Aortic Valve Calcification, Aortic Valve Disease, Aortic Valve Stenosis
Conditions
Keywords
Aortic Valve Stenosis, Transcatheter Aortic Valve Replacement
Brief summary
This is a prospective, single-arm feasibility study designed to assess the acute safety and performance of the Lotus Valve System for transcatheter aortic valve replacement in symptomatic patients with calcified aortic valve stenosis and who are at high risk for surgical intervention.
Detailed description
The incidence of aortic stenosis is increasing due to the aging of the world-wide population and the lack of drug therapies to prevent, halt, or effectively slow the stenotic process. Transcatheter aortic valve replacement has become a viable alternative for treatment of severe symptomatic aortic stenosis in selected patients who are unsuitable candidates for surgical valve replacement. The Lotus Valve System is designed to enable precise placement and minimize or eliminate the paravalvular regurgitation and associated adverse events seen with earlier generation devices. The REPRISE I study assesses acute safety and performance.
Interventions
DEVICELotus Valve System
The Lotus Valve System includes the Lotus Valve, a bovine tissue tri-leaflet bioprosthetic aortic valve, and the Lotus Delivery Catheter for guidance and placement.
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
1. Patient must be at least 70 years of age or older, and meets all of the criteria below. 2. Patient has documented calcified native aortic valve stenosis, defined with an initial aortic valve area (AVA) of \<1.0 cm2 (or AVA index of \<0.6 cm2/m2), and a mean pressure gradient \>40 mmHg or a jet velocity \>4 m/s, as measured by echocardiography. 3. The patient is considered at high risk for surgical aortic valve replacement with an STS (Society of Thoracic Surgeons) score ≥8% or a EuroSCORE ≥20%, or documented multidisciplinary heart team agreement that the patient is at high risk for surgery due to frailty and/or coexisting comorbidities. 4. Symptomatic aortic valve stenosis with New York Heart Association (NYHA) Functional Class ≥ II. 5. Patient has a documented aortic annulus size between 19 and 22 mm (able to accommodate the 23 mm Lotus™ Valve). Pre-procedure measurement by transthoracic echocardiography (TTE) is required. Other imaging modalities (e.g., transesophageal echocardiography (TEE), CT scan) can be used in an adjunctive manner. 6. Patient (or legal representative) understands the trial requirements and the treatment procedures, and provides written informed consent. 7. Patient agrees and is capable of returning to the study hospital for all required scheduled follow up visits.
Exclusion criteria
1. Patient has a congenital unicuspid or bicuspid aortic valve. 2. Patient with an acute myocardial infarction (MI) within 30 days of the index procedure (defined as Q wave MI, or non-Q wave MI with total creatine kinase (CK) elevation ≥ twice normal in the presence of CK-MB elevation and/or troponin level elevation (WHO definition)). 3. Patient has had a cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the past 6 months, or has any permanent neurologic defect prior to study enrollment. 4. Patient is on dialysis or has serum creatinine level \>3.0 mg/dL. 5. Patient has a pre-existing prosthetic heart valve (aortic or mitral) or a prosthetic ring in any position. 6. Patient has \>2+ mitral regurgitation or \>2+ aortic regurgitation (ie., patient cannot have more than moderate mitral or aortic regurgitation). 7. Moderate to severe pulmonary hypertension (PA systolic pressure \>60 mm Hg) as assessed by transthoracic echocardiography. 8. Patient has a need for emergency surgery for any reason. 9. Patient has a history of endocarditis within 12 months of index procedure or evidence of an active systemic infection or sepsis. 10. Patient has echocardiographic evidence of intra-cardiac mass, thrombus or vegetation. 11. Patient has Hgb \<9 g/dL, platelet count \<100,000 cells/mm3 or \>700,000 cells/mm3, and white blood cell (WBC) count \<3,000 cells/mm3. 12. Patient is receiving chronic (≥72 hours) anticoagulation therapy (e.g., heparin, warfarin) and who cannot tolerate concomitant therapy with aspirin and clopidogrel (patients who require chronic anticoagulation must be treated with either aspirin or clopidogrel). 13. Patient has active peptic ulcer disease, gastrointestinal (GI) bleed within the past 3 months, other bleeding diathesis or coagulopathy or will refuse transfusions. 14. Patient is contraindicated for transesophageal echocardiography (TEE). 15. Patient has known hypersensitivity to contrast agents that cannot be adequately pre-medicated, or has known hypersensitivity to aspirin, all thienopyridines, heparin, nickel, titanium, or polyurethanes. 16. Patient 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. 17. Patient has other cardiac devices or hardware with which the study device will interfere with device placement (per physician judgment). 18. Patient has hypertrophic obstructive cardiomyopathy. 