Clinical trial NCT01976507: Use of Dabigatran Etexilate to Prevent Stroke and Thromboembolism
Official title: Use of Dabigatran Etexilate to Prevent Stroke and Thromboembolism in Patients Undergoing Left Atrial Catheter Ablation Procedures for Paroxysmal or Persistent (Non-permanent) Atrial Fibrillation and Left Atrial Flutter
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Atrial Flutter
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2013-11-05
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate major adverse bleeding risks, and thromboembolic event rates post radiofrequency (RF) ablation. The primary goal is to establish safety of dabigatran use for peri-procedural anti-coagulation after left atrial catheter radiofrequency ablation, or cryoablation procedures.

Detailed description: Study design

Approximately 100 patients who plan to have pulmonary vein isolation by antral radiofrequency or cryoablation for paroxysmal or persistent atrial fibrillation, or left atrial flutter following prior left atrial ablation procedures, with CHADS2 score of 0-6 or CHADS2-VASc score 0-9 will be eligible for this trial and enrolled. A transesophageal echocardiogram (TEE) will be performed pre-procedure based on the presenting cardiac rhythm the day of planned catheter ablation, stroke risk by CHADS2 or CHADS2-VASc score, and preceding use of therapeutic anti-coagulation (as per current 2012 HRS/ACC/ESC guidelines on atrial fibrillation management). Immediately following the ablation procedure (4-6 hours after sheath pull and vascular hemostasis), dabigatran etexilate 150mg bid, or 75mg twice daily based on creatinine clearance in the Use in Specified Populations (USPI), will be administered for a minimum of 3 months post RF ablation. This represents the standard blanking period for post atrial fibrillation or left atrial flutter catheter ablation anticoagulation therapy. After the 3 months blanking period, patients may safely be taken off dabigatran in the low risk group for stroke or thromboembolism, according to the investigators discretion (CHADS 2 score 0-1, or CHADS2-VASc score 0-1). If on dabigatran etexilate pre-procedure, the drug will be held at least 24 hours before the intervention depending on renal function of the patient (as per recommendations in the USPI). If possible, discontinue dabigatran 1 to 2 days (CrCl \>50 mL/min) or 3 to 5 days (CrCl \<50 mL/min) before an invasive or surgical procedure, due to increased risk of bleeding.

Dabigatran etexilate will be resumed 4-6 hours after sheath pull and vascular hemostasis post ablation as above. Intra-procedure intravenous heparin drip will be started once left atrial access is obtained with an ACT goal target 300-350 seconds by weight based nomogram. Standardized ablation endpoints (4 vein entrance and exit block with post ablation adenosine challenge and/or isoproterenol, or termination of left atrial flutter and completion of linear ablation confirmed by differential pacing) will be documented, along with radiofrequency or cryoablation

delivery time, fluoroscopy and total case time. Inpatient adverse events will be documented, and outpatient follow up will occur at 1 and 3 months post ablation per standard protocol, with documentation of all composite endpoints (see below). In addition, a 30 day post study phone call follow up will be performed (30 days +/- 4 days following the 3 month visit). Please see Table 1 for the schedule of events.

Our hypothesis is that exposure to dabigatran in the setting of AF left atrial catheter ablation will be associated with alow or acceptable risk of major adverse bleeding risks, and low thromboembolic event rates post RF ablation, in accordance with our previous data, and in contrary to the findings of Lakireddy, et al, in their retrospective study published 2012 in JACC. This could lead to widespread utilization of dabigatran etexilate for centers performing a high number of atrial fibrillation and left atrial flutter ablation procedures.

Eligibility criteria: Inclusion Criteria:

* Male or female sex, age 18-85 years.
* Negative pregnancy test for women of childbearing potential
* Planned pulmonary vein isolation by antral radiofrequency or cryoablation for paroxysmal or persistent atrial fibrillation, non-valvular atrial fibrillation (NVAF), or left atrial flutter following prior left atrial ablation procedures
* CHADS2 score of 0-6 or CHADS2-VASc score 0-9
* Vascular hemostasis within 4-6 hours of sheath pull
* Able to give informed consent

Exclusion Criteria:

* Unable to give informed consent
* Currently participating in another clinical treatment trial
* History of hereditary hemophilias
* Presence of active bleeding
* End stage renal disease, CrCl\<15 mL/min
* Prior treatment failure of dabigatran (stroke or systemic thromboembolism while on therapeutic dabigatran)
* Known allergic reaction to dabigatran etexilate
* Intolerance to dabigatran, if medication naïve, or other contra-indications as per the USPI.
* Pregnancy
* History of non-compliance
* Inability to follow-up

Primary outcomes:
measure: Frequency of Major Bleeding Complications in Patients Administered Dabigatran Following RF Ablation.
timeFrame: Within 4 months following procedure (+/- 4 days)
measure: Frequency of Major Thrombo-embolic Events in Patients Administered Dabigatran Following RF Ablation.
timeFrame: Within 4 months following procedure (+/- 4 days)
Secondary outcomes:
measure: Dabigatran Serum Drug Levels in Patients Experiencing a Major Bleeding or Thrombo-embolic Event.
timeFrame: Within 4 months following procedure (+/- 4 days)
measure: Number of Participants With Minor Bleeding Events
timeFrame: Within 4 months following procedure (+/- 4 days)
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Christopher R Ellis, MD
role: PRINCIPAL_INVESTIGATOR
References: