Use of Dabigatran Etexilate to Prevent Stroke and Thromboembolism

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation; Atrial Flutter	Drug: dabigatran etexilate mesylate	Phase 4

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	101 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Actual Study Start Date :	October 2013
Actual Primary Completion Date :	December 2016
Actual Study Completion Date :	December 2016

Arms and Interventions

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Arm	Intervention/treatment
Experimental: dabigatran etexilate mesylate; 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.	Drug: dabigatran etexilate mesylate; 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.; Other Name: Pradaxa

Outcome Measures

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Primary Outcome Measures :

1. Frequency of Major Bleeding Complications in Patients Administered Dabigatran Following RF Ablation. [ Time Frame: Within 4 months following procedure (+/- 4 days) ]
2. Frequency of Major Thrombo-embolic Events in Patients Administered Dabigatran Following RF Ablation. [ Time Frame: Within 4 months following procedure (+/- 4 days) ]

Secondary Outcome Measures :

1. Dabigatran Serum Drug Levels in Patients Experiencing a Major Bleeding or Thrombo-embolic Event. [ Time Frame: Within 4 months following procedure (+/- 4 days) ]
2. Number of Participants With Minor Bleeding Events [ Time Frame: Within 4 months following procedure (+/- 4 days) ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 85 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Vanderbilt University Medical Center

Boehringer Ingelheim

Investigators

Principal Investigator:	Christopher R Ellis, MD	Vanderbilt University

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Christopher Ellis, Assistant Professor of Medicine, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier:	NCT01976507 History of Changes
Other Study ID Numbers:	121204
First Posted:	November 5, 2013
Results First Posted:	September 12, 2017
Last Update Posted:	September 12, 2017
Last Verified:	August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Additional relevant MeSH terms:

Atrial Fibrillation; Thromboembolism; Atrial Flutter; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Embolism and Thrombosis	Vascular Diseases; Dabigatran; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants