Use of Dabigatran Etexilate to Prevent Stroke and Thromboembolism

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by Vanderbilt University
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Christopher Ellis, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01976507
First received: October 29, 2013
Last updated: June 4, 2015
Last verified: June 2015
  Purpose

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 Intervention Phase
Atrial Fibrillation
Atrial Flutter
Drug: dabigatran etexilate mesylate
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
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

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Frequency of major bleeding complications and thrombo-embolic events in patients administered dabigatran following RF ablation. [ Time Frame: Within 4 months following procedure (+/- 4 days) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Dabigatran serum drug levels in patients experiencing a major bleeding or thrombo-embolic event. [ Time Frame: Within 4 months following procedure (+/- 4 days) ] [ Designated as safety issue: Yes ]
  • Frequency of minor bleeding events [ Time Frame: Within 4 months following procedure (+/- 4 days) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: October 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01976507

Contacts
Contact: Sherry Bowman, RN 615-875-5500

Locations
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Christopher Ellis, MD       christopher.ellis@vanderbilt.edu   
Principal Investigator: Christopher R Ellis, MD         
Sub-Investigator: Sean P Whalen, MD         
Sponsors and Collaborators
Vanderbilt University
Boehringer Ingelheim
Investigators
Principal Investigator: Christopher R Ellis, MD Vanderbilt University
  More Information

No publications provided

Responsible Party: Christopher Ellis, Assistant Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01976507     History of Changes
Other Study ID Numbers: 121204
Study First Received: October 29, 2013
Last Updated: June 4, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Atrial Fibrillation
Atrial Flutter
Thromboembolism
Arrhythmias, Cardiac
Cardiovascular Diseases
Embolism and Thrombosis
Heart Diseases
Pathologic Processes
Thrombosis
Vascular Diseases
Dabigatran
Anticoagulants
Antithrombins
Enzyme Inhibitors
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Serine Proteinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on July 05, 2015