Aortic Valve Stenosis
Conditions
Keywords
Lotus, Valve, Real world, Aortic stenosis, High risk
Brief summary
The purpose of the RESPOND post market study is to collect real world clinical and device performance outcomes data with the Lotus Valve System used in routine clinical practice to demonstrate that the commercially available Lotus Valve System is a safe and effective treatment for patients with severe calcific aortic stenosis.
Detailed description
The RESPOND study is a prospective, open label, single arm, multi-center, observational post market study designed to collect real world clinical and device performance outcomes data of the commercially available Lotus Valve used in routine clinical practice for the treatment of severe calcific aortic stenosis. Approximately 1000 real-world, consecutive subjects will be enrolled at up to 50 study centers in Europe, Asia Pacific and Central/South America. All enrolled subjects will be contacted for follow-up at 30 days, 1, 2, 3, 4 and 5 years post index valve implantation. Follow-up visit at 1 year post valve implantation should be conducted via outpatient clinic visit. Follow-up visits at 30 days and 2 through 5 years may be conducted in person (preferred) and via telephone interview. Subjects who are not implanted with a Lotus Valve will be followed for safety through 30 days after the initial attempted index procedure. Collection of safety events will include any serious adverse event (SAE) that led to death, serious adverse device effect (SADE), adverse device effect (ADE), unanticipated serious adverse device effect (USADE), and all Valve Academic Research Consortium (VARC) events regardless of seriousness and device relationship through 5 year follow-up. The RESPOND study will be conducted in accordance with the International Organization for Standardization (ISO) 14155: 2011; ethical principles that have their origins in the Declaration of Helsinki; the relevant parts of the International Conference on Harmonization (ICH) Guidelines for Good Clinical Practices (GCP); and pertinent individual country/state/local laws and regulations. An additional cohort of approximately 50 subjects will be enrolled at up to 6 study centers in Europe after enrollment in the main cohort is completed to assess center-driven implantation technique with the commercially available Lotus Valve with Depth Guard technology.
Interventions
DEVICELotus Valve System
The Lotus Valve System is indicated to improve aortic valve function for symptomatic subjects with severe calcific aortic stenosis (aortic valve area \[AVA\] of \<1.0 cm2 or index of \<0.6 cm2/m2) who are at high risk for standard surgical valve replacement.
Sponsors
Boston Scientific Corporation
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Subjects will be evaluated for eligibility by the clinical center's heart team per the local standard of practice in accordance with the Directions for Use.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality | 30 Days | The primary endpoint is all-cause mortality at 30 days after the implant procedure. The primary safety endpoint will be evaluated on an intention-to-treat (ITT) basis (all subjects enrolled, whether or not a Lotus Valve is implanted). All-cause mortality at 30 days after the implant procedure will be compared to a pre-specified performance goal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In-hospital Mortality | Duration of hospital stay, an expected average of 2 days | In-hospital mortality till discharge |
| Percentage of Participants With Events Included in the VARC Efficacy Composite Endpoint | 1 Year | The VARC efficacy composite at 1 year, including all-cause mortality; all stroke (disabling and non-disabling); re-hospitalization for valve-related symptoms or worsening congestive heart failure (NYHA class III or IV); and prosthetic valve-related dysfunction (mean aortic valve gradient ≥20 mmHg, effective orifice area (EOA) ≤0.9-1.1 cm2 and/or Doppler velocity index (DVI) \<0.35 m/s, AND/OR moderate or severe prosthetic valve aortic regurgitation) |
| Percentage of Participants With Events Included in the Safety Composite Endpoint of All-Cause Mortality and Disabling Stroke | 30 Days and 1 year | All subjects who are candidates for transcatheter aortic valve implantation (TAVI), signed the Informed Consent Form (ICF) and are selected to receive a Lotus Valve will be evaluated for enrollment in this study (as treated population) The Lotus Valve cohort is an ongoing study in it's 4 year follow up. The Lotus with Depth Guard cohort ended after 30 day follow up, therefore we have no data at 1 year. |
