See section 2.2 of the protocol.The main objective of this study is to compare a DAT regimen of 110mg dabigatran etexilate b.i.d. plus clopidogrel or ticagrelor (110mg DE-DAT) and 150mg dabigatran etexilate b.i.d. plus clopidogrel or ticagrelor (…
ID
Source
Brief title
Condition
- Cardiac arrhythmias
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
See section 5.1.1 of the protocol.
The primary endpoint for this trial is a safety endpoint; time to first ISTH
Major or Clinically Relevant Non-Major Bleeding Event
Secondary outcome
See section 5.1.2 of the protocol.
The secondary endpoints of efficacy are (all time to first event):
1. A combined endpoint of thrombotic events or death (DTE: all death + MI +
stroke/SE) and unplanned revascularisation by PCI/CABG
2. A combined endpoint of thrombotic events or death (DTE: all death + MI +
stroke/SE)
3. Individual outcome events:
**All death (Cardiovascular, Non-cardiovascular, Undetermined)
**MI
**Stroke
**SE
**Stent thrombosis
4. Composite endpoint of death + MI + stroke
5. Repeated revascularisation by PCI/CABG
Background summary
See section 1.1 of the protocol.
The current estimate of the prevalence of atrial fibrillation (AF) in the
developed world is approximately 1.5*2% of the general population. The
arrhythmia is associated with a fivefold increase in the risk of stroke and a
three-fold increase in the incidence of congestive heart failure and higher
mortality. Twenty to thirty percent of non valvular AF (NVAF) patients have
concomitant coronary artery disease.
In patients undergoing PCI, the addition of clopidogrel to aspirin (ASA)
reduces death, myocardial infarction (MI) and stroke. When patients with AF
that are receiving anticoagulant treatment have to undergo a PCI with stenting,
there is an indication for concomitant treatment with ASA and clopidogrel
(triple antithrombotic therapy (TAT)) to prevent stent thrombosis.
Rigorous antithrombotic treatment invariably raises the risk of bleeding,
adding to a poorer prognosis with an estimated five-fold mortality increase
following MI. An acceptable bleeding risk while maintaining a lower ischaemic
event rate is considered a must in the post-PCI setting.
In patients with ACS or undergoing PCI, the presence of AF raises a therapeutic
challenge because treatment with both anticoagulant and antiplatelet therapies
is preferred to prevent stroke and further coronary events.
Studies suggest there might be a potential benefit with the implementation of a
dual antithrombotic therapy (DAT) regimen (anticoagulant plus clopidogrel) in
comparison with a TAT regimen (anticoagulant plus clopidogrel plus ASA) in NVAF
that have undergone PCI.
Study objective
See section 2.2 of the protocol.
The main objective of this study is to compare a DAT regimen of 110mg
dabigatran etexilate b.i.d. plus clopidogrel or ticagrelor (110mg DE-DAT) and
150mg dabigatran etexilate b.i.d. plus clopidogrel or ticagrelor (150mg DE-DAT)
with a TAT combination of warfarin plus clopidogrel or ticagrelor plus ASA *
100mg once daily (q.d.) (warfarin-TAT) in patients with NVAF that undergo a PCI
with stenting (elective or due to an ACS).
Study design
See section 3.1 of the protocol.
This is a prospective, randomised, open label, blinded endpoint (PROBE), active
comparator trial and the clinical endpoints are being adjudicated by an IAC in
a blinded fashion. Patients will be consented and screened after undergoing a
successful PCI.
Patients aged < 80 years will be randomly assigned to 110mg dabigatran
etexilate b.i.d., 150mg dabigatran etexilate b.i.d. or warfarin in a 1:1:1
ratio for the duration of the trial.
Patients aged *80 years will be randomly assigned depending on their
geographical location:
**Patients aged *80 years in the USA will be assigned to 110mg dabigatran
etexilate b.i.d., 150mg dabigatran etexilate b.i.d. or warfarin in a 1:1:1 ratio
**All other patients aged *80 years outside of the USA will be assigned to
110mg dabigatran etexilate or warfarin in a 1:1 ratio.
In addition to their randomised treatment:
**All patients will receive either clopidogrel (75mg q.d.) or ticagrelor (90mg
b.i.d), according to the local label, for at least 12 months after
randomisation.
**Patients randomised to receive warfarin will receive ASA (* 100mg q.d.) for
either one month in patients with a bare metal stent BMS and for three months
in patients with a DES.
Intervention
Treatment with dabigatran etexilate instead of VKA.
Study burden and risks
Considering a study duration of 31 months, the following study activities will
be done:
- Physical exam * 2x
- Blood pressure * 9x
- ECG * 5x
- Blood draw * 10x
- INR monitoring (warfarin group) * every 2-4 weeks, 4ml per blood sample
- Urine pregnancy test * 10x
Comeniusstraat 6
Alkmaar 1817 MS
NL
Comeniusstraat 6
Alkmaar 1817 MS
NL
Listed location countries
Age
Inclusion criteria
- Male or female patients aged ><=18 years;- Patients with Non Valvular Atrial Fibrillation;- Patient presenting with:;An ACS (STEMI, NonSTEMI [NSTEMI] or unstable angina [UA]) that was successfully treated by PCI and stenting (either Bare Metal Stent or Drug Eluting Stent);Or;Stable Coronary Artery Disease with at least one lesion eligible for PCI that was successfully treated by elective PCI and stenting (either BMS or DES) ;- The patient must be able to give informed consent in accordance with International Conference on Harmonisation Good Clinical Practice guidelines and local legislation and/or regulations.
Exclusion criteria
- Patients with a mechanical or biological heart valve prosthesis;- Cardiogenic shock during current hospitalisation;- Stroke within 1 month prior to screening visit;- Patients who have had major surgery within the month prior to screening;- Gastrointestinal haemorrhage within one month prior to screening, unless, in the opinion of the Investigator, the cause has been permanently eliminated;- Major bleeding episode including life-threatening bleeding episode in one month prior to screening visit;- Anaemia (haemoglobin <=10g/dL) or thrombocytopenia including heparin-induced thrombocytopenia (platelet count <=100 x 109/L) at screening;- Severe renal impairment (estimated CrCl calculated by Cockcroft-Gault equation) <=30mL/min at screening;- Active liver disease
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 | EUCTR2013-003201-26-NL |
| CCMO | NL49746.060.14 |