Post-Operative Atrial Fibrillation
Conditions
Keywords
Left Atrial Appendage, Anticoagulation, CHA2DS2- VASc, HASBLED
Brief summary
Patients without a documented history of Atrial Fibrillation (AF) and will undergo a valve or Coronary Artery Bypass Graft (CABG) procedure with direct visual access to the Left Atrial Appendage (LAA) will be eligible to participate. Patients enrolled will be randomized 2:1 (2 with AtriClip to 1 without AtriClip. Subjects who develop Post-operative Atrial Fibrillation (POAF) and receive the AtriClip will be followed for 365 days post index procedure.
Detailed description
Patients without a documented history of AF but who present with a CHA2DS2- VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke or transient ischemic attack (TIA), vascular disease, age 65 to 74 years, sex category) of =\> 2 and HASBLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) of =\> 2 and will undergo a valve or CABG (structural heart) procedure with direct visual access to the LAA will be eligible to participate based upon the inclusion and exclusion criteria defined in this protocol. Up to 2000 patients will enroll at up to 40 sites and will be randomized 2:1 (2 with AtriClip to 1 without AtriClip. Subjects who not develop Post-operative Atrial Fibrillation (POAF) will be followed for 30 days for safety. Subjects who develop POAF and receive the AtriClip will be followed for 365 days post index procedure.
Interventions
DEVICEAtriClip® Gillinov-Cosgrove™ LAA Exclusion Systems
Anticoagulation Therapy- Standard of Care at the discretion of the Investigator.
Sponsors
AtriCure, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients satisfying the following criteria will be considered the screening population and will be eligible for participation: * Age \> 18 years male or female. * Scheduled for any non-mechanical valve and/or CABG (structural heart) procedure where direct access to the LAA is expected. * No documented preoperative AF. * CHA2DS2-VASc score of =\> 2. * HASBLED score of =\> 2. * Acceptable surgical candidate, including use of general anesthesia. * Willing and able to provide written informed consent.
Exclusion criteria
Patients satisfying the following criteria will not be eligible for participation: * Redo cardiac surgery. * Mechanical heart valve or other anticipated or current requirement for anticoagulation therapy during the post-operative (30 day) period. * Hypercoagulability conditions that may confound the study. * Ejection Fraction \< 30. * Left Atrium \> 6 cm. * Severe Diastolic Dysfunction. * Requires anticoagulation therapy. * Patient had a stroke/cerebrovascular accident (CVA) within previous 30 days prior to signing informed consent. Intra-Operative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Perioperative Complications Associated With AtriClip Placement | Within any 24 hour period during the first 2 days post-index procedure | Defined as: stroke, major bleeding that requires re-operation and/or transfusion of \> 2 U packed red blood cells (PRBC), myocardial infarction (MI), or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite Event Rates for ALL Subjects Regardless of POAF Through 365 Days | 365 Days Post-Procedure | Events to be evaluated include: Thromboembolic & Hemorrhagic Events such as cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral ischemia, hemorrhagic stroke, neurologic bleed, gastrointestinal (GI) bleeds, or other major bleeding event. |
| Number of Subjects With Intraoperative Successful Exclusion of LAA. | Intraoperative period | Successful exclusion of LAA is defined as no (0 mm) flow between LAA and LA and \< 5 mm LAA remnant by intraoperative TEE with Doppler. |
| Composite Event Rates Between Subjects Diagnosed With Post-operative Atrial Fibrillation (POAF) (Through 365 Days) | 365 days post index procedure | Events to be evaluated include: Thromboembolic & Hemorrhagic Events such as cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral ischemia, hemorrhagic stroke, neurologic bleed, gastrointestinal (GI) bleeds, or other major bleeding event. |
| Composite Event Rates Between Subjects Not Diagnosed With POAF (Through 30 Days) | 30 days Post-Procedure | Events to be evaluated include: Thromboembolic & Hemorrhagic Events such as cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral ischemia, hemorrhagic stroke, neurologic bleed, gastrointestinal (GI) bleeds, or other major bleeding event. |
| Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | 365 Days Post-Procedure | Healthcare resource utilization variance between groups as related to hospital length-of-stay (LOS) and hospital readmissions. |
| Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | 365 Days Post-Procedure | Specifically, reoperation for bleeding, neurologic consults for stroke or TIA, and emergency department (ED) visits. |
| Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | 365 Days Post-Procedure | Healthcare resource utilization variance between groups as related to hospital length-of-stay (LOS) and hospital readmissions. |
Countries
United States
Participant flow
Recruitment details
Patients without a documented history of Atrial Fibrillation (AF) but who presented with a CHA2DS2- VASc of =\> 2 and HASBLED of =\> 2 and were to undergo a valve or CABG (structural heart) procedure with direct visual access to the Left Atrial Appendage (LAA) were recruited to participate based upon the inclusion and exclusion criteria defined in the protocol. A total of 562 participants were enrolled across 23 sites. The study visits took place between February 2016 and April 2019.
