Stroke
Conditions
Keywords
Non-valvular Atrial Fibrillation, Left Atrial Appendage
Brief summary
The WAVECREST 2 trial is a prospective, multicenter, randomized, active controlled, clinical trial to evaluate the safety and effectiveness of the Coherex WaveCrest Left Atrial Appendage (LAA) Occlusion System.
Detailed description
The WAVECREST 2 trial is a prospective, multicenter, randomized, active controlled, clinical trial to evaluate the safety and effectiveness of the Coherex WaveCrest Left Atrial Appendage (LAA) Occlusion System. Subjects will be randomized in a 1:1 ratio to the Treatment Arm (Coherex WaveCrest LAA occlusion system) or the Control Arm (Boston Scientific's Watchman LAA occlusion system). The trial is designed to demonstrate that safety and effectiveness of the WaveCrest device are non-inferior to the Watchman device.
Interventions
DEVICECoherex WaveCrest® Left Atrial Appendage Occlusion System
Percutaneous left atrial appendage closure
DEVICEWatchman® LAA Closure Device
Percutaeous left atrial appendage closure
Sponsors
Biosense Webster, Inc.
Coherex Medical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
If the subject is suspected of having a stroke since their most recent follow-up, a Neurologist blinded to subject's randomization and implanted device must evaluate the subject or otherwise provide rationale for why an in-person neurology visit and exam are unnecessary. Neurology or blinded trial personnel should also administer mRS & NIHSS if there is suspicion of stroke A Clinical Events Committee, also blinded to subject's randomization, will adjudicate primary safety and effectiveness.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Documented evidence of paroxysmal, persistent, or permanent non-valvular atrial fibrillation 2. At least 18 years of age 3. Calculated CHADS2 score ≥ 2 or CHA2DS2-VASc score ≥ 3 4. Indication for warfarin therapy with an appropriate rationale to seek a non-pharmacologic alternative to chronic oral anticoagulation 5. Willing and able to comply with post-implant anticoagulation and antiplatelet regimen 6. Willing to participate in the required follow-up visits and tests 7. Subject has been informed of the nature of the trial, agrees to its provisions and has provided written informed consent as approved by the IRB/EC at the site
Exclusion criteria
1. Atrial fibrillation (AF) due to a reversible cause (e.g. thyrotoxicosis or postoperative) 2. Known contraindication and/or allergy to warfarin, nickel, aspirin, intravenous contrast or P2Y12 inhibitors (clopidogrel, ticagrelor, and prasugrel), which cannot be adequately pre-medicated or desensitized 3. Conditions other than AF requiring long-term anticoagulation therapy 4. Contraindications for percutaneous catheterization procedures 5. Prior surgical LAA occlusion/exclusion or implanted with LAA occlusion device, or any prior attempt of such procedures 6. Prior percutaneous or surgical closure of a patent foramen ovale or atrial septal defect 7. Inability or unwillingness to take oral anticoagulation for 45 days post-procedure 8. New York Heart Association (NYHA) Class IV heart failure 9. Prior cardiac transplant, history of mitral valve replacement or transcatheter mitral valve intervention, or any mechanical valve implant 10. History of symptomatic carotid, intervertebral, or intracranial artery occlusion or stenosis without revascularization with the exception of known occlusion without symptoms \> 6 months 11. Modified Rankin Scale (mRS) score ≥ 4 12. Chronic resting heart rate ≥ 110 bpm 13. Congenital cardiac anomalies requiring cardiac surgery or interventional repair 14. Stroke or transient ischemic attack (confirmed by Neurologist) within 60 days prior to enrollment 15. Myocardial infarction within 60 days prior to enrollment 16. Sepsis or any infection requiring oral antibiotic therapy within 14 days or intravenous antibiotic therapy within 30 days prior to enrollment 17. Surgical or interventional cardiovascular and non-cardiovascular procedure including cardioversion within 30 days prior to enrollment or AF ablation within 60 days prior to enrollment or any planned general surgery or interventional procedure within 90 days after enrollment or any planned cardiac surgery. 