| Patients With VARC Safety Composite Outcomes at 30 Days | 30 Days | Patients with VARC safety composite outcomes at 30 days. VARC safety composite endpoints are defined as: * Life-threatening bleeding * Acute kidney injury-Stage 2 or 3 (including renal replacement therapy) * Coronary artery obstruction requiring intervention * Major vascular complication * Valve-related dysfunction requiring repeat procedure (BAV, TAVI, or SAVR) * New conduction disturbances (LBBB, AVB, RBBB) and need for permanent pacemaker implantation |
| Patients With Moderate and Severe Paravalvular Aortic Valve Regurgitation | Duration of hospital stay, an expected average of 2 days | Grade of paravalvular aortic valve regurgitation pre-discharge as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory. The moderate and severe paravalvular aortic regurgitation rate will be compared to a pre-specified performance goal. We don't have a powered analysis for the PVL for RESPOND study. |
| Patients With Valve Safety Composite Outcomes at 1 Year | 1 Year | Time related valve safety composite outcomes at 1 year, including structural valve deterioration (valve-related dysfunction requiring repeat procedure \[TAVI or SAVR\]); prosthetic valve endocarditis; prosthetic valve thrombosis; thromboembolic events (e.g. stroke) and VARC bleeding, unless clearly unrelated to valve therapy based on investigator assessment (e.g. trauma). The Lotus Valve cohort is an ongoing study in it's 4 year follow up. The Lotus with Depth Guard cohort ended after 30 day follow up, therefore we have no data at 1 year. |
Countries
Colombia, Finland, Germany, Israel, Italy, Netherlands, New Zealand, Norway, Poland, Spain, Sweden, Switzerland, United Kingdom
Participant flow
Recruitment details
There were 1014 subjects enrolled at 41 centers in Germany, UK, Italy, Colombia, Finland, The Netherlands, Poland, Spain, Israel, New Zealand, Norway, Sweden and Switzerland between 27 May 2014 and 01 Feb 2016. 50 subjects were enrolled in the cohort with the Lotus Depth Guard valve between 13 Jun 2016 and 31 Oct 2016.
Pre-assignment details
Lotus Valve cohort: 1 subject had the 1 year visit on 25SEP2015, but died on 02OCT2015, that's why the disposition table only shows 115 subjects died prior to 1 year Follow-up performed . A total of 116 subjects died through 1 year (365 days) post procedure (as treated population). 120 of 1002 patients died according to the ITT population.
Participants by arm
| Arm | Count |
|---|---|
| Lotus Valve All subjects who are candidates for Transcatheter Aortic Valve Implantation (TAVI), signed the Informed Consent Form (ICF) and are selected to receive a Lotus Valve.
Lotus Valve System: The Lotus Valve System is indicated to improve aortic valve function for symptomatic subjects with severe calcific aortic stenosis (aortic valve area \[AVA\] of \<1.0 cm2 or index of \<0.6 cm2/m2) who are at high risk for standard surgical valve replacement. | 996 |
| Lotus With Depth Guard All subjects who are candidates for Transcatheter Aortic Valve Implantation (TAVI), signed the Informed Consent Form (ICF) and are selected to receive a Lotus with Depth Guard.
Lotus Valve System: The Lotus Valve System is indicated to improve aortic valve function for symptomatic subjects with severe calcific aortic stenosis (aortic valve area \[AVA\] of \<1.0 cm2 or index of \<0.6 cm2/m2) who are at high risk for standard surgical valve replacement. | 50 |
| Total | 1,046 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 115 | 0 |
| Overall Study | Lost to Follow-up | 4 | 0 |
| Overall Study | Missed Follow Up | 27 | 0 |
| Overall Study | Not treated with study valve system | 18 | 0 |
Baseline characteristics
| Characteristic | Lotus Valve | Lotus With Depth Guard | Total |
|---|---|---|---|
| Age, Continuous | 80.8 years STANDARD_DEVIATION 6.5 | 80.9 years STANDARD_DEVIATION 8.2 | 80.8 years STANDARD_DEVIATION 6.6 |
| European System for Cardiac Operative Risk Evaluation (EuroSCORE 2011) | 8.0 units on a scale STANDARD_DEVIATION 8.4 | 3.3 units on a scale STANDARD_DEVIATION 1.7 | 7.8 units on a scale STANDARD_DEVIATION 8.2 |
| New York Heart Association (NYHA) Classification Not done | 71 participants | 1 participants | 72 participants |
| New York Heart Association (NYHA) Classification NYHA I | 34 participants | 1 participants | 35 participants |
| New York Heart Association (NYHA) Classification NYHA II | 248 participants | 22 participants | 270 participants |
| New York Heart Association (NYHA) Classification NYHA III | 577 participants | 25 participants | 602 participants |
| New York Heart Association (NYHA) Classification NYHA IV | 66 participants | 1 participants | 67 participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 506 Participants | 23 Participants | 529 Participants |