Pre-assignment details
Prior to randomization, transesophageal echocardiography (TEE) with Doppler was performed to assess for presence of thrombus. If a thrombus was present in the left atrium (LA) or LAA, the subject was not included in the study.
Participants by arm
| Arm | Count |
|---|---|
| AtriClip® LAA Exclusion with AtriClip®: AtriClip® is used per label and is not experimental.
AtriClip® Gillinov-Cosgrove™ LAA Exclusion Systems | 376 |
| No AtriClip® Medical Management: Standard of Care Oral Anticoagulation Therapy at the discretion of the Investigator.
Other Names:
* Warfarin/Coumadin
* New oral anticoagulants (NOACs): dabigatran, rivaroxaban, apixaban
No AtriClip® used. | 186 |
| Total | 562 |
Baseline characteristics
| Characteristic | AtriClip® | No AtriClip® | Total |
|---|---|---|---|
| Age, Continuous | 69.2 years STANDARD_DEVIATION 7.8 | 68.9 years STANDARD_DEVIATION 8.7 | 69.1 years STANDARD_DEVIATION 8.1 |
| BMI (kg/m²) | 31.0 kg/m² STANDARD_DEVIATION 5.6 | 30.0 kg/m² STANDARD_DEVIATION 5.9 | 30.6 kg/m² STANDARD_DEVIATION 5.7 |
| Echocardiogram: Left Atrial Diameter (cm) | 3.9 cm | 3.9 cm STANDARD_DEVIATION 0.6 | 4.0 cm STANDARD_DEVIATION 0.6 |
| Echocardiogram: Left Ventricular Ejection Fraction % | 60.0 % | 60.0 % | 57.8 % STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 5 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 370 Participants | 180 Participants | 550 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaskan Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 5 Participants | 2 Participants | 7 Participants |
| Race/Ethnicity, Customized Race Black or African American | 13 Participants | 7 Participants | 20 Participants |
| Race/Ethnicity, Customized Race More Than One Race | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Race White | 354 Participants | 171 Participants | 525 Participants |
| Region of Enrollment United States | 376 participants | 186 participants | 562 participants |
| Risk Assessment: CHA2DS2VASc Score | 3.4 units on a scale STANDARD_DEVIATION 1.2 | 3.4 units on a scale STANDARD_DEVIATION 1.1 | 3.4 units on a scale STANDARD_DEVIATION 1.2 |
| Risk Assessment: HAS-BLED Score | 2.8 units on a scale STANDARD_DEVIATION 0.7 | 2.9 units on a scale STANDARD_DEVIATION 0.6 | 2.8 units on a scale STANDARD_DEVIATION 0.7 |
| Sex: Female, Male Female | 113 Participants | 50 Participants | 163 Participants |
| Sex: Female, Male Male | 263 Participants | 136 Participants | 399 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 20 / 376 | 4 / 186 |
| other Total, other adverse events | 1 / 376 | 0 / 0 |
| serious Total, serious adverse events | 1 / 376 | 0 / 0 |
Outcome results
Primary
Number of Perioperative Complications Associated With AtriClip Placement
Defined as: stroke, major bleeding that requires re-operation and/or transfusion of \> 2 U packed red blood cells (PRBC), myocardial infarction (MI), or death.
Time frame: Within any 24 hour period during the first 2 days post-index procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AtriClip® | Number of Perioperative Complications Associated With AtriClip Placement | 0 perioperative complications reported |
Secondary
Composite Event Rates Between Subjects Diagnosed With Post-operative Atrial Fibrillation (POAF) (Through 365 Days)
Events to be evaluated include: Thromboembolic & Hemorrhagic Events such as cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral ischemia, hemorrhagic stroke, neurologic bleed, gastrointestinal (GI) bleeds, or other major bleeding event.