18. On renal replacement therapy, serum creatinine \> 3.0 mg/dl (265 μmol/L) or calculated creatinine clearance \< 25 ml/minute 19. Thrombocytopenia (\<60,000 platelets/mm3), leucopenia (white blood cell count \< 3,000 cells/mm³), or anemia (hemoglobin concentration \< 10 grams/deciliter) based on blood work done within 30 days prior to enrollment 20. Any medical disorder or psychiatric illness that would interfere with successful completion of the trial 21. Currently participating in an investigational drug trial or another device trial that has not completed the primary endpoint (trials requiring extended follow-up for products that are commercially available are not considered investigational trials). Concurrent enrollment in the ACC LAAO Registry is permitted. 22. Subject belongs to a vulnerable population (see definition in Appendix I: Acronyms and Definitions) 23. Any condition that would reduce life expectancy to less than 2 years 24. Women of childbearing potential who are, or plan to become pregnant during the time of the trial (method of assessment per physician discretion) Echocardiographic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Composite of All Cause Death, Procedure or Device Related Complications Requiring Percutaneous or Surgical Intervention or Major Bleeding | All death, procedure- or device-related complications requiring percutaneous or surgical intervention: From baseline up to 45 days; major bleeding: From baseline up to 5 years 11 months | The primary safety outcome was the composite of death from any cause (all-cause mortality), procedure or device related complications requiring percutaneous or surgical intervention through 45 days post procedure or major bleeding throughout the duration of the trial. The analysis was based on sponsor assessment of adverse events data. Baseline was defined as 90 day prior to treatment or 90 days prior to randomization; baseline assessments could occur on the day of implant. |
| Percentage of Participants With Composite of Ischemic Stroke or Systemic Embolism at 24 Months | At 24 months | Percentage of participants with composite of ischemic stroke or systemic embolism at 24 months was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Ischemic Stroke or Systemic Embolism With the WAVECREST Device in Comparison to the CHADS2 and CHA2DS2-VASc Imputed Risk of Ischemic Stroke or Systemic Embolism in the Absence of Anticoagulant Therapy | At 45 days | CHADS2 (congestive heart failure, hypertension, age \>=75 years (yrs), prior Stroke/transient ischemic attack (TIA)/Thromboembolism) and CHA2DS2-VASc scores (Vascular disease, Age 65- 74 yrs, female Sex) were developed to identify non-valvular atrial fibrillation (AF) participants at an elevated risk for ischemic stroke. CHADS2 score assign 1 point: congestive heart failure, hypertension, age \>= 75 yrs, diabetes mellitus; 2 points: prior stroke/TIA/thromboembolism. CHADS2 score ranges from 0 to 6. Higher scores indicated higher risk for ischemic strokes. CHA2DS2-VASc Score assign 1 point for each following risk factors: congestive heart failure, hypertension (blood pressure consistently above 140/90), diabetes mellitus, vascular disease, age 65 to74 yrs, female and assigned 2 points for age \>=75 yrs and prior stroke or TIA or thromboembolism each. Overall score ranged from 0 to a 9, with lower scores indicated lower risk and higher scores indicated higher risk for ischemic strokes. |
| Percentage of Participants With Left Atrial Appendage (LAA) Closure | At 45 days | Percentage of participants with LAA closure, defined as a gap of \<= 5 millimetre (mm) at the 45-day visit as assessed by transesophageal echocardiogram (TEE) was reported. |
Countries
Australia, United States
Participant flow
Recruitment details
Analysis population included participants greater than or equal to (\>=) 18 years old diagnosed with non-valvular atrial fibrillation and a CHADS2 score \>= 2 or a CHA2DS2-VASc score \>= 3 who had an appropriate rationale to seek a non-pharmacologic alternative to chronic oral anticoagulation.
