Use of Dabigatran Etexilate to Prevent Stroke and Thromboembolism

• Sponsor: Vanderbilt University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01976507
• Collaborator: Boehringer Ingelheim (Industry)
• Enrollment: 101
• Location: 1
• Arm: 1
• Actual Duration (Months): 38
• Patients Per Site Per Month: 2.7

Study Details

Study Description

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

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: N/A
• 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: Oct 1, 2013
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

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 Names: Pradaxa

Outcome Measures

Primary Outcome Measures

1. Frequency of Major Bleeding Complications in Patients Administered Dabigatran Following RF Ablation. [Within 4 months following procedure (+/- 4 days)]

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

2. Number of Participants With Minor Bleeding Events [Within 4 months following procedure (+/- 4 days)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Christopher Ellis, Assistant Professor of Medicine, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT01976507
• Other Study ID Numbers: 121204
• First Posted: Nov 5, 2013
• Last Update Posted: Sep 12, 2017
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Atrial Fibrillation; Thromboembolism; Atrial Flutter; Dabigatran

Study Results

Participant Flow

Arm/Group Title	Dabigatran Etexilate Mesylate
Arm/Group Description	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. 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.
Period Title: Overall Study
STARTED	101
Received Initial Dose of Dabigatran	100
COMPLETED	94
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Dabigatran Etexilate Mesylate
Arm/Group Description	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. 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.
Overall Participants	100
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	61 (12)
Sex: Female, Male (Count of Participants)
Female	28 28%
Male	72 72%
Region of Enrollment (participants) [Number]
United States	100 100%

Outcome Measures

1. Primary Outcome

Title	Frequency of Major Bleeding Complications in Patients Administered Dabigatran Following RF Ablation.
Time Frame	Within 4 months following procedure (+/- 4 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dabigatran Etexilate Mesylate
Arm/Group Description	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. 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.
Measure Participants	100
Number [number of events]	1

2. Primary Outcome

Title	Frequency of Major Thrombo-embolic Events in Patients Administered Dabigatran Following RF Ablation.
Time Frame	Within 4 months following procedure (+/- 4 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dabigatran Etexilate Mesylate
Arm/Group Description	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. 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.
Measure Participants	100
Number [number of events]	0

3. Secondary Outcome

Title	Dabigatran Serum Drug Levels in Patients Experiencing a Major Bleeding or Thrombo-embolic Event.
Time Frame	Within 4 months following procedure (+/- 4 days)

Outcome Measure Data

Analysis Population Description

This measure was removed from the protocol. No blood draws were done on any participants.

Arm/Group Title	Dabigatran Etexilate Mesylate
Arm/Group Description	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. 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.
Measure Participants	0

4. Secondary Outcome

Title	Number of Participants With Minor Bleeding Events
Time Frame	Within 4 months following procedure (+/- 4 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dabigatran Etexilate Mesylate
Arm/Group Description	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. 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.
Measure Participants	94
Count of Participants [Participants]	3 3%

Adverse Events

Arm/Group Title	Dabigatran Etexilate Mesylate
Arm/Group Description	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. 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.
All Cause Mortality
	Dabigatran Etexilate Mesylate
	Affected / at Risk (%)	# Events
Total	0/100 (0%)
Serious Adverse Events
	Dabigatran Etexilate Mesylate
	Affected / at Risk (%)	# Events
Total	1/100 (1%)
Blood and lymphatic system disorders
Pericardial Effusion with Tamponade	1/100 (1%)	1
Other (Not Including Serious) Adverse Events
	Dabigatran Etexilate Mesylate
	Affected / at Risk (%)	# Events
Total	14/100 (14%)
Cardiac disorders
Pericardial Pain/Pericarditis	1/100 (1%)	1
Gastrointestinal disorders
Upper Gi Symptoms	5/100 (5%)	5
Tarry Stools	3/100 (3%)	3
Musculoskeletal and connective tissue disorders
Fracture	1/100 (1%)	1
Nervous system disorders
Migraine with Aura	1/100 (1%)	1
Respiratory, thoracic and mediastinal disorders
Pleuritic Pain	1/100 (1%)	1
Pneumonia	1/100 (1%)	1
Surgical and medical procedures
Carotid Stenosis/Carotid Endarterectomy	1/100 (1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.