3, 20 min post-aortic cannulation; T4, 10 - 20 min post-protamine; T5, 6 hr post-procedure.

Eligibility
Key inclusion criteria
1) Informed consent for participation;
2) Either: i) severe aortic stenosis (aortic valve area <0.8cm2, mean aortic valve gradient >40mmHg or peak jet velocity >4m/s); AND planned management with either a TF-TAVI or isolated AVR; OR, ii) Non-ST elevation myocardial infarction (new ischaemic ECG criteria, troponin > upper limit of normal, clinical symptoms); AND planned management with elective PCI; 3) Stable haemoglobin > 100g/l; 4) Non-emergency procedure; 5) Preserved ejection fraction (>50%).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Lack of capacity to consent for him or herself; 2) Medications known to: i) interact with coagulation assays; or ii) have a known or suspected prothrombotic or coagulopathic action that cannot be corrected for by the analysers used for point of care coagulation testing; 3) Known or suspected bleeding or clotting disorders; 4) Severe liver, renal, respiratory or psychiatric disease (including substance abuse); 5) Enrolled in another study with a non-standard treatment intervention.

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Univariate cross-sectional time-based random effects models will be developed for each viscoelastic measure using the laboratory clotting indices in turn as the dependent variable. Both: i) paired comparisons between timepoints; and, ii) univariate time-series regression will also analysed for each variable.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 12056 0
St Andrew's War Memorial Hospital - Brisbane
Recruitment postcode(s) [1] 24213 0
4000 - Brisbane

Funding & Sponsors
Funding source category [1] 299833 0
Charities/Societies/Foundations
Name [1] 299833 0
Wesley Medical Research Institute
Address [1] 299833 0
Level 8, East Wing, The Wesley Hospital
451 Coronation Drive, Auchenflower QLD 4066
Country [1] 299833 0
Australia
Funding source category [2] 301527 0
Government body
Name [2] 301527 0
Health Investment, Innovation and Research Office, Office of the Director-Genera, Department of Health, Queensland Government
Address [2] 301527 0
Level 13
33 Charlotte Street
Brisbane Qld 4000
Country [2] 301527 0
Australia
Primary sponsor type
Hospital
Name
St. Andrew's War Memorial Hospital
Address
457 Wickham Terrace
Spring Hill
QLD, 4001
Country
Australia
Secondary sponsor category [1] 301227 0
Hospital
Name [1] 301227 0
The Princess Alexandra Hospital
Address [1] 301227 0
199 Ipswich Road
Woolloongabba
QLD, 4102
Country [1] 301227 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300710 0
Uniting Care Health Human Research Ethics Committee
Ethics committee address [1] 300710 0
The Wesley Hospital
451 Coronation Drive, Auchenflower
QLD 4066
Ethics committee country [1] 300710 0
Australia
Date submitted for ethics approval [1] 300710 0
21/07/2016
Approval date [1] 300710 0
24/01/2017
Ethics approval number [1] 300710 0
2016.33.213
Ethics committee name [2] 302420 0
Metro South Health
Ethics committee address [2] 302420 0
Metro South
Human Research Ethics Committee
Centres for Health Research
Level 7, TRI
37 Kent Street
Woolloongabba
Ethics committee country [2] 302420 0
Australia
Date submitted for ethics approval [2] 302420 0
19/11/2018
Approval date [2] 302420 0
16/01/2019
Ethics approval number [2] 302420 0
LNR/2018/QMS/46866

Summary
Brief summary
Aortic stenosis (AS) is the most common heart valve disease in the Western World. Transcatheter aortic valve implantation (TAVI) has substantially expanded the therapeutic options available to patients suffering from severe AS. However, despite the rapidly expanding clinical use of TAVI, patients remain at high risk for both thrombotic/clotting (e.g., stroke and valve thrombosis) and bleeding complications. Optimal preventative therapy is essential to minimise thrombosis without incurring excessive bleeding risk. Current recommendations for clot prevention in TAVI are extrapolated from heart vessel stunting (also known as percutaneous coronary intervention or PCI) data despite significant patient and procedural differences that likely result in different risk profiles. Until this is addressed, clinicians are left to advise and treat their patients without essential information.

This observational study will recruit 40 patients undergoing TAVI, PCI and AVR to compare the clotting / bleeding changes that occur during the procedure. Blood will be sampled from each patient at 5 time points depending on the procedure. These blood samples will be assessed for the bleeding / clotting potential of the blood at that time using the latest blood clotting tests including ROTEMSigma, TEG6s, MultiPlate and various other specialised laboratory tests.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84562 0
Dr Jonathon P Fanning
Address 84562 0
Level 3, Clinical Sciences Building
The Prince Charles Hospital
Rode Road
Chermside, QLD, 4032
Country 84562 0
Australia
Phone 84562 0
+61 07 3139 4000
Fax 84562 0
Email 84562 0
jonathon.fanning@ccrg.org.au
Contact person for public queries
Name 84563 0
Dr Jonathon P Fanning
Address 84563 0
Level 3, Clinical Sciences Building
The Prince Charles Hospital
Rode Road
Chermside, QLD, 4032
Country 84563 0
Australia
Phone 84563 0
+61 07 3139 4000
Fax 84563 0
Email 84563 0
jonathon.fanning@ccrg.org.au
Contact person for scientific queries
Name 84564 0
Dr Jonathon P Fanning
Address 84564 0
Level 3, Clinical Sciences Building
The Prince Charles Hospital
Rode Road
Chermside, QLD, 4032
Country 84564 0
Australia
Phone 84564 0
+61 07 3139 4000
Fax 84564 0
Email 84564 0
jonathon.fanning@ccrg.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD sharing was not included in the ethical application nor consent forms for this study.
What supporting documents are/will be available?
Study protocol
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 915 0
Informed consent form
Citation [1] 915 0
Link [1] 915 0
Email [1] 915 0
Other [1] 915 0
Type [2] 916 0
Study protocol
Citation [2] 916 0
Link [2] 916 0
Email [2] 916 0
Other [2] 916 0
Type [3] 917 0
Ethical approval
Citation [3] 917 0
Link [3] 917 0
Email [3] 917 0
Other [3] 917 0
Type [4] 1111 0
Ethical approval
Citation [4] 1111 0
Link [4] 1111 0
Email [4] 1111 0
Other [4] 1111 0
Summary results
No Results