Pre-assignment details
As pre-specified in the protocol, participants who signed the informed consent form (ICF) were considered enrolled in the study. Out of the 248 enrolled participants (who signed the ICF), 183 were randomized to respective treatment arms, 26 were screen failures and 39 discontinued due to study hold during the screening period. Hence, data for 183 randomized participants is reported below.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (WaveCrest Roll-In) Roll in participants who were enrolled prior to a site's randomization phase and who had vascular access attempted, underwent Coherex WaveCrest left atrial appendage (LAA) occlusion system (WaveCrest device) implant procedure. Coherex Wave Crest LAA occlusion system delivery sheath was used to deliver the implant percutaneously via the femoral vein through a transseptal puncture into the LAA. | 71 |
| Group 2 (WaveCrest Randomized) Randomized participants underwent Coherex WaveCrest LAA occlusion system (WaveCrest device) implant procedure. Coherex Wave Crest LAA occlusion system delivery sheath was used to deliver the implant percutaneously via the femoral vein through a trans septal puncture into the LAA. | 52 |
| Group 3 (Watchman Randomized) Randomized participants underwent Watchman left atrial appendage closure (LAAC) System (Watchman Device) implant procedure. Watchman device was intended for percutaneous, transcatheter closure of the left atrial appendage and consisted of the watchman access system (access sheath and dilator) and watchman delivery system (delivery catheter and watchman device). The access sheath and delivery catheter permitted device placement in the LAA via femoral venous access and inter-atrial septum crossing into the left atrium. | 56 |
| Total | 179 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 |
| Overall Study | Death | 13 | 11 | 4 |
| Overall Study | Lost to Follow-up | 1 | 3 | 3 |
| Overall Study | Other | 7 | 4 | 6 |
| Overall Study | Physician Decision | 1 | 0 | 1 |
| Overall Study | Randomized but not treated and discontinued during study hold | 0 | 2 | 2 |
| Overall Study | Study Terminated by Sponsor | 32 | 29 | 30 |
| Overall Study | Withdrawal by Subject | 10 | 2 | 9 |
Baseline characteristics
| Characteristic | Group 1 (WaveCrest Roll-In) | Group 2 (WaveCrest Randomized) | Group 3 (Watchman Randomized) | Total |
|---|---|---|---|---|
| Age, Continuous | 72.0 years STANDARD_DEVIATION 9.64 | 75.9 years STANDARD_DEVIATION 6.43 | 76.0 years STANDARD_DEVIATION 5.69 | 74.4 years STANDARD_DEVIATION 7.88 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 69 Participants | 51 Participants | 53 Participants | 173 Participants |
| Sex: Female, Male Female | 32 Participants | 21 Participants | 20 Participants | 73 Participants |
| Sex: Female, Male Male | 39 Participants | 31 Participants | 36 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 15 / 71 | 13 / 52 | 4 / 56 |
| other Total, other adverse events | 63 / 71 | 51 / 52 | 48 / 56 |
| serious Total, serious adverse events | 50 / 71 | 42 / 52 | 39 / 56 |
Outcome results
Primary
Percentage of Participants With Composite of All Cause Death, Procedure or Device Related Complications Requiring Percutaneous or Surgical Intervention or Major Bleeding
The primary safety outcome was the composite of death from any cause (all-cause mortality), procedure or device related complications requiring percutaneous or surgical intervention through 45 days post procedure or major bleeding throughout the duration of the trial. The analysis was based on sponsor assessment of adverse events data. Baseline was defined as 90 day prior to treatment or 90 days prior to randomization; baseline assessments could occur on the day of implant.
Time frame: All death, procedure- or device-related complications requiring percutaneous or surgical intervention: From baseline up to 45 days; major bleeding: From baseline up to 5 years 11 months
Population: The intention-to-treat (ITT) analysis set consisted of all randomized participants regardless of treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (WaveCrest Roll-In) | Percentage of Participants With Composite of All Cause Death, Procedure or Device Related Complications Requiring Percutaneous or Surgical Intervention or Major Bleeding | 47.89 Percentage of participants |
| Group 2 (WaveCrest Randomized) | Percentage of Participants With Composite of All Cause Death, Procedure or Device Related Complications Requiring Percutaneous or Surgical Intervention or Major Bleeding | 32.69 Percentage of participants |
| Group 3 (Watchman Randomized) | Percentage of Participants With Composite of All Cause Death, Procedure or Device Related Complications Requiring Percutaneous or Surgical Intervention or Major Bleeding | 17.86 Percentage of participants |
Primary
Percentage of Participants With Composite of Ischemic Stroke or Systemic Embolism at 24 Months
Percentage of participants with composite of ischemic stroke or systemic embolism at 24 months was reported.