19. Patient has any therapeutic invasive cardiac procedure within 30 days prior to the index procedure. 20. Untreated clinically significant coronary artery disease requiring revascularization. 21. Patient has documented left ventricular ejection fraction (LVEF) \<30%. 22. Patient is in cardiogenic shock or has hemodynamic instability requiring inotropic support or mechanical support devices. 23. Patient has severe peripheral vascular disease (including aneurysm defined as maximal luminal diameter \>5cm or with documented presence of thrombus, marked tortuosity, narrowing of the abdominal aorta, severe unfolding of the thoracic aorta or thick (\>5mm), protruding or ulcerated atheroma in the aortic arch) or symptomatic carotid or vertebral disease. 24. Patient has a femoral artery lumen of \<6.0 mm or severe iliofemoral tortuosity or calcification that would prevent safe placement of the introducer sheath. 25. Current problems with substance abuse (e.g. alcohol, cocaine, heroin, etc). 26. Patient is participating in another investigational drug or device study that has not reached its primary endpoint. 27. Patient has preexisting untreated conduction system disorders: Type II second-degree atrioventricular (AV) block, bifascicular or trifascicular block.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Procedural Success | Discharge or 7 days post-procedure, whichever comes first | Clinical procedural success defined as successful implantation of a Lotus Valve System (Device Success) without in-hospital Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) through discharge or 7 days post-procedure, whichever comes first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Device Performance Endpoint-Repositioning | procedure | Successful repositioning of the Lotus Valve System if repositioning is attempted |
| Device Performance Endpoint-Valve Retrieval, if Attempted | procedure | Successful retrieval of the Lotus Valve System if retrieval is attempted |
| Central Aortic Regurgitation | Discharge or 7 days post-procedure, whichever comes first | As determined by echocardiography |
| Paravalvular Aortic Regurgitation | Discharge or 7 days post-procedure, whichever comes first | As determined by echocardiography |
Other
| Measure | Time frame | Description |
|---|---|---|
| Aortic Valve Area | Discharge or 7 days post-procedure, whichever comes first | As determined by echocardiography |
| Death | Discharge or 7 days post-procedure, whichever comes first | — |
| Peri-procedural Myocardial Infarction | 72 hours | Peri-Procedural Myocardial Infarction (≤72 hours after the index procedure) * New ischemic symptoms (e.g., chest pain or shortness of breath), or new ischemic signs (e.g. ventricular arrhythmias, new or worsening heart failure, new ST-segment changes, hemodynamic instability, or imaging evidence of new loss of viable myocardium or new wall motion abnormality), AND * Elevated cardiac biomarkers (preferably creatine kinase-myoglobin band) within 72 h after the index procedure, consisting of two or more post-procedure samples that are \> 0.6 to 8 h apart with a 20% increase in the second sample and a peak value exceeding 10X the 99th percentile upper reference limit (URL), or a peak value exceeding 5X the 99th percentile URL with new pathological Q waves in at least 2 contiguous leads |
| Major Stroke | Discharge or 7 days post-procedure, whichever comes first | Confirmed with a Modified Rankin score \>/= 2 at 30 and 90 days |
| Successful Access, Device Delivery, Deployment and Positioning and Retrieval of Delivery System | Procedure | — |
| Major Vascular Complication | Discharge or 7 days post-procedure, whichever comes first | * Any thoracic aortic dissection * Access site or access-related vascular injury (dissection, stenosis, perforation, rupture, arterio-venous fistula, pseudoaneurysm, hematoma, irreversible nerve injury, or compartment syndrome) leading to either death, need for significant blood transfusions (≥4 units), unplanned percutaneous or surgical intervention, or irreversible end-organ damage (e.g. hypogastric artery occlusion causing visceral ischemia or spinal artery injury causing neurologic impairment) * Distal embolization (non-cerebral) from a vascular source requiring surgery or resulting in amputation or irreversible end-organ damage |
| New Conduction Disturbances or Arrhythmias Requiring Permanent Pacemaker | Discharge or 7 days post-procedure, whichever comes first | — |
| Bleeding | Discharge or 7 days post-procedure, whichever comes first | Life-threatening or Disabling Bleeding * Fatal bleeding OR * Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome OR * Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery OR * Overt source of bleeding with drop in hemoglobin of ≥5 g/dL or whole blood or packed red blood cells (RBC) transfusion ≥4 units Major Bleeding * Overt bleeding either associated with a drop in the hemoglobin level of at least 3.0g/dL or requiring transfusion of 2 or 3 units of whole blood/RBC AND * Does not meet criteria of life-threatening or disabling bleeding |
