See section 2.2. of the protocol.The primary objective of this trial is to assess the safety of an uninterrupted dabigatran etexilate periprocedural anticoagulant regimen compared to an uninterrupted warfarin regimen in NVAF patients undergoing AF…
ID
Source
Brief title
Condition
- Cardiac arrhythmias
- Vascular therapeutic procedures
- Vascular injuries
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint for this trial is a safety endpoint:
* The incidence of Major Bleeding Events according to the ISTH definition
during the ablation procedure and up to 2 months post-ablation.
Secondary outcome
The secondary endpoints for this trial are the incidence of the following
efficacy and safety
endpoints:
*- Stroke/SE/TIA events during the ablation procedure and up to 2 months
post-ablation.
*- Minor bleeding events during the ablation procedure and up to 2 months
postablation.
*- A composite of major bleeding events and thromboembolic events (Stroke, SE
and TIA) during the ablation procedure and up to 2 months post-ablation.
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. Chronic anticoagulant treatment is mandatory in the great majority
of patients with AF.
Catheter ablation is currently recommended in the guidelines as an
interventional alternative for the treatment of patients with AF. During AF
ablation, there is a measurable risk of thromboembolic complication (stroke,
transient ischemic attack (TIA), peripheral embolism) due to the pro-thrombotic
effects of AF itself, the instrumentation of the left atrium (transseptal
access), due to restoration of sinus rhythm/ cardioversion, and the disruption
of the atrial endocardium during application of radiofrequency (RF) energy.
Minimizing these complications by optimal periprocedural anticoagulation with
an appropriate balance between thrombosis and bleeding is critical to the
efficacy and safety of the procedure.
The current standard of care is to anticoagulate patients with a vitamin K
antagonist (VKA) (target international normalized ratio [INR] range 2.0-3.0)
for at least 1 month pre-ablation and for 2-3 months post-ablation regardless
of CHA2DS2-VASc score. In the past it was usual practice to stop VKA before the
ablation to ensure a safe venous access during the procedure. Patients were
bridged with low molecular weight heparin (LMWH) or unfractionated
heparin.(UFH) during the time off VKA pre-procedure and also for a few days
post-ablation until the VKA therapy returned to the target therapeutic range
(INR 2.0-3.0). There is evidence for the superiority of uninterrupted VKA
therapy, with a target INR between 2.0 and 3.0, as a periprocedural
anticoagulant over other interrupted anticoagulation strategies. The current
guidelines state that the
performance of catheter ablation of AF in patients who are therapeutically
anticoagulated with VKA should be considered. In recent years, increasingly
more AF patients are maintained on non-vitamin K oral anticoagulants (NOACs),
posing a management challenge for periprocedural anticoagulation when patients
are scheduled for AF ablation.
Study objective
See section 2.2. of the protocol.
The primary objective of this trial is to assess the safety of an uninterrupted
dabigatran etexilate periprocedural anticoagulant regimen compared to an
uninterrupted warfarin regimen in NVAF patients undergoing AF ablation in a
PROBE (Prospective, randomized, open label, blinded end point) active
controlled study.
Study design
See section 3.1 of the protocol.
This study is a prospective, randomised, open label, blinded endpoint (PROBE),
multicentre, active controlled trial and the primary clinical endpoint
is being adjudicated by an IAC in a blinded fashion.
Patients will be randomly assigned to 150 mg dabigatran etexilate b.i.d. or
warfarin in a 1:1 ratio and remain on this treatment for the duration of the
trial.
The screening period will consist of one visit (Visit 1). The patients will be
randomised at Visit 2. Screening and randomisation can be conducted on the same
day.
Pre-ablation period
There will be a pre-ablation period of 4 to 8 weeks.
Ablation procedure
The ablation procedure will be performed after at least 4 weeks of
anticoagulation.
Post-ablation period
Systemic anticoagulation with dabigatran etexilate 150 mg b.i.d. or with
adjusted warfarin (target INR 2.0-3.0) will be continued for 60 days
post-ablation. Patients will be assessed at the time of randomisation, on the
day of the AF ablation procedure and just before discharge (next day or 48
hours after the ablation procedure at the latest) and also on Day 30 and Day
60, which is the end of treatment (EOT) with trial medication. All patients
will have a follow-up visit one week after the EOT visit.
Intervention
Treatment with dabigatran etexilate instead of VKA.
Study burden and risks
The burden for the study is mainly undergoing a TEE, which in most cases is a
standard procedure when a patient needs to undergo an ablation.
The to be expected risks are low, as described in the patient information
sheet. This consist of risks with adverse events like bleeding events. And the
risks during blood draws, ECG, and unforeseen risks.
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 eligible for treatment with dabigatran etexilate 150 mg b.i.d. according to local label.
- Treatment naïve patients or patients on oral anticoagulant treatment with a VKA, dabigatran etexilate, rivaroxaban, apixaban or edoxaban.
- Patients with paroxysmal or persistent NVAF with a planned catheter ablation for AF unless it is performed an investigational ablation technique.
- AF must have been documented at least once within 24 months prior to screening (Visit 1).
- The patient must be able to give informed consent in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and local legislation and/or regulations.
Exclusion criteria
- Patients with permanent AF.
- Patients with AF felt to be secondary to an obvious reversible cause.
- Patients with LA size >= 60 mm
- Patients with contraindications to systemic anticoagulation with heparin, warfarin or dabigatran etexilate
- Patients with a known allergy to warfarin tablets and it excipients or to dabigatran etexilate or its excipients
- Mechanical or biological heart valve prosthesis
- Severe renal impairment
- Stroke within 1 month prior to screening visit
- Major surgery per investigator judgement within the previous month prior to screening.
- Patient has received an organ transplant or is on a waiting list for an organ transplant
- History of intracranial haemorrhage, intraocular, spinal, retroperitoneal or non-traumatic intra-articular bleeding
- Gastrointestinal haemorrhage within one month prior to screening, unless, in the opinion of the investigator, the cause has been permanently eliminated (e.g. by surgery).
- Major bleeding episode (ISTH definition) one month prior to the screening visit.
- Haemorrhagic disorder or bleeding diathesis
- Anaemia or thrombocytopenia including heparin-induced thrombocytopenia at screening
- Recent malignancy or radiation therapy (<=6 months prior to screening) unless, in the opinion of the Investigator, the estimated life expectancy is greater than 36 months
- Active liver disease
- Need for continued treatment with systemic ketoconazole, itraconazole, posaconazole cyclosporine, tacrolimus, dronedarone, rifampicin, phenytoin, carbamazepine, St. John*s Wort or any cytotoxic/myelosuppressive therapy.
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 | EUCTR2014-003890-40-NL |
| ClinicalTrials.gov | NCT02348723 |
| CCMO | NL51969.060.15 |