Time frame: At 24 months
Population: The ITT analysis set consisted of all randomized participants regardless of treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (WaveCrest Roll-In) | Percentage of Participants With Composite of Ischemic Stroke or Systemic Embolism at 24 Months | 4.23 Percentage of participants |
| Group 2 (WaveCrest Randomized) | Percentage of Participants With Composite of Ischemic Stroke or Systemic Embolism at 24 Months | 3.85 Percentage of participants |
| Group 3 (Watchman Randomized) | Percentage of Participants With Composite of Ischemic Stroke or Systemic Embolism at 24 Months | 5.36 Percentage of participants |
Secondary
Percentage of Participants With Ischemic Stroke or Systemic Embolism With the WAVECREST Device in Comparison to the CHADS2 and CHA2DS2-VASc Imputed Risk of Ischemic Stroke or Systemic Embolism in the Absence of Anticoagulant Therapy
CHADS2 (congestive heart failure, hypertension, age \>=75 years (yrs), prior Stroke/transient ischemic attack (TIA)/Thromboembolism) and CHA2DS2-VASc scores (Vascular disease, Age 65- 74 yrs, female Sex) were developed to identify non-valvular atrial fibrillation (AF) participants at an elevated risk for ischemic stroke. CHADS2 score assign 1 point: congestive heart failure, hypertension, age \>= 75 yrs, diabetes mellitus; 2 points: prior stroke/TIA/thromboembolism. CHADS2 score ranges from 0 to 6. Higher scores indicated higher risk for ischemic strokes. CHA2DS2-VASc Score assign 1 point for each following risk factors: congestive heart failure, hypertension (blood pressure consistently above 140/90), diabetes mellitus, vascular disease, age 65 to74 yrs, female and assigned 2 points for age \>=75 yrs and prior stroke or TIA or thromboembolism each. Overall score ranged from 0 to a 9, with lower scores indicated lower risk and higher scores indicated higher risk for ischemic strokes.
Time frame: At 45 days
Population: The ITT analysis set consisted of all randomized participants regardless of treatment received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 (WaveCrest Roll-In) | Percentage of Participants With Ischemic Stroke or Systemic Embolism With the WAVECREST Device in Comparison to the CHADS2 and CHA2DS2-VASc Imputed Risk of Ischemic Stroke or Systemic Embolism in the Absence of Anticoagulant Therapy | ischemic strokes | 4.23 Percentage of participants |
| Group 1 (WaveCrest Roll-In) | Percentage of Participants With Ischemic Stroke or Systemic Embolism With the WAVECREST Device in Comparison to the CHADS2 and CHA2DS2-VASc Imputed Risk of Ischemic Stroke or Systemic Embolism in the Absence of Anticoagulant Therapy | systemic embolisms | 0 Percentage of participants |
| Group 2 (WaveCrest Randomized) | Percentage of Participants With Ischemic Stroke or Systemic Embolism With the WAVECREST Device in Comparison to the CHADS2 and CHA2DS2-VASc Imputed Risk of Ischemic Stroke or Systemic Embolism in the Absence of Anticoagulant Therapy | ischemic strokes | 3.85 Percentage of participants |
| Group 2 (WaveCrest Randomized) | Percentage of Participants With Ischemic Stroke or Systemic Embolism With the WAVECREST Device in Comparison to the CHADS2 and CHA2DS2-VASc Imputed Risk of Ischemic Stroke or Systemic Embolism in the Absence of Anticoagulant Therapy | systemic embolisms | 0 Percentage of participants |
| Group 3 (Watchman Randomized) | Percentage of Participants With Ischemic Stroke or Systemic Embolism With the WAVECREST Device in Comparison to the CHADS2 and CHA2DS2-VASc Imputed Risk of Ischemic Stroke or Systemic Embolism in the Absence of Anticoagulant Therapy | ischemic strokes | 5.36 Percentage of participants |
| Group 3 (Watchman Randomized) | Percentage of Participants With Ischemic Stroke or Systemic Embolism With the WAVECREST Device in Comparison to the CHADS2 and CHA2DS2-VASc Imputed Risk of Ischemic Stroke or Systemic Embolism in the Absence of Anticoagulant Therapy | systemic embolisms | 0 Percentage of participants |
Secondary
Percentage of Participants With Left Atrial Appendage (LAA) Closure
Percentage of participants with LAA closure, defined as a gap of \<= 5 millimetre (mm) at the 45-day visit as assessed by transesophageal echocardiogram (TEE) was reported.
Time frame: At 45 days
Population: Analysis population included all roll-in and randomized and treated participants. Here 'N' (number of participants analysed) signifies number of participants who were evaluable for this outcome measures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (WaveCrest Roll-In) | Percentage of Participants With Left Atrial Appendage (LAA) Closure | 100.0 Percentage of participants |
| Group 2 (WaveCrest Randomized) | Percentage of Participants With Left Atrial Appendage (LAA) Closure | 100.0 Percentage of participants |
| Group 3 (Watchman Randomized) | Percentage of Participants With Left Atrial Appendage (LAA) Closure | 100.0 Percentage of participants |