| Acute Kidney Injury - Stage 2 or 3 | Discharge or 7 days post-procedure, whichever comes first | Stage 2: Increase in serum creatinine to 200-300% (2.0-3.0 times increase compared with baseline). Stage 3: Increase in serum creatinine to ≥ 300% (\> 3 times increase compared with baseline) or serum creatinine of ≥ 4.0 mg/d (≥ 354 μmol/L) with an acute increase of at least 0.5 mg/dl (44 μmol/L). Subjects receiving renal replacement therapy are considered to meet Stage 3 criteria irrespective of other criteria. |
| Urgent/Emergent Conversion to Surgery or Repeat Procedure for Valve-related Dysfunction | Discharge or 7 days post-procedure, whichever comes first | — |
| Intended Performance of the Lotus Valve | At time of discharge or 7 days post procedure | Aortic valve area \>1.0 cm2 plus either a mean aortic valve gradient \<20 mmHg or peak velocity \<3m/sec, without moderate or severe prosthetic valve aortic regurgitation |
| Single Valve Implanted in the Proper Anatomical Location | procedure | — |
| No Major Adverse Cardiovascular and Cerebrovascular Events Through Discharge | Discharge or 7 days post-procedure, whichever comes first | Major adverse cardiovascular or cerebrovascular events include all-cause mortality, periprocedural myocardial infarction ≤72 hours, major stroke, urgent/emergent conversion to surgery or repeat procedure for valve-related dysfunction |
| Mean Aortic Valve Gradient | Discharge or 7 days post-procedure, whichever comes first | As determined by echocardiography |
Countries
Australia
Participant flow
Recruitment details
Patients were identified by their physicians as meeting the study inclusion/exclusion criteria.
Pre-assignment details
Screening materials from patients identified by the investigators as having met the inclusion and exclusion criteria were reviewed by a Case Review Committee to assess and confirm eligibility.
Participants by arm
| Arm | Count |
|---|---|
| Lotus Valve System Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Lotus Valve System |
|---|---|
| 5-Meter Gait Speed | 8.2 seconds STANDARD_DEVIATION 4.9 |
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 83.0 years STANDARD_DEVIATION 3.6 |
| Aortic regurgitation (moderate or severe) | 4 participants |
| Aortic valve area (effective orifice area) | 0.68 cm^2 STANDARD_DEVIATION 0.19 |
| Body mass index | 27.6 kg/m2 STANDARD_DEVIATION 6 |
| Cardiac History Coronary artery disease | 5 participants |
| Cardiac History History of atrial fibrillation | 5 participants |
| Cardiac History Previous coronary artery bypass graft surgery | 0 participants |
| Cardiac History Previous percutaneous coronary intervention | 2 participants |
| Charlson Comorbidity Index Score | 1.8 units on a scale STANDARD_DEVIATION 1.7 |
| EuroScore | 9.5 units on a scale STANDARD_DEVIATION 4.4 |
| General Medical History Chronic obstructive pulmonary disease | 1 participants |
| General Medical History Diabetes mellitus (current) | 5 participants |
| General Medical History Dialysis dependent renal failure | 0 participants |
| General Medical History History of peripheral vascular disease | 1 participants |
| General Medical History Hyperlipidemia (medically treated) | 8 participants |
| General Medical History Hypertension (medically treated) | 10 participants |
| Katz Index | 5.9 units on a scale STANDARD_DEVIATION 0.3 |
| Left Ventricular Ejection Fraction | 62.3 percent of LVEF STANDARD_DEVIATION 7.6 |
| Maximum Grip Strength Average | 15.3 kg STANDARD_DEVIATION 5.7 |
| Mean Aortic Valve Gradient | 53.9 mmHg STANDARD_DEVIATION 20.9 |
| Mini-Cognitive Assessment for Dementia | 3.3 units on a scale STANDARD_DEVIATION 1.5 |
| Mitral Regurgitation (moderate or severe) | 3 participants |
| Modified Rankin Scale 0 | 10 participants |
| Modified Rankin Scale 1 | 0 participants |
| Modified Rankin Scale 2 | 1 participants |
| Modified Rankin Scale 3 or higher | 0 participants |
| Neurological History Cerebrovascular Accident | 2 participants |
| Neurological History Transient Ischemic Attack | 1 participants |
| New York Heart Association Class Class I | 0 participants |
| New York Heart Association Class Class II | 6 participants |
| New York Heart Association Class Class III | 5 participants |
| New York Heart Association Class Class IV | 0 participants |
| Region of Enrollment Australia | 11 participants |
| Serum Albumin | 3.9 g/dL STANDARD_DEVIATION 0.4 |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 0 Participants |
| Society of Thoracic Surgeons (STS) Score | 4.9 units on a scale STANDARD_DEVIATION 2.5 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 6 / 11 |
Outcome results
Primary
Clinical Procedural Success
Clinical procedural success defined as successful implantation of a Lotus Valve System (Device Success) without in-hospital Major Adverse Cardiovascular and Cerebrovascular Events (MACCE) through discharge or 7 days post-procedure, whichever comes first.
