Transcatheter Aortic Valve Replacement
Conditions
Brief summary
The purpose of this study is to evaluate the safety and performance of the Lotus™ Valve System for transcatheter aortic valve replacement (TAVR) in symptomatic subjects with severe calcific aortic stenosis who are considered high risk for surgical valve replacement.
Detailed description
The REPRISE II clinical study is a prospective, single-arm, multicenter study designed to evaluate the safety and performance of the Lotus Valve System for TAVR in symptomatic subjects who have severe calcific aortic valve stenosis and who are at high risk for surgical aortic valve replacement (SAVR).
Interventions
DEVICELotus Valve System
* bioprosthetic bovine pericardial aortic valve * delivery system
Sponsors
Boston Scientific Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is ≥70 years of age * Subject has documented calcific native aortic valve stenosis * Subject has a documented aortic annulus size between ≥19 and ≤27 mm based on pre-procedure diagnostic imaging * Symptomatic aortic valve stenosis with NYHA Functional Class ≥ II * Subject is considered high risk for surgical valve replacement * Heart team assessment that the subject is likely to benefit from valve replacement. * Subject (or legal representative) understands the study requirements and the treatment procedures, and provides written informed consent. * Subject, family member, and/or legal representative agree(s) and subject is capable of returning to the study hospital for all required scheduled follow up visits.
Exclusion criteria
* Subject has a congenital unicuspid or bicuspid aortic valve. * Subject with an acute myocardial infarction within 30 days of the index procedure * Subject has had a cerebrovascular accident or transient ischemic attack within the past 6 months, or has any permanent neurologic defect prior to study enrollment. * Subject is on dialysis or has serum creatinine level \>3.0 mg/dL or 265 µmol/L. * Subject has a pre-existing prosthetic heart valve (aortic or mitral) or a prosthetic ring in any position. * subject cannot have more than moderate mitral, aortic or tricuspid regurgitation * Subject has a need for emergency surgery for any reason. * Subject has a history of endocarditis within 12 months of index procedure or evidence of an active systemic infection or sepsis. * Subject has echocardiographic evidence of intra-cardiac mass, thrombus or vegetation. * Subject has low Hgb, platelet count or \>700,000 cells/mm3, or low white blood cell count. * Subject requires chronic anticoagulation therapy and cannot tolerate concomitant therapy with either aspirin or clopidogrel/ticlopidine * Subject has active peptic ulcer disease or gastrointestinal bleed within the past 3 months, other bleeding diathesis or coagulopathy or will refuse transfusions. * Subject has known hypersensitivity to contrast agents that cannot be adequately pre-medicated, or has known hypersensitivity to aspirin, all thienopyridines, heparin, nickel, tantalum, titanium, or polyurethanes. * Subject has a life expectancy of less than 12 months due to non-cardiac, co-morbid conditions based on the assessment of the investigator at the time of enrollment. * Subject has hypertrophic obstructive cardiomyopathy. * Subject has any therapeutic invasive cardiac procedure within 30 days prior to the index procedure (except for pacemaker implantation which is allowed). * Subject has untreated coronary artery disease. * Subject has documented left ventricular ejection fraction \<30%. * Subject is in cardiogenic shock or has hemodynamic instability requiring inotropic support or mechanical support devices. * Subject has severe peripheral vascular disease or symptomatic carotid or vertebral disease. * Narrow Femoral artery lumen precludes the use of either Lotus device size, or severe iliofemoral tortuosity or calcification that would prevent safe placement of the introducer sheath. * Current problems with substance abuse (e.g., alcohol, etc.). * Subject is participating in another investigational drug or device study that has not reached its primary endpoint. * Patient has preexisting untreated conduction system disorder that requires new pacemaker implantation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Device Performance Endpoint: Mean Aortic Valve Pressure Gradient at 30 Days Post Implant Procedure | 30 days | Mean aortic valve pressure gradient at 30 days post implant procedure as measured by echocardiography and assessed by an independent core laboratory. |