Time frame: 365 days post index procedure
Population: Analysis includes only subjects diagnosed with POAF through 365 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AtriClip® | Composite Event Rates Between Subjects Diagnosed With Post-operative Atrial Fibrillation (POAF) (Through 365 Days) | 19.6 percent of participants |
| AtriClip Without OAC | Composite Event Rates Between Subjects Diagnosed With Post-operative Atrial Fibrillation (POAF) (Through 365 Days) | 8.2 percent of participants |
| Standard of Care With OAC | Composite Event Rates Between Subjects Diagnosed With Post-operative Atrial Fibrillation (POAF) (Through 365 Days) | 16.0 percent of participants |
| Standard of Care Without OAC | Composite Event Rates Between Subjects Diagnosed With Post-operative Atrial Fibrillation (POAF) (Through 365 Days) | 6.5 percent of participants |
| Combined Standard of Care | Composite Event Rates Between Subjects Diagnosed With Post-operative Atrial Fibrillation (POAF) (Through 365 Days) | 9.9 percent of participants |
p-value: 0.2593Fisher Exact
Secondary
Composite Event Rates Between Subjects Not Diagnosed With POAF (Through 30 Days)
Events to be evaluated include: Thromboembolic & Hemorrhagic Events such as cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral ischemia, hemorrhagic stroke, neurologic bleed, gastrointestinal (GI) bleeds, or other major bleeding event.
Time frame: 30 days Post-Procedure
Population: Analysis includes only subjects not diagnosed with POAF through 365 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AtriClip® | Composite Event Rates Between Subjects Not Diagnosed With POAF (Through 30 Days) | 5.0 percent of participants |
| AtriClip Without OAC | Composite Event Rates Between Subjects Not Diagnosed With POAF (Through 30 Days) | 5.1 percent of participants |
| Standard of Care With OAC | Composite Event Rates Between Subjects Not Diagnosed With POAF (Through 30 Days) | 0.0 percent of participants |
| Standard of Care Without OAC | Composite Event Rates Between Subjects Not Diagnosed With POAF (Through 30 Days) | 8.0 percent of participants |
| Combined Standard of Care | Composite Event Rates Between Subjects Not Diagnosed With POAF (Through 30 Days) | 7.8 percent of participants |
p-value: 1Fisher Exact
Secondary
Composite Event Rates for ALL Subjects Regardless of POAF Through 365 Days
Events to be evaluated include: Thromboembolic & Hemorrhagic Events such as cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral ischemia, hemorrhagic stroke, neurologic bleed, gastrointestinal (GI) bleeds, or other major bleeding event.
Time frame: 365 Days Post-Procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AtriClip® | Composite Event Rates for ALL Subjects Regardless of POAF Through 365 Days | 15.8 percent of participants |
| AtriClip Without OAC | Composite Event Rates for ALL Subjects Regardless of POAF Through 365 Days | 6.7 percent of participants |
| Standard of Care With OAC | Composite Event Rates for ALL Subjects Regardless of POAF Through 365 Days | 8.5 percent of participants |
| Standard of Care Without OAC | Composite Event Rates for ALL Subjects Regardless of POAF Through 365 Days | 14.8 percent of participants |
| Combined Standard of Care | Composite Event Rates for ALL Subjects Regardless of POAF Through 365 Days | 7.5 percent of participants |
| Combined Standard of Care | Composite Event Rates for ALL Subjects Regardless of POAF Through 365 Days | 8.6 percent of participants |
p-value: 0.1238Fisher Exact
Secondary
Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates)
Specifically, reoperation for bleeding, neurologic consults for stroke or TIA, and emergency department (ED) visits.
Time frame: 365 Days Post-Procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AtriClip® | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | Reoperation | 3.9 percentage of participants |
| AtriClip® | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | ED Visit | 9.2 percentage of participants |
| AtriClip® | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | Neurologic Consult | 2.6 percentage of participants |
| AtriClip® | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | Hospital Readmission | 11.8 percentage of participants |
| AtriClip Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | ED Visit | 3.3 percentage of participants |
| AtriClip Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | Neurologic Consult | 2.7 percentage of participants |
| AtriClip Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | Hospital Readmission | 3.7 percentage of participants |
| AtriClip Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | Reoperation | 2.7 percentage of participants |
| Standard of Care With OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | Neurologic Consult | 3.7 percentage of participants |
| Standard of Care With OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | ED Visit | 7.4 percentage of participants |
| Standard of Care With OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | Hospital Readmission | 7.4 percentage of participants |
| Standard of Care With OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | Reoperation | 3.7 percentage of participants |
| Standard of Care Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | Hospital Readmission | 2.5 percentage of participants |
| Standard of Care Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | ED Visit | 4.4 percentage of participants |
| Standard of Care Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | Reoperation | 1.3 percentage of participants |
| Standard of Care Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Event Rates) | Neurologic Consult | 4.4 percentage of participants |
Comparison: Reoperationp-value: 0.5442Fisher Exact
Comparison: ED Visitp-value: 0.2598Fisher Exact
Comparison: Neurologic Consultp-value: 0.5442Fisher Exact
Comparison: Hospital Readmission (per subject)p-value: 0.2921Fisher Exact
Secondary
Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values)
Healthcare resource utilization variance between groups as related to hospital length-of-stay (LOS) and hospital readmissions.
