1. To investigate the safety of omission of clopidogrel compared to a strategy using aspirin + clopidogrel during 1 year follow-up in patients without an indication for OAC after TAVI (Cohort A);2. To investigate the safety of omission of…
ID
Source
Brief title
Condition
- Cardiac valve disorders
- Cardiac therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary safety outcome is defined as all and non-procedure related bleeding
(primarily classified according to BARC(Mehran et al., 2011) and also TIMI(Mega
et al., 2009; Sabatine et al., 2009) and GUSTO(The GUSTO Investigators, 1993)).
Secondary outcome
Secondary net-clinical benefit outcome is a composite of cardiovascular
mortality, non-procedural bleeding, stroke, and myocardial infarction.
Secondary efficacy outcome is a composite of cardiovascular mortality, ischemic
stroke, and myocardial infarction.
Furthermore, we will register the composites of the primary and secondary
outcomes, all-cause mortality, rehospitalisation and time to rehospitalisation,
vascular complication (VC), number of blood transfusions, cardiac tamponade,
transient ischemic attack (TIA), acute kidney injury, myocardial infarction and
damage, prosthetic valve thrombosis, transvalvular aortic gradients, effective
aortic valve area, paravalvular regurgitation, NYHA functional classification,
combined early safety according to the VARC-2 Consensus(Kappetein et al.,
2012), cost-effectiveness, frailty, and quality of life.
Background summary
At present, a variety of antithrombotic regimens are prescribed in the early
postoperative period after transcatheter aortic valve implantation (TAVI). Dual
antiplatelet therapy (DAPT) in the initial period after TAVI is the recommended
strategy; however, mono antiplatelet therapy is suggested not to be inferior.
In patients with atrial fibrillation (AF) or another indication for oral
anticoagulation (OAC), no recommendations on best treatment regimen currently
exist although triple therapy is best avoided. We hypothesise that the omission
of Clopidogrel in the first 3 months after TAVI is safe and not less effective
than the addition of Clopidogrel to Aspirin or OAC.
Study objective
1. To investigate the safety of omission of clopidogrel compared to a strategy
using aspirin + clopidogrel during 1 year follow-up in patients without an
indication for OAC after TAVI (Cohort A);
2. To investigate the safety of omission of clopidogrel compared to a strategy
using OAC + clopidogrel during 1 year follow-up in patients with an indication
for OAC after TAVI (Cohort B).
3. To investigate the net-clinical benefit of omission of clopidogrel during 1
year follow-up in patients with and without an indication for OAC after TAVI
(Cohort A + B);
4. To investigate the efficacy of omission of clopidogrel during 1 year
follow-up in patients with and without an indication for OAC after TAVI (Cohort
A + B);
5. To investigate the effects of genetic variations of CYP2C19 and PTGS2 on
clinical outcomes.
6. To investigate the effect of omission of clopidogrel on costeffectiveness,
functional parameters, and quality of life.
Study design
Multicentre open-label randomized controlled trial with all-comers design
(Cohort A + B). The safety endpoint will be analysed for superiority whereas
the net-clinical benefit and efficacy endpoint will be analysed for
non-inferiority.
Intervention
1. Random 1:1 allocation to aspirin alone (at least until 1 year)
(intervention) versus clopidogrel (3 months) + aspirin (at least until 1 year)
(control), 1 day before TAVI in patients without an indication for OAC at
baseline (Cohort A);
2. Random 1:1 allocation to OAC alone (intervention) versus OAC + clopidogrel
(3 months) (control), 1 day before TAVI in patients with an indication for OAC
at baseline (Cohort B).
Study burden and risks
Antithrombotic regimen in high risk TAVI population is a double-edged sword.
While DAPT reduces thrombo-embolic risk, it increases haemorrhagic risk.
Moreover, antiplatelet therapy in addition to OAC in patients with AF carries a
more than 3-fold higher bleeding risk(Hansen et al., 2010). A pilot study did
not support a strategy of short-term adjunctive use of Clopidogrel added to
Aspirin after TAVI(Ussia et al., 2011), so no additional risk or burden is
expected from the study*s intervention.
The number of site visits is not increased compared to regular follow-up after
TAVI, and no additional invasive tests are used than routinely required.
Patients will be asked to complete health survey*s (i.e. EuroQol 5D (EQ-5D) and
12-Item Short Form Health Survey (SF-12)) at follow-up. No physical and/or
psychological discomfort associated with participation is expected.
Patients that agree to participate with the MRI substudy of the AMC Medical
Center and St Antonius hospital, will undergo two MRI scans of the brain. The
total duration of the MRI scan is 15 minutes and will be performed < 72 hours
before the TAVI procedure and 3 months following TAVI.
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Listed location countries
Age
Inclusion criteria
Cohort A
1. Patient has provided written informed consent.;Cohort B
1. Need for long-term oral anticoagulation;
2. Patient has provided written informed consent.
Exclusion criteria
Cohort A
1. Need for long-term oral anticoagulation.
2. Drug-eluting stent implantation within 3 months prior to TAVI procedure.
3. Bare-metal stent implantation within 1 month prior to TAVI procedure.
4. Allergy or intolerance or contraindication to aspirin or clopidogrel.;Cohort B
1. Drug-eluting stent implantation within 3 months prior to TAVI procedure.
2. Bare-metal stent implantation within 1 month prior to TAVI procedure.
3. Allergy or intolerance or contraindication to OAC or clopidogrel.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-003125-28-NL |
| CCMO | NL45668.100.13 |