REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve SystEm (REPRISE I)

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.

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis; Aortic Valve Disease; Aortic Valve Calcification
• Intervention / Treatment: Device: Lotus Valve System

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3040
      • St. Vincent's Hospital
    • Melbourne, Victoria, Australia, 3168
      • Southern Health Monash Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lotus Valve System; Patients enrolled in the study to receive treatment with the Lotus Valve System for symptomatic aortic valve stenosis	Device: Lotus 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Discharge or 7 days post-procedure, whichever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Performance Endpoint-Repositioning	Successful repositioning of the Lotus Valve System if repositioning is attempted	procedure
Device Performance Endpoint-Valve Retrieval, if Attempted	Successful retrieval of the Lotus Valve System if retrieval is attempted	procedure
Central Aortic Regurgitation	As determined by echocardiography	Discharge or 7 days post-procedure, whichever comes first
Paravalvular Aortic Regurgitation	As determined by echocardiography	Discharge or 7 days post-procedure, whichever comes first

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful Access, Device Delivery, Deployment and Positioning and Retrieval of Delivery System		Procedure
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	At time of discharge or 7 days post procedure
Single Valve Implanted in the Proper Anatomical Location		procedure
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	Discharge or 7 days post-procedure, whichever comes first
Mean Aortic Valve Gradient	As determined by echocardiography	Discharge or 7 days post-procedure, whichever comes first
Aortic Valve Area	As determined by echocardiography	Discharge or 7 days post-procedure, whichever comes first
Death		Discharge or 7 days post-procedure, whichever comes first
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	72 hours
Major Stroke	Confirmed with a Modified Rankin score >/= 2 at 30 and 90 days	Discharge or 7 days post-procedure, whichever comes first
Urgent/Emergent Conversion to Surgery or Repeat Procedure for Valve-related Dysfunction		Discharge or 7 days post-procedure, whichever comes first
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	Discharge or 7 days post-procedure, whichever comes first
New Conduction Disturbances or Arrhythmias Requiring Permanent Pacemaker		Discharge or 7 days post-procedure, whichever comes first
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	Discharge or 7 days post-procedure, whichever comes first
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.	Discharge or 7 days post-procedure, whichever comes first

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Principal Investigator: Ian Meredith, MBBS, PhD, Southern Health, Monash Medical Centre

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 9, 2017

Study Registration Dates

• First Submitted: June 27, 2011
• First Submitted That Met QC Criteria: June 27, 2011
• First Posted (Estimate): June 28, 2011

Study Record Updates

• Last Update Posted (Actual): June 20, 2017
• Last Update Submitted That Met QC Criteria: May 23, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Aortic Valve Stenosis; Transcatheter Aortic Valve Replacement
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Aortic Valve Disease
• Other Study ID Numbers: TP3659

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no plan to make individual participant data (IPD) available.