| Sex: Female, Male Male | 490 Participants | 27 Participants | 517 Participants |
| Society of Thoracic Surgeons (STS) Risk Score | 6.0 units on a scale STANDARD_DEVIATION 6.9 | 4.4 units on a scale STANDARD_DEVIATION 3.1 | 5.9 units on a scale STANDARD_DEVIATION 6.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 22 / 987 | 116 / 988 | 0 / 50 |
| other Total, other adverse events | 96 / 1,014 | 99 / 1,014 | 7 / 50 |
| serious Total, serious adverse events | 426 / 1,014 | 525 / 1,014 | 14 / 50 |
Outcome results
Primary
All-cause Mortality
The primary endpoint is all-cause mortality at 1 year after the implant procedure. The primary safety endpoint will be evaluated on an intention-to-treat (ITT) basis (all subjects enrolled, whether or not a Lotus Valve is implanted). A total of 116 subjects died through 1 year (365 days) post procedure (as treated population). 4 additional patients died but were not treated with the study valve system (ITT population). The Lotus Valve cohort is an ongoing study in it's 4 year follow up. The Lotus with Depth Guard cohort ended after 30 day follow up, therefore we have no data at 1 year.
Time frame: 1 Year
Population: The primary endpoint analysis is based on the ITT population (1014) through 1 year; 12 subjects out of 1014 subjects are excluded from the analysis because they don't have sufficient follow up, their last follow up days are less than 320 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lotus Valve | All-cause Mortality | 120 Participants |
Primary
All-cause Mortality
The primary endpoint is all-cause mortality at 30 days after the implant procedure. The primary safety endpoint will be evaluated on an intention-to-treat (ITT) basis (all subjects enrolled, whether or not a Lotus Valve is implanted). All-cause mortality at 30 days after the implant procedure will be compared to a pre-specified performance goal.
Time frame: 30 Days
Population: The primary endpoint analysis is based on the ITT population (1014) through 30 days; 9 subjects out of 1014 subjects are excluded from the analysis because they don't have sufficient follow up, their last follow up days are less than 23 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lotus Valve | All-cause Mortality | 26 Participants |
| Lotus With Depth Guard | All-cause Mortality | 0 Participants |
Comparison: Note: the 95% CI is from Clopper-Pearson Exact Method. The analysis was only done for the Lotus valve arm as the Lotus with Depth Guard arm has not sufficient power for this statistical analysis.p-value: <0.0001Chi-squared
Secondary
In-hospital Mortality
In-hospital mortality till discharge
Time frame: Duration of hospital stay, an expected average of 2 days
Population: The In-hospital till discharge analysis is based on the as treated population for the Lotus valve arm (996). In the Lotus with Depth Guard arm are all patients treated with the device.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lotus Valve | In-hospital Mortality | 18 Participants |
| Lotus With Depth Guard | In-hospital Mortality | 0 Participants |
Secondary
Patients With Moderate and Severe Paravalvular Aortic Valve Regurgitation
Grade of paravalvular aortic valve regurgitation pre-discharge as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory. The moderate and severe paravalvular aortic regurgitation rate will be compared to a pre-specified performance goal. We don't have a powered analysis for the PVL for RESPOND study.
Time frame: Duration of hospital stay, an expected average of 2 days
Population: 62 patients had no data available for the analysis in the Lotus Valve arm. 13 patients had no data for the analysis in the Lotus with Depth Guard arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lotus Valve | Patients With Moderate and Severe Paravalvular Aortic Valve Regurgitation | 179 Participants |
| Lotus With Depth Guard | Patients With Moderate and Severe Paravalvular Aortic Valve Regurgitation | 13 Participants |
Secondary
Patients With Valve Safety Composite Outcomes at 1 Year
Time related valve safety composite outcomes at 1 year, including structural valve deterioration (valve-related dysfunction requiring repeat procedure \[TAVI or SAVR\]); prosthetic valve endocarditis; prosthetic valve thrombosis; thromboembolic events (e.g. stroke) and VARC bleeding, unless clearly unrelated to valve therapy based on investigator assessment (e.g. trauma). The Lotus Valve cohort is an ongoing study in it's 4 year follow up. The Lotus with Depth Guard cohort ended after 30 day follow up, therefore we have no data at 1 year.