Time frame: Discharge or 7 days post-procedure, whichever comes first
Population: Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | Clinical Procedural Success | 9 participants |
Secondary
Central Aortic Regurgitation
As determined by echocardiography
Time frame: Discharge or 7 days post-procedure, whichever comes first
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lotus Valve System | Central Aortic Regurgitation | None | 10 participants |
| Lotus Valve System | Central Aortic Regurgitation | Trivial | 1 participants |
| Lotus Valve System | Central Aortic Regurgitation | Mild | 0 participants |
| Lotus Valve System | Central Aortic Regurgitation | Moderate or Severe | 0 participants |
Secondary
Device Performance Endpoint-Repositioning
Successful repositioning of the Lotus Valve System if repositioning is attempted
Time frame: procedure
Population: Patients in whom repositioning of the Lotus Valve was attempted
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | Device Performance Endpoint-Repositioning | 4 participants |
Secondary
Device Performance Endpoint-Valve Retrieval, if Attempted
Successful retrieval of the Lotus Valve System if retrieval is attempted
Time frame: procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | Device Performance Endpoint-Valve Retrieval, if Attempted | NA participants |
Secondary
Paravalvular Aortic Regurgitation
As determined by echocardiography
Time frame: Discharge or 7 days post-procedure, whichever comes first
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lotus Valve System | Paravalvular Aortic Regurgitation | None | 8 participants |
| Lotus Valve System | Paravalvular Aortic Regurgitation | Trivial | 1 participants |
| Lotus Valve System | Paravalvular Aortic Regurgitation | Mild | 2 participants |
| Lotus Valve System | Paravalvular Aortic Regurgitation | Moderate or Severe | 0 participants |
Other Pre-specified
Acute Kidney Injury - Stage 2 or 3
Stage 2: Increase in serum creatinine to 200-300% (2.0-3.0 times increase compared with baseline). Stage 3: Increase in serum creatinine to ≥ 300% (\> 3 times increase compared with baseline) or serum creatinine of ≥ 4.0 mg/d (≥ 354 μmol/L) with an acute increase of at least 0.5 mg/dl (44 μmol/L). Subjects receiving renal replacement therapy are considered to meet Stage 3 criteria irrespective of other criteria.
