Aortic Valve Stenosis, Atrial Fibrillation
Conditions
Brief summary
To evaluate the safety and effectiveness of the left atrial appendage occlusion with WATCHMAN Device in prevention of stroke and bleeding in patients with atrial fibrillation (AF) undergoing transcatheter aortic valve replacement (TAVR).
Detailed description
WATCH-TAVR is a prospective, multicenter, randomized controlled trial. Only centers with approval for commercial WATCHMAN implantation will be included in this trial. Subjects will be enrolled at up to 32 centers in the United States. There will be up to 350 subjects enrolled, with 175 patients randomized to TAVR + medical therapy and 175 patients randomized to simultaneous TAVR+WATCHMAN to accumulate the necessary 191 primary events. Enrollment is expected to occur over the course of 18 months. Patients will be followed for a total of 2 years. Patients with non-valvular AF undergoing standard of care commercial TAVR will be enrolled in the trial. For patients who receive the WATCHMAN device, plan of care will follow WATCHMAN labeling.Patients randomized to receive the WATCHMAN device will receive anticoagulation with warfarin and aspirin for 6 weeks after the procedure. After 6 weeks, the plan of care will follow WATCHMAN labeling. Patients randomized to the TAVR + medical therapy arm will be treated in accordance with standard of care with either warfarin, other anticoagulant/antiplatelet therapy, or no anticoagulation at the discretion of the treating physician. All patients will continue to receive routine post-TAVR follow-up and care.Patients will be monitored for primary and secondary endpoints as outlined. Baseline information and laboratory data will be collected as described in the protocol. At trial conclusion, total number of subjects enrolled was 349. There were 172 subjects enrolled in the TAVR + Medical Therapy arm and 177 subjects enrolled in the TAVR + WATCHMAN arm.
Interventions
DEVICEWATCHMAN
WATCHMAN Device is composed of a self-expanding nitinol structure with a porous membrane on the proximal face. The implant device is delivered to the Left Atrial Appendage by femoral venous access and transseptal puncture to enter the left atrium.
DEVICETAVR
Transcatheter Aortic Valve Replacement
Sponsors
Boston Scientific Corporation
The Cleveland Clinic
samir kapadia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Patients will be randomized in a 1:1 allocation ratio to the following treatment arms TAVR + Medical Therapy (n=175) or simultaneous TAVR + WATCHMAN (n=175)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men and women ≥ 18 years of age. 2. The patient meets criteria for and is scheduled to undergo TAVR procedure 3. The patient has documented paroxysmal, persistent, or permanent atrial fibrillation. 4. The patient meets the WATCHMAN labeling guidelines and is eligible to undergo the WATCHMAN implantation procedure. 5. The patient is eligible for short term warfarin therapy. 6. The patient or legal representative is able to understand and willing to provide written informed consent to participate in the trial. 7. The patient is able and willing to return for required follow-up visits and examinations.
Exclusion criteria
1. The patient had a stroke or TIA within the last 6 months prior to enrollment. 2. Contraindication for short term anticoagulation. 3 .Moderate or severe Mitral Stenosis with mean gradient across Mitral Valve \>10 mm Hg or Mitral Valve Area \< 1.2cm2. 4\. The patient has symptomatic carotid disease (i.e.,carotid stenosis ≥ 50% associated with ipsilateral transient or visual TIA evidenced by amaurosis fugax, ipsilateral hemispheric TIAs or ipsilateral stroke within 6 months). 5\. Prior occlusion of LAA. 6\. The patient has an implanted mechanical mitral valve. 7\. The patient requires long-term warfarin therapy due to: 1. Secondary to conditions such as prior arterial embolism or other indications such as pulmonary embolism or deep vein thrombosis within the previous 6 months 2. The patient is in a hypercoaguable state; exclude the patient if per medical record documentation, the patient meets any of the following criteria: * Thrombosis occurring ≤ 40 years of age * Idiopathic or recurrent VTE (venous thrombo-embolism) * Thrombosis at an unusual site (cerebral veins, hepatic veins, renal veins, IVC, mesenteric veins) * Family history of VTE or of inherited prothrombotic disorder, recurrence/extension of thrombosis while adequately anticoagulated. 8\. The patient is actively enrolled in another trial of a cardiovascular device or an investigational drug (post-market study participation and registries are acceptable). 9\. The patient is pregnant or pregnancy is planned during the course of the investigation if patient is of child bearing potential. 