| Primary Safety Endpoint: All-cause Mortality at 30 Days Post Implant Procedure | 30 days | Mortality at 30 days from all patients enrolled in the study (ITT population): the proportion of patients who experience an event through 30 days post-procedure out of the patients who have either had an event within 30 days post-procedure or who were event-free with last follow-up at least 23 days post-procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Device Performance Endpoint: Successful Retrieval | Post-procedure | Successful retrieval (complete resheathing of the Lotus valve in the catheter and removal from the body) of the Lotus Valve System if retrieval is attempted, as reported from site |
| Device Performance Endpoint: Successful Repositioning | Post-procedure | Successful repositioning (partial or complete resheathing of the Lotus Valve in the catheter and redeployment in a more accurate position within the aortic valve annulus) of the Lotus Valve System if repositioning is attempted for the last valve attempted, as reported from site |
| Effective Orifice Area | 30 days | Effective orifice area measured by echocardiography at 30 days and assessed by an independent core laboratory (ITT population) |
| Grade of Aortic Valve Regurgitation | 30 days | Grade of paravalvular aortic valve regurgitation at 30 days as measured by echocardiography and assessed by an independent core laboratory |
| Device Success According to the Valve Academic Research Consortium (VARC) | Post-procedure | Absence of procedural mortality as reported from site AND Correct positioning of a single prosthetic heart valve into the proper anatomical location as reported from site AND Intended performance of the prosthetic heart valve (no prosthesis-patient mismatch and mean aortic valve gradient \<20 mmHg or peak velocity \<3 m/s, AND no moderate or severe prosthetic valve regurgitation as measured from an independent core lab on the post-procedure echocardiography) |
| Device Performance Endpoint: Successful Vascular Access | Post-procedure | Successful vascular access, delivery and deployment of the Lotus Valve System and successful retrieval of the delivery system as reported from site |
Countries
Australia, France, Germany, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| REPRISE II and Extension Overall Transcatheter aortic valve replacement (TAVR) with the Lotus™ Valve System.
Lotus Valve System: - bioprosthetic bovine pericardial aortic valve
\- delivery system | 250 |
| Total | 250 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 11 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Missed the visit | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | REPRISE II and Extension Overall |
|---|---|
| Age, Continuous | 84.0 years STANDARD_DEVIATION 5.2 |
| EuroSCORE | 6.4 percent predicted mortality STANDARD_DEVIATION 6.2 |
| NYHA Functional Class Grade I | 0 Participants |
| NYHA Functional Class Grade II | 57 Participants |
| NYHA Functional Class Grade III | 166 Participants |
| NYHA Functional Class Grade IV | 27 Participants |
| Race/Ethnicity, Customized Unknown or not reported | 250 Participants |
| Region of Enrollment Australia | 74 Participants |
| Region of Enrollment Europe | 171 Participants |
| Sex: Female, Male Female | 131 Participants |
| Sex: Female, Male Male | 119 Participants |
| STS Score | 6.5 units on a scale STANDARD_DEVIATION 4.2 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 250 |
| other Total, other adverse events | 157 / 250 |
| serious Total, serious adverse events | 152 / 250 |
Outcome results
Primary
Primary Device Performance Endpoint: Mean Aortic Valve Pressure Gradient at 30 Days Post Implant Procedure
Mean aortic valve pressure gradient at 30 days post implant procedure as measured by echocardiography and assessed by an independent core laboratory.