Time frame: 365 Days Post-Procedure
Population: In LOS (Total), 1 Subject removed due to incorrect date entry
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AtriClip® | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | LOS (Total) | 9.1 days | Standard Deviation 7 |
| AtriClip® | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | Readmission LOS (per subject) | 6.1 days | Standard Deviation 4.1 |
| AtriClip® | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | LOS (Post-Procedure) | 7.7 days | Standard Deviation 5.3 |
| AtriClip Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | LOS (Total) | 8.1 days | Standard Deviation 5.2 |
| AtriClip Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | Readmission LOS (per subject) | 4.7 days | Standard Deviation 3.4 |
| AtriClip Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | LOS (Post-Procedure) | 6.4 days | Standard Deviation 3.8 |
| Standard of Care With OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | LOS (Post-Procedure) | 7.7 days | Standard Deviation 3.1 |
| Standard of Care With OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | LOS (Total) | 8.4 days | Standard Deviation 3.5 |
| Standard of Care With OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | Readmission LOS (per subject) | 21.0 days | Standard Deviation 18.4 |
| Standard of Care Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | LOS (Total) | 7.3 days | Standard Deviation 4.4 |
| Standard of Care Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | Readmission LOS (per subject) | 7.0 days | Standard Deviation 8.3 |
| Standard of Care Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Mean Values) | LOS (Post-Procedure) | 5.9 days | Standard Deviation 2.7 |
Comparison: LOS (Total)p-value: 0.6603t-test, 2 sided
Comparison: LOS (Post-Procedure)p-value: 0.0783t-test, 2 sided
Comparison: Readmission LOS (per subject)p-value: 0.4282t-test, 2 sided
Secondary
Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values)
Healthcare resource utilization variance between groups as related to hospital length-of-stay (LOS) and hospital readmissions.
Time frame: 365 Days Post-Procedure
Population: In LOS (Total), 1 Subject removed due to incorrect date entry
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| AtriClip® | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | LOS (Total) | 7.0 days |
| AtriClip® | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | Readmission LOS (per subject) | 5.0 days |
| AtriClip® | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | LOS (Post-Procedure) | 6.0 days |
| AtriClip Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | LOS (Total) | 7.0 days |
| AtriClip Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | Readmission LOS (per subject) | 5.0 days |
| AtriClip Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | LOS (Post-Procedure) | 5.0 days |
| Standard of Care With OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | LOS (Post-Procedure) | 7.0 days |
| Standard of Care With OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | LOS (Total) | 9.0 days |
| Standard of Care With OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | Readmission LOS (per subject) | 21.0 days |
| Standard of Care Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | LOS (Total) | 6.0 days |
| Standard of Care Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | Readmission LOS (per subject) | 4.0 days |
| Standard of Care Without OAC | Healthcare Resource Utilization Variance Between Groups as Related to the Composite Events Above (Median Values) | LOS (Post-Procedure) | 5.0 days |
p-value: 0.6603t-test, 2 sided
Comparison: LOS (Post-Procedure)p-value: 0.0783t-test, 2 sided
Comparison: Readmission LOS (per subject)p-value: 0.4282t-test, 2 sided
Secondary
Number of Subjects With Intraoperative Successful Exclusion of LAA.
Successful exclusion of LAA is defined as no (0 mm) flow between LAA and LA and \< 5 mm LAA remnant by intraoperative TEE with Doppler.
Time frame: Intraoperative period
Population: Of the 376 surgical cases where placement of an AtriClip was attempted:~* 3 AtriClip devices were not implanted~* 2 patients could not have the intra-operative TEE imaging assessments verified post-operatively and were removed from the LAA exclusion analyses for stump and flow.~* 1 patient that had a reported stump did not have an assessment for flow recorded.~Therefore, 370 patients had complete data available to assess intra-operative LAA exclusion success.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AtriClip® | Number of Subjects With Intraoperative Successful Exclusion of LAA. | Total Patients, No Flow and No Stump | 82.2 percentage of participants |
| AtriClip® | Number of Subjects With Intraoperative Successful Exclusion of LAA. | Total Patients, No Flow with Stump <= 5mm | 95.4 percentage of participants |
| AtriClip® | Number of Subjects With Intraoperative Successful Exclusion of LAA. | Total Patients, No Flow with Stump <= 10mm | 98.9 percentage of participants |