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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boston Scientific Corporation
ClinicalTrials.gov Identifier:
NCT01383720
First received: June 27, 2011
Last updated: May 1, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention
Aortic Valve Stenosis
Aortic Valve Calcification
Aortic Valve Disease
Device: Lotus Valve System

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus™ Valve SystEm

Resource links provided by NLM:


Further study details as provided by Boston Scientific Corporation:

Primary Outcome Measures:
  • Clinical Procedural Success [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • Device Performance Endpoint-Repositioning [ Time Frame: procedure ] [ Designated as safety issue: No ]
    Successful repositioning of the Lotus Valve System if repositioning is attempted

  • Device Performance Endpoint-Valve Retrieval, if Attempted [ Time Frame: procedure ] [ Designated as safety issue: No ]
    Successful retrieval of the Lotus Valve System if retrieval is attempted

  • Central Aortic Regurgitation [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: Yes ]
    As determined by echocardiography

  • Paravalvular Aortic Regurgitation [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: Yes ]
    As determined by echocardiography


Other Outcome Measures:
  • Successful Access, Device Delivery, Deployment and Positioning and Retrieval of Delivery System [ Time Frame: Procedure ] [ Designated as safety issue: No ]
  • Intended Performance of the Lotus Valve [ Time Frame: At time of discharge or 7 days post procedure ] [ Designated as safety issue: No ]
    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 [ Time Frame: procedure ] [ Designated as safety issue: No ]
  • No Major Adverse Cardiovascular and Cerebrovascular Events Through Discharge [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: No ]
    As determined by echocardiography

  • Aortic Valve Area [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: No ]
    As determined by echocardiography

  • Death [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: Yes ]
  • Peri-procedural Myocardial Infarction [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: Yes ]
    Confirmed with a Modified Rankin score >/= 2 at 30 and 90 days

  • Urgent/Emergent Conversion to Surgery or Repeat Procedure for Valve-related Dysfunction [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: No ]
  • Major Vascular Complication [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: No ]
    • 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 [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: No ]
  • Bleeding [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: No ]

    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 [ Time Frame: Discharge or 7 days post-procedure, whichever comes first ] [ Designated as safety issue: No ]

    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.



Enrollment: 11
Study Start Date: April 2012
Estimated Study Completion Date: May 2017
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   70 Years and older   (Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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 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 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 within 30 days of the index procedure (defined as Q wave MI, or non-Q wave MI with total 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 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 AV block, bifascicular or trifascicular block.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01383720

Locations
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
St. Vincent's Hospital
Melbourne, Victoria, Australia, 3040
Southern Health Monash Medical Centre
Melbourne, Victoria, Australia, 3168
Sponsors and Collaborators
Boston Scientific Corporation
Investigators
Principal Investigator: Ian Meredith, MBBS, PhD Southern Health, Monash Medical Centre
  More Information

Responsible Party: Boston Scientific Corporation
ClinicalTrials.gov Identifier: NCT01383720     History of Changes
Other Study ID Numbers: TP3659 
Study First Received: June 27, 2011
Results First Received: April 16, 2013
Last Updated: May 1, 2016
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Individual Participant Data  
Plan to Share IPD: No
Plan Description: There is no plan to make individual participant data (IPD) available.

Keywords provided by Boston Scientific Corporation:
Aortic Valve Stenosis
Transcatheter Aortic Valve Replacement

Additional relevant MeSH terms:
Calcinosis
Aortic Valve Stenosis
Calcium Metabolism Disorders
Metabolic Diseases
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction

ClinicalTrials.gov processed this record on December 02, 2016