Time frame: 30 days
Population: As specified, this endpoint was evaluated using data from the first 120 patients enrolled in the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REPRISE II and Extension Overall | Primary Device Performance Endpoint: Mean Aortic Valve Pressure Gradient at 30 Days Post Implant Procedure | 11.45 mmHG | Standard Deviation 5.2 |
Primary
Primary Safety Endpoint: All-cause Mortality at 30 Days Post Implant Procedure
Mortality at 30 days from all patients enrolled in the study (ITT population): the proportion of patients who experience an event through 30 days post-procedure out of the patients who have either had an event within 30 days post-procedure or who were event-free with last follow-up at least 23 days post-procedure
Time frame: 30 days
Population: Mortality at 30 days from all patients enrolled in the study (ITT population): the proportion of patients who experience an event through 30 days post-procedure out of the patients who have either had an event within 30 days post-procedure or who were event-free with last follow-up at least 23 days post-procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPRISE II and Extension Overall | Primary Safety Endpoint: All-cause Mortality at 30 Days Post Implant Procedure | 11 Participants |
Secondary
Device Performance Endpoint: Successful Repositioning
Successful repositioning (partial or complete resheathing of the Lotus Valve in the catheter and redeployment in a more accurate position within the aortic valve annulus) of the Lotus Valve System if repositioning is attempted for the last valve attempted, as reported from site
Time frame: Post-procedure
Population: Number of participants for whom a repositioning of the valve was attempted
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPRISE II and Extension Overall | Device Performance Endpoint: Successful Repositioning | 85 Participants |
Secondary
Device Performance Endpoint: Successful Retrieval
Successful retrieval (complete resheathing of the Lotus valve in the catheter and removal from the body) of the Lotus Valve System if retrieval is attempted, as reported from site
Time frame: Post-procedure
Population: Number of participants for whom a retrieval of the valve was attempted
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPRISE II and Extension Overall | Device Performance Endpoint: Successful Retrieval | 12 Participants |
Secondary
Device Performance Endpoint: Successful Vascular Access
Successful vascular access, delivery and deployment of the Lotus Valve System and successful retrieval of the delivery system as reported from site
Time frame: Post-procedure
Population: ITT population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPRISE II and Extension Overall | Device Performance Endpoint: Successful Vascular Access | 247 Participants |
Secondary
Device Success According to the Valve Academic Research Consortium (VARC)
Absence of procedural mortality as reported from site AND Correct positioning of a single prosthetic heart valve into the proper anatomical location as reported from site AND Intended performance of the prosthetic heart valve (no prosthesis-patient mismatch and mean aortic valve gradient \<20 mmHg or peak velocity \<3 m/s, AND no moderate or severe prosthetic valve regurgitation as measured from an independent core lab on the post-procedure echocardiography)
Time frame: Post-procedure
Population: Number of patients who had an echocardiography available post-procedure for the Core Lab to measure the performance of the prosthetic heart valve as described above
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| REPRISE II and Extension Overall | Device Success According to the Valve Academic Research Consortium (VARC) | 96 Participants |
Secondary
Effective Orifice Area
Effective orifice area measured by echocardiography at 30 days and assessed by an independent core laboratory (ITT population)
Time frame: 30 days
Population: Patients with an echocardiography available from the 30-day follow-up visit and analyzable by the Core Lab
| Arm | Measure | Value (MEAN) |
|---|---|---|
| REPRISE II and Extension Overall | Effective Orifice Area | 1.73 square centimeter |
Secondary
Grade of Aortic Valve Regurgitation
Grade of paravalvular aortic valve regurgitation at 30 days as measured by echocardiography and assessed by an independent core laboratory
Time frame: 30 days
Population: Patients with echocardiography available from the 30-day follow-up visit and analyzable from the Core Lab for those measurements
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| REPRISE II and Extension Overall | Grade of Aortic Valve Regurgitation | Trace/Trivial | 18 Participants |
| REPRISE II and Extension Overall | Grade of Aortic Valve Regurgitation | None | 159 Participants |
| REPRISE II and Extension Overall | Grade of Aortic Valve Regurgitation | Mild | 31 Participants |
| REPRISE II and Extension Overall | Grade of Aortic Valve Regurgitation | Mild-moderate | 0 Participants |
| REPRISE II and Extension Overall | Grade of Aortic Valve Regurgitation | Moderate | 1 Participants |
| REPRISE II and Extension Overall | Grade of Aortic Valve Regurgitation | Moderate-Severe | 0 Participants |
| REPRISE II and Extension Overall | Grade of Aortic Valve Regurgitation | Severe | 0 Participants |
| REPRISE II and Extension Overall | Grade of Aortic Valve Regurgitation | Severity not evaluable | 1 Participants |