Paroxysmal Atrial Fibrillation
Conditions
Keywords
Anticoagulation, Oral, Paroxysmal atrial fibrillation, Patients post successful cardiac ablation, Symptomatic high-burden paroxysmal AF, 3 months post procedure, Remain free from AF recurrence
Brief summary
The objective of this study is to determine the safety of discontinuing oral anticoagulation therapy in high risk patients who have had a successful cardiac ablation and remain AF recurrence free for 3 months post ablation.
Detailed description
Patients undergoing successful cardiac ablation for atrial fibrillation who remain AF recurrence-free 3 months after successful ablation and continue to meet the inclusion/exclusion criteria will be screened for enrollment in the trial. After fulfilling all of the inclusion/exclusion criteria, patients who consent to participate in the study and remain AF recurrence-free will be randomized to one of two study arms: (1) OAT Withdrawal (Test) Group or (2) OAT (Control) Group and participate in the Evaluation Period (12 months).
Interventions
OTHEROff OAT Group (Test)
Discontinuation of OAT Therapy
OTHEROn OAT Group (Control)
Continuation of OAT Therapy
Sponsors
Biosense Webster, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Successful cardiac ablation for AF 2. Documented freedom from AF recurrence (symptomatic or asymptomatic arrhythmic recurrences lasting longer than 30 seconds) 3 months after successful cardiac ablation (AF recurrence during 3-month blanking period is excluded). 3. Patient must have been on a commercially approved anticoagulation therapy for at least two (2) months prior to randomization in the OAT Study. 4. CHADS2 score ≥ 2 or CHA2DS2-VASc score (≥3) 5. Left ventricular ejection fraction \> 25% 6. LA size \< 65 7. High risk for thromboembolic events (i.e., CHADS2 score ≥ 2 or CHA2DS2-VASc score ≥ 3) and require OAT before undergoing cardiac ablation 8. Able and willing to comply with all pre- and follow-up testing and requirements 9. Signed informed consent form 10. Age 18 years or older
Exclusion criteria
1. OAT required for reasons not related to AF (i.e., prosthetic valve, PV stenosis, previous pulmonary embolism, presence of spontaneous echo contrast \[SEC\] at standard echo performed at 3-months follow-up). 2. Any cardiac surgery within the past 60 days (2 months) or valvular cardiac surgical procedure at any time (i.e., ventriculotomy, atriotomy, and valve repair or replacement and presence of a prosthetic valve) 3. Previous myocardial infarction (MI) or a percutaneous coronary intervention PCI within the past 3 months 4. Awaiting cardiac transplantation or other cardiac surgery within the next 365 days (12 months) 5. Documented left atrial thrombus 6. Significant pulmonary disease, (e.g., restrictive pulmonary disease, constrictive or COPD) or any other disease or malfunction of the lungs or respiratory system that produces chronic symptoms 7. Significant medical problem that in the opinion of the investigator would preclude enrollment in this study 8. Women who are pregnant (as evidenced by pregnancy test if pre-menopausal) 9. Acute illness or active systemic infection or sepsis 10. Unstable angina 11. Contraindication to anticoagulation (i.e., heparin, warfarin or another commercially available anticoagulation medication) 12. History of blood clotting or bleeding abnormalities 13. Life expectancy less than 360 days (12 months) 14. Uncontrolled Heart Failure or NYHA Class III or IV heart failure 15. Enrollment in a clinical study evaluating another device or drug, within the past 6 months 16. Unable or unwilling to comply with protocol requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Occurrence of Any Major Thromboembolic Event | 12 months | Composite endpoint represented by the occurrence of any major thromboembolic event (stroke \[i.e., ischemic, hemorrhagic or cryptogenic\] that is an acute onset of a focal neurologic deficit of presumed vascular origin lasting for ≥24 hours or resulting in death) or major hemorrhagic complication (major bleeding) during the 12-month Evaluation Period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Hospitalized With Any Thromboembolic or Major Hemorrhagic Event | 12 months | Hospitalization due to any thromboembolic or major hemorrhagic event during the 12-month Evaluation Period. |
| Percentage of Expired Participants | 12 months | All cause mortality during the 12-month Evaluation Period. |
| Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Physical Component Summary (PCS) | Baseline, 3 months, 12 months | The 36-Item Short Form Health Survey (SF-36) is a validated health-related quality of life (HRQOL) tool used to measure the physical and mental health status of the study population. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 score on the assumption that each question carries equal weight. Scores can be summed together to contribute to two summary scores, a physical component score and a mental component score. The lower the score, the more disability. |
| Percentage of Participants With Minor Bleeds | 12 months | Any clinical bleed that does not meet criteria for a major hemorrhagic event during the 12-month Evaluation Period. |
| Percentage of Participants With Atrial Fibrillation Recurrence | 12 months | Recurrence of atrial fibrillation during the 12-month Evaluation Period. Subjects with recurrence of atrial fibrillation were immediately exited from the study. |
| Percentage of Participants With Repeat Ablation | 12 months | Repeat ablations performed due to recurrence of atrial fibrillation during the 12-month Evaluation Period. Subjects that required a repeat ablation were immediately exited from the study. |
| Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Mental Component Summary (MCS) | Baseline, 3 months, 12 months | The 36-Item Short Form Health Survey (SF-36) is a validated health-related quality of life (HRQOL) tool used to measure the physical and mental health status of the study population. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 score on the assumption that each question carries equal weight. Scores can be summed together to contribute to two summary scores, a physical component score and a mental component score. The lower the score, the more disability. |
Participant flow
Recruitment details
The first subject was enrolled April 17, 2013. The last subject was enrolled January 25, 2019.
Pre-assignment details
This was a prospective, multicenter, randomized, controlled, two arm, 1:1 design. Enrolled subjects N=80 (subjects signed informed consent). 63 subjects underwent study procedures, 17 subjects were excluded prior to randomization. According to protocol, enrolled subjects = subjects who sign the study's informed consent form.
Participants by arm
| Arm | Count |
|---|---|
| Off OAT Group (Test) Discontinuation of OAT Therapy | 32 |
| On OAT Group (Control) Continuation of OAT Therapy | 31 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discontinued Subjects | 6 | 4 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 4 |
Baseline characteristics
| Characteristic | On OAT Group (Control) | Total | Off OAT Group (Test) |
|---|---|---|---|
| Age, Continuous | 66.0 Years STANDARD_DEVIATION 11.09 | 66.9 Years STANDARD_DEVIATION 8.79 | 67.7 Years STANDARD_DEVIATION 5.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 52 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 7 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) White | 28 Participants | 52 Participants | 24 Participants |
| Sex: Female, Male Female | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Male | 21 Participants | 42 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 31 |
| other Total, other adverse events | 0 / 32 | 4 / 31 |
| serious Total, serious adverse events | 6 / 32 | 2 / 31 |
Outcome results
Primary
Number of Participants With Occurrence of Any Major Thromboembolic Event
Composite endpoint represented by the occurrence of any major thromboembolic event (stroke \[i.e., ischemic, hemorrhagic or cryptogenic\] that is an acute onset of a focal neurologic deficit of presumed vascular origin lasting for ≥24 hours or resulting in death) or major hemorrhagic complication (major bleeding) during the 12-month Evaluation Period.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Off OAT Group (Test) | Number of Participants With Occurrence of Any Major Thromboembolic Event | 0 Number of Participants |
| On OAT Group (Control) | Number of Participants With Occurrence of Any Major Thromboembolic Event | 0 Number of Participants |
Secondary
Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Mental Component Summary (MCS)
The 36-Item Short Form Health Survey (SF-36) is a validated health-related quality of life (HRQOL) tool used to measure the physical and mental health status of the study population. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 score on the assumption that each question carries equal weight. Scores can be summed together to contribute to two summary scores, a physical component score and a mental component score. The lower the score, the more disability.