Time frame: 1 Year
Population: The analysis of patients with valve safety composite outcomes at 1 year is based on the as treated population for the Lotus valve arm (996) through 1 year; 8 subjects out of 996 subjects are excluded from the analysis because they don't have sufficient follow up; their last follow up days are less than 320 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lotus Valve | Patients With Valve Safety Composite Outcomes at 1 Year | 219 Participants |
Secondary
Patients With VARC Safety Composite Outcomes at 30 Days
Patients with VARC safety composite outcomes at 30 days. VARC safety composite endpoints are defined as: * Life-threatening bleeding * Acute kidney injury-Stage 2 or 3 (including renal replacement therapy) * Coronary artery obstruction requiring intervention * Major vascular complication * Valve-related dysfunction requiring repeat procedure (BAV, TAVI, or SAVR) * New conduction disturbances (LBBB, AVB, RBBB) and need for permanent pacemaker implantation
Time frame: 30 Days
Population: The analysis of patients with valve safety composite outcomes at 30 days based on the as treated population for the Lotus valve arm (996) through 30 days. In the Lotus with Depth Guard arm are all patients treated with the device.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lotus Valve | Patients With VARC Safety Composite Outcomes at 30 Days | 334 Participants |
| Lotus With Depth Guard | Patients With VARC Safety Composite Outcomes at 30 Days | 10 Participants |
Secondary
Percentage of Participants With Events Included in the Safety Composite Endpoint of All-Cause Mortality and Disabling Stroke
All subjects who are candidates for transcatheter aortic valve implantation (TAVI), signed the Informed Consent Form (ICF) and are selected to receive a Lotus Valve will be evaluated for enrollment in this study (as treated population) The Lotus Valve cohort is an ongoing study in it's 4 year follow up. The Lotus with Depth Guard cohort ended after 30 day follow up, therefore we have no data at 1 year.
Time frame: 30 Days and 1 year
Population: The Safety composite of all-cause mortality and disabling stroke analysis is based on the as treated population for the Lotus valve arm (996) through 1 year; 8 subjects out of 996 subjects are excluded from the analysis because they don't have sufficient follow up; their last follow up days are less than 320 days.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lotus Valve | Percentage of Participants With Events Included in the Safety Composite Endpoint of All-Cause Mortality and Disabling Stroke | 30 day outcome | 41 Participants |
| Lotus Valve | Percentage of Participants With Events Included in the Safety Composite Endpoint of All-Cause Mortality and Disabling Stroke | 1 year outcome | 135 Participants |
| Lotus With Depth Guard | Percentage of Participants With Events Included in the Safety Composite Endpoint of All-Cause Mortality and Disabling Stroke | 30 day outcome | 1 Participants |
| Lotus With Depth Guard | Percentage of Participants With Events Included in the Safety Composite Endpoint of All-Cause Mortality and Disabling Stroke | 1 year outcome | 0 Participants |
Secondary
Percentage of Participants With Events Included in the VARC Efficacy Composite Endpoint
The VARC efficacy composite at 1 year, including all-cause mortality; all stroke (disabling and non-disabling); re-hospitalization for valve-related symptoms or worsening congestive heart failure (NYHA class III or IV); and prosthetic valve-related dysfunction (mean aortic valve gradient ≥20 mmHg, effective orifice area (EOA) ≤0.9-1.1 cm2 and/or Doppler velocity index (DVI) \<0.35 m/s, AND/OR moderate or severe prosthetic valve aortic regurgitation)
Time frame: 1 Year
Population: The Lotus Valve cohort is an ongoing study in it's 4 year follow up. The Lotus with Depth Guard cohort ended after 30 day follow up, therefore we have no data at 1 year. 443 patients had no Echo analysis and therefore no data available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lotus Valve | Percentage of Participants With Events Included in the VARC Efficacy Composite Endpoint | 200 Participants |