10\. Any clinically significant medical condition or presence of any laboratory abnormality prior to randomization that is considered by the investigator to be clinically important and could interfere with the conduct of the study or not meeting procedure guidelines for TAVR or WATCHMAN. 11\. The patient has a life expectancy of less than two years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of All-cause Mortality, Stroke and Bleeding | Through 2 year post-randomization | First occurrence of all-cause mortality, stroke (ischemic or hemorrhagic), or bleeding (life-threatening and major) events through 2 years post-randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality | Through 2 year post-randomization | All deaths through 2 year |
| Stroke | Through 2 year post-randomization | First occurrence of any ischemic or hemorrhagic stroke through 2 year |
| Bleeding | Through 2 year post-randomization | First occurrence of any life-threatening or major bleeding through 2 year |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular Mortality | Through 2 year post-randomization | Cardiovascular related mortality through 2 year |
| Procedural Costs | Mean cost during hospitalization up to 40 days. | Procedural costs related to the initial TAVR and WATCHMAN procedures |
| Thrombus or Embolism | Through 2 year post-randomization | Incidence of arterial or venous embolism |
| Re-hospitalization | Through 2 year post-randomization | Incidence of re-hospitalizations related to the WATCHMAN procedure or WATCHMAN device |
| Quality of Life Score: KCCQ-12 | Through 2 year post-randomization | Change from baseline in quality of life (QoL) as measured using the KCCQ-12 score. Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a validated tool used to assess heart failure and how it affects the participant's life. Four domain scores and one summary score are generated from the KCCQ-12: Physical Limitation Score, Symptom Frequency Score, Quality of Life Score, Social Limitation Score and a Summary Score. Scale ranges for each question 1 to 6 (Extremely limited 1, Quite a bit limited 2, Moderately limited 3, Slightly limited 4, Not at all limited 5, Limited for other reasons or did not do the activity 6. The Summary score represents an integration of the patient's physical limitation, symptom frequency, quality of life and social limitation. The total score is calculated as the average of the above scale descriptions. Scores are scaled 0-100, where 0 denotes the lowest reportable health status. Scores of 100 indicate the highest reportable health better outcome status. |
Countries
United States
Participant flow
Recruitment details
General study population consisted of patients having non-valvular Atrial Fibrillation undergoing standard of care TAVR. Recruitment started December 2017 with the final subject enrolled November 2020. Only medical centers with approval for commercial WATCHMAN implantation were included in this trial. There were 34 North American sites in the WATCH TAVR trial.
Participants by arm
| Arm | Count |
|---|---|
| TAVR + Medical Therapy n=175 will undergo Transcatheter Aortic Valve Replacement (TAVR) alone with medical management for atrial fibrillation
TAVR: Transcatheter Aortic Valve Replacement | 172 |
| TAVR + WATCHMAN n=175 will undergo simultaneous Transcatheter Aortic Valve Replacement (TAVR) with a WATCHMAN device.
WATCHMAN: WATCHMAN Device is composed of a self-expanding nitinol structure with a porous membrane on the proximal face. The implant device is delivered to the Left Atrial Appendage by femoral venous access and transseptal puncture to enter the left atrium.
TAVR: Transcatheter Aortic Valve Replacement | 177 |
| Total | 349 |
Baseline characteristics
| Characteristic | TAVR + WATCHMAN | Total | TAVR + Medical Therapy |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 177 Participants | 349 Participants | 172 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 80.8 years STANDARD_DEVIATION 7.8 | 81.1 years STANDARD_DEVIATION 7.2 | 81.5 years STANDARD_DEVIATION 6.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 173 Participants | 340 Participants | 167 Participants |
| Region of Enrollment United States | 177 Participants | 349 Participants | 172 Participants |
| Sex: Female, Male Female | 69 Participants | 135 Participants | 66 Participants |
| Sex: Female, Male Male | 108 Participants | 214 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 39 / 172 | 37 / 177 |
| other Total, other adverse events | 131 / 172 | 127 / 177 |
| serious Total, serious adverse events | 90 / 172 | 87 / 177 |
Outcome results
Primary
Composite of All-cause Mortality, Stroke and Bleeding
First occurrence of all-cause mortality, stroke (ischemic or hemorrhagic), or bleeding (life-threatening and major) events through 2 years post-randomization.