Time frame: Discharge or 7 days post-procedure, whichever comes first
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | Acute Kidney Injury - Stage 2 or 3 | 0 participants |
Other Pre-specified
Aortic Valve Area
As determined by echocardiography
Time frame: Discharge or 7 days post-procedure, whichever comes first
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotus Valve System | Aortic Valve Area | 1.53 cm^2 | Standard Deviation 0.18 |
Other Pre-specified
Bleeding
Life-threatening or Disabling Bleeding * Fatal bleeding OR * Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome OR * Bleeding causing hypovolemic shock or severe hypotension requiring vasopressors or surgery OR * Overt source of bleeding with drop in hemoglobin of ≥5 g/dL or whole blood or packed red blood cells (RBC) transfusion ≥4 units Major Bleeding * Overt bleeding either associated with a drop in the hemoglobin level of at least 3.0g/dL or requiring transfusion of 2 or 3 units of whole blood/RBC AND * Does not meet criteria of life-threatening or disabling bleeding
Time frame: Discharge or 7 days post-procedure, whichever comes first
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lotus Valve System | Bleeding | Life-threatening or disabling | 0 participants |
| Lotus Valve System | Bleeding | Major | 2 participants |
Other Pre-specified
Death
Time frame: Discharge or 7 days post-procedure, whichever comes first
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | Death | 0 participants |
Other Pre-specified
Intended Performance of the Lotus Valve
Aortic valve area \>1.0 cm2 plus either a mean aortic valve gradient \<20 mmHg or peak velocity \<3m/sec, without moderate or severe prosthetic valve aortic regurgitation
Time frame: At time of discharge or 7 days post procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | Intended Performance of the Lotus Valve | 10 participants |
Other Pre-specified
Major Stroke
Confirmed with a Modified Rankin score \>/= 2 at 30 and 90 days
Time frame: Discharge or 7 days post-procedure, whichever comes first
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | Major Stroke | 1 participants |
Other Pre-specified
Major Vascular Complication
* Any thoracic aortic dissection * Access site or access-related vascular injury (dissection, stenosis, perforation, rupture, arterio-venous fistula, pseudoaneurysm, hematoma, irreversible nerve injury, or compartment syndrome) leading to either death, need for significant blood transfusions (≥4 units), unplanned percutaneous or surgical intervention, or irreversible end-organ damage (e.g. hypogastric artery occlusion causing visceral ischemia or spinal artery injury causing neurologic impairment) * Distal embolization (non-cerebral) from a vascular source requiring surgery or resulting in amputation or irreversible end-organ damage
Time frame: Discharge or 7 days post-procedure, whichever comes first
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | Major Vascular Complication | 1 participants |
Other Pre-specified
Mean Aortic Valve Gradient
As determined by echocardiography
Time frame: Discharge or 7 days post-procedure, whichever comes first
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotus Valve System | Mean Aortic Valve Gradient | 13.7 mm Hg | Standard Deviation 3.7 |
Other Pre-specified
New Conduction Disturbances or Arrhythmias Requiring Permanent Pacemaker
Time frame: Discharge or 7 days post-procedure, whichever comes first
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | New Conduction Disturbances or Arrhythmias Requiring Permanent Pacemaker | 4 participants |
Other Pre-specified
No Major Adverse Cardiovascular and Cerebrovascular Events Through Discharge
Major adverse cardiovascular or cerebrovascular events include all-cause mortality, periprocedural myocardial infarction ≤72 hours, major stroke, urgent/emergent conversion to surgery or repeat procedure for valve-related dysfunction
Time frame: Discharge or 7 days post-procedure, whichever comes first
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | No Major Adverse Cardiovascular and Cerebrovascular Events Through Discharge | 10 participants |
Other Pre-specified
Peri-procedural Myocardial Infarction
Peri-Procedural Myocardial Infarction (≤72 hours after the index procedure) * New ischemic symptoms (e.g., chest pain or shortness of breath), or new ischemic signs (e.g. ventricular arrhythmias, new or worsening heart failure, new ST-segment changes, hemodynamic instability, or imaging evidence of new loss of viable myocardium or new wall motion abnormality), AND * Elevated cardiac biomarkers (preferably creatine kinase-myoglobin band) within 72 h after the index procedure, consisting of two or more post-procedure samples that are \> 0.6 to 8 h apart with a 20% increase in the second sample and a peak value exceeding 10X the 99th percentile upper reference limit (URL), or a peak value exceeding 5X the 99th percentile URL with new pathological Q waves in at least 2 contiguous leads
Time frame: 72 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | Peri-procedural Myocardial Infarction | 0 participants |
Other Pre-specified
Single Valve Implanted in the Proper Anatomical Location
Time frame: procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | Single Valve Implanted in the Proper Anatomical Location | 11 participants |
Other Pre-specified
Successful Access, Device Delivery, Deployment and Positioning and Retrieval of Delivery System
Time frame: Procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | Successful Access, Device Delivery, Deployment and Positioning and Retrieval of Delivery System | 11 participants |
Other Pre-specified
Urgent/Emergent Conversion to Surgery or Repeat Procedure for Valve-related Dysfunction
Time frame: Discharge or 7 days post-procedure, whichever comes first
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lotus Valve System | Urgent/Emergent Conversion to Surgery or Repeat Procedure for Valve-related Dysfunction | 0 participants |