Time frame: Baseline, 3 months, 12 months
Population: The number of participants analyzed at each time point reflects the number of surveys collected at that time point for each group. Participants may have refused to complete the survey, or were exited from the study prior to the visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Off OAT Group (Test) | Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Mental Component Summary (MCS) | Mean Score at Baseline | 51.5 Points on SF-36 scale | Standard Deviation 8.33 |
| Off OAT Group (Test) | Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Mental Component Summary (MCS) | Mean Score at 3 Months | 52.8 Points on SF-36 scale | Standard Deviation 9.94 |
| Off OAT Group (Test) | Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Mental Component Summary (MCS) | Mean Score at 12 Months | 53.2 Points on SF-36 scale | Standard Deviation 8.7 |
| On OAT Group (Control) | Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Mental Component Summary (MCS) | Mean Score at Baseline | 54.8 Points on SF-36 scale | Standard Deviation 8.53 |
| On OAT Group (Control) | Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Mental Component Summary (MCS) | Mean Score at 3 Months | 53.7 Points on SF-36 scale | Standard Deviation 10.47 |
| On OAT Group (Control) | Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Mental Component Summary (MCS) | Mean Score at 12 Months | 53.5 Points on SF-36 scale | Standard Deviation 9.79 |
Secondary
Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Physical Component Summary (PCS)
The 36-Item Short Form Health Survey (SF-36) is a validated health-related quality of life (HRQOL) tool used to measure the physical and mental health status of the study population. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 score on the assumption that each question carries equal weight. Scores can be summed together to contribute to two summary scores, a physical component score and a mental component score. The lower the score, the more disability.
Time frame: Baseline, 3 months, 12 months
Population: The number of participants analyzed at each time point reflects the number of surveys collected at that time point for each group. Participants may have refused to complete the survey, or were exited from the study prior to the visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Off OAT Group (Test) | Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Physical Component Summary (PCS) | Mean Score at Baseline | 49.8 Points on SF-36 scale | Standard Deviation 8.56 |
| Off OAT Group (Test) | Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Physical Component Summary (PCS) | Mean Score at 3 Months | 52.3 Points on SF-36 scale | Standard Deviation 6.85 |
| Off OAT Group (Test) | Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Physical Component Summary (PCS) | Mean Score at 12 Months | 49.3 Points on SF-36 scale | Standard Deviation 8.6 |
| On OAT Group (Control) | Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Physical Component Summary (PCS) | Mean Score at Baseline | 50.0 Points on SF-36 scale | Standard Deviation 8.24 |
| On OAT Group (Control) | Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Physical Component Summary (PCS) | Mean Score at 3 Months | 50.3 Points on SF-36 scale | Standard Deviation 8.66 |
| On OAT Group (Control) | Mean SF-36 Quality of Life Scores of Participants at Baseline, 3 Months, and 12 Months: Physical Component Summary (PCS) | Mean Score at 12 Months | 50.0 Points on SF-36 scale | Standard Deviation 7.06 |
Secondary
Percentage of Expired Participants
All cause mortality during the 12-month Evaluation Period.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Off OAT Group (Test) | Percentage of Expired Participants | 0 Percentage of Participants |
| On OAT Group (Control) | Percentage of Expired Participants | 0 Percentage of Participants |
Secondary
Percentage of Participants Hospitalized With Any Thromboembolic or Major Hemorrhagic Event
Hospitalization due to any thromboembolic or major hemorrhagic event during the 12-month Evaluation Period.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Off OAT Group (Test) | Percentage of Participants Hospitalized With Any Thromboembolic or Major Hemorrhagic Event | 3.1 Percentage of Participants |
| On OAT Group (Control) | Percentage of Participants Hospitalized With Any Thromboembolic or Major Hemorrhagic Event | 0 Percentage of Participants |
Secondary
Percentage of Participants With Atrial Fibrillation Recurrence
Recurrence of atrial fibrillation during the 12-month Evaluation Period. Subjects with recurrence of atrial fibrillation were immediately exited from the study.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Off OAT Group (Test) | Percentage of Participants With Atrial Fibrillation Recurrence | 18.8 Percentage of Participants |
| On OAT Group (Control) | Percentage of Participants With Atrial Fibrillation Recurrence | 12.9 Percentage of Participants |
Secondary
Percentage of Participants With Minor Bleeds
Any clinical bleed that does not meet criteria for a major hemorrhagic event during the 12-month Evaluation Period.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Off OAT Group (Test) | Percentage of Participants With Minor Bleeds | 0 Percentage of Participants |
| On OAT Group (Control) | Percentage of Participants With Minor Bleeds | 3.2 Percentage of Participants |
Secondary
Percentage of Participants With Repeat Ablation
Repeat ablations performed due to recurrence of atrial fibrillation during the 12-month Evaluation Period. Subjects that required a repeat ablation were immediately exited from the study.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Off OAT Group (Test) | Percentage of Participants With Repeat Ablation | 0 Percentage of Participants |
| On OAT Group (Control) | Percentage of Participants With Repeat Ablation | 0 Percentage of Participants |