Time frame: Through 2 year post-randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAVR + Medical Therapy | Composite of All-cause Mortality, Stroke and Bleeding | 60 Participants |
| TAVR + WATCHMAN | Composite of All-cause Mortality, Stroke and Bleeding | 64 Participants |
Secondary
All-cause Mortality
All deaths through 2 year
Time frame: Through 2 year post-randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAVR + Medical Therapy | All-cause Mortality | 39 Participants |
| TAVR + WATCHMAN | All-cause Mortality | 37 Participants |
Secondary
Bleeding
First occurrence of any life-threatening or major bleeding through 2 year
Time frame: Through 2 year post-randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAVR + Medical Therapy | Bleeding | 30 Participants |
| TAVR + WATCHMAN | Bleeding | 35 Participants |
Secondary
Stroke
First occurrence of any ischemic or hemorrhagic stroke through 2 year
Time frame: Through 2 year post-randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAVR + Medical Therapy | Stroke | 12 Participants |
| TAVR + WATCHMAN | Stroke | 10 Participants |
Other Pre-specified
Cardiovascular Mortality
Cardiovascular related mortality through 2 year
Time frame: Through 2 year post-randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAVR + Medical Therapy | Cardiovascular Mortality | 22 Participants |
| TAVR + WATCHMAN | Cardiovascular Mortality | 20 Participants |
Other Pre-specified
Procedural Costs
Procedural costs related to the initial TAVR and WATCHMAN procedures
Time frame: Mean cost during hospitalization up to 40 days.
Population: Sites willing to provide cost data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAVR + Medical Therapy | Procedural Costs | 195309.64 dollars | Standard Deviation 206704.69 |
| TAVR + WATCHMAN | Procedural Costs | 216020.41 dollars | Standard Deviation 91603.542 |
Other Pre-specified
Quality of Life Score: KCCQ-12
Change from baseline in quality of life (QoL) as measured using the KCCQ-12 score. Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a validated tool used to assess heart failure and how it affects the participant's life. Four domain scores and one summary score are generated from the KCCQ-12: Physical Limitation Score, Symptom Frequency Score, Quality of Life Score, Social Limitation Score and a Summary Score. Scale ranges for each question 1 to 6 (Extremely limited 1, Quite a bit limited 2, Moderately limited 3, Slightly limited 4, Not at all limited 5, Limited for other reasons or did not do the activity 6. The Summary score represents an integration of the patient's physical limitation, symptom frequency, quality of life and social limitation. The total score is calculated as the average of the above scale descriptions. Scores are scaled 0-100, where 0 denotes the lowest reportable health status. Scores of 100 indicate the highest reportable health better outcome status.
Time frame: Through 2 year post-randomization
Population: Patient's with non missing KCCQ data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TAVR + Medical Therapy | Quality of Life Score: KCCQ-12 | KCCQ Questionnaire Score Visit 2- 45 Days | 55.2 score on a scale | Standard Deviation 17.77 |
| TAVR + Medical Therapy | Quality of Life Score: KCCQ-12 | KCCQ Questionnaire Score (Visit 4-12 Months) | 56.3 score on a scale | Standard Deviation 18.42 |
| TAVR + Medical Therapy | Quality of Life Score: KCCQ-12 | KCCQ Questionnaire Score (Visit 3- 6 Months) | 56.6 score on a scale | Standard Deviation 17.97 |
| TAVR + Medical Therapy | Quality of Life Score: KCCQ-12 | KCCQ Questionnaire Score (Visit 5- 24 months) | 57.1 score on a scale | Standard Deviation 18.99 |
| TAVR + Medical Therapy | Quality of Life Score: KCCQ-12 | KCCQ Questionnaire Score Visit 1-Baseline | 39.77 score on a scale | Standard Deviation 15.55 |
| TAVR + WATCHMAN | Quality of Life Score: KCCQ-12 | KCCQ Questionnaire Score (Visit 5- 24 months) | 57.0 score on a scale | Standard Deviation 16.51 |
| TAVR + WATCHMAN | Quality of Life Score: KCCQ-12 | KCCQ Questionnaire Score Visit 1-Baseline | 40.8 score on a scale | Standard Deviation 15.21 |
| TAVR + WATCHMAN | Quality of Life Score: KCCQ-12 | KCCQ Questionnaire Score Visit 2- 45 Days | 55.1 score on a scale | Standard Deviation 17.94 |
| TAVR + WATCHMAN | Quality of Life Score: KCCQ-12 | KCCQ Questionnaire Score (Visit 3- 6 Months) | 57.61 score on a scale | Standard Deviation 15.18 |
| TAVR + WATCHMAN | Quality of Life Score: KCCQ-12 | KCCQ Questionnaire Score (Visit 4-12 Months) | 57.4 score on a scale | Standard Deviation 15.67 |
Other Pre-specified
Re-hospitalization
Incidence of re-hospitalizations related to the WATCHMAN procedure or WATCHMAN device
Time frame: Through 2 year post-randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAVR + Medical Therapy | Re-hospitalization | 22 Participants |
| TAVR + WATCHMAN | Re-hospitalization | 18 Participants |
Other Pre-specified
Thrombus or Embolism
Incidence of arterial or venous embolism
Time frame: Through 2 year post-randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TAVR + Medical Therapy | Thrombus or Embolism | 3 Participants |
| TAVR + WATCHMAN | Thrombus or Embolism | 16 Participants |