Clinical trial NCT01876420: The Medtronic CoreValve™ Evolut R™ CE Mark Clinical Study
Official title: The Medtronic CoreValve™ Evolut R™ CE Mark Clinical Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aortic Stenosis
Lead sponsor: Medtronic Cardiovascular
Sponsor class: INDUSTRY
Collaborators: name: Medtronic
First posted: 2013-06-12
Enrollment: 60
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the safety and clinical performance of the CoreValve™ Evolut R™ System.

Detailed description: The study objectives are to assess the safety and clinical performance of the CoreValve™ Evolut R™ System in patients with severe symptomatic aortic stenosis who are considered at high through extreme risk for surgical aortic valve replacement. These objectives will be accomplished by a prospective clinical study involving up to 60 implanted subjects among up to six study centers.

Eligibility criteria: Inclusion Criteria:

1. Severe aortic stenosis, defined as aortic valve area of \< 1.0 cm2 (or aortic valve area index of \< 0.6 cm2/m2) by the continuity equation, AND mean gradient \> 40 mmHg or maximal aortic valve velocity \> 4.0 m/sec by resting echocardiogram.
2. Estimated 30 day mortality risk of \> 15% by study center Heart Team assessment,33 OR at least two cardiovascular surgeons from the study center deny surgery because of prohibitive operative risk, estimated to be a combined \>50% risk of irreversible mortality or morbidity.
3. Symptoms of aortic stenosis, and NYHA Functional Class II or greater.
4. The subject meets the legal minimum age to provide informed consent based on local regulatory requirements, and has provided written informed consent as approved by the EC/IRB of the respective clinical site.
5. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.

   Exclusion Criteria:

   Clinical exclusion criteria:
6. Subject has been offered SAVR but has declined.
7. Any condition considered a contraindication for placement of a bioprosthetic valve (e.g. subject is indicated for mechanical prosthetic valve).
8. Known hypersensitivity or contraindication to Nitinol.
9. Blood dyscrasias as defined: leukopenia (WBC \<1000 mm3), thrombocytopenia (platelet count \<50,000 cells/mm3), history of bleeding diathesis or coagulopathy, or hypercoagulable states.
10. Untreated clinically significant coronary artery disease requiring revascularization.
11. Severe left ventricular dysfunction with left ventricular ejection fraction (LVEF) \<20% by echocardiography, contrast ventriculography, or radionuclide ventriculography.
12. End stage renal disease requiring chronic dialysis of creatinine clearance \< 20 cc/min.
13. Ongoing sepsis, including active endocarditis.
14. Any condition considered a contraindication to extracorporeal assistance.
15. Any percutaneous coronary or peripheral interventional procedure with a bare metal stent performed within 30 days prior to Heart Team assessment, or within six months prior to Heart Team assessment for procedures with a drug eluting stents.
16. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within eight weeks of Heart Team Assessment .
17. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.
18. Recent (within 6 months of Heart Team assessment) cerebrovascular accident (CVA) or transient ischemic attack (TIA).
19. Gastrointestinal (GI) bleeding that would preclude anticoagulation.
20. Subject refuses a blood transfusion.
21. Severe dementia (resulting in either inability to provide informed consent for the study/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).
22. Estimated life expectancy of less than 12 months due to associated non-cardiac co-morbid conditions.
23. Other medical, social, or psychological conditions that in the opinion of the Investigator precludes the subject from appropriate consent or adherence to the protocol required follow-ups exams.
24. Currently participating in an investigational drug or another device study (excluding registries).
25. Evidence of an acute myocardial infarction ≤30 days before the index procedure.
26. Need for emergency surgery for any reason.
27. Liver failure (Child-C).
28. Subject is pregnant or breast feeding.

    Anatomical exclusion criteria:
29. Pre-existing prosthetic heart valve in any position.
30. Mixed aortic valve disease (aortic stenosis with moderate or severe aortic regurgitation).
31. Severe mitral regurgitation.
32. Severe tricuspid regurgitation.
33. Moderate or severe mitral stenosis.
34. Hypertrophic obstructive cardiomyopathy.
35. Echocardiographic or Multi-Slice Computed Tomography (MSCT) evidence of intracardiac mass thrombus or vegetation.
36. Congenital bicuspid or unicuspid valve verified by echocardiography.

Primary outcomes:
measure: All-cause Mortality Rate at 30 Days
timeFrame: 30 days
measure: Stroke Rate (Disabling and Non-disabling) at 30 Days
timeFrame: 30 days
measure: Device Success Rate at 24 Hours to Seven Days
timeFrame: 24 hours to seven days
Secondary outcomes:
measure: VARC II Combined Safety Endpoint at 30 Days
timeFrame: 30 days
measure: Event Rates of the Individual Components of the VARC II Composite Safety Endpoint at 30 Days
timeFrame: 30 days
measure: Hemodynamic Performance Metrics at 30 Days by Doppler Echocardiography - Mean Gradient
timeFrame: 30 days
measure: Hemodynamic Performance Metrics at 30 Days by Doppler Echocardiography - • Effective Orifice Area (EOA)
timeFrame: 30 days
measure: Hemodynamic Performance Metrics at 30 Days by Doppler Echocardiography - Total Aortic Regurgitation (Transvalvular & Paravalvular)
timeFrame: 30 days
measure: Resheath or Recapture Success Rate (When Attempted), Where Successful Recapture is Defined as Evolut R™ TAV (Including the Frame) is Fully Resheathed Into the Capsule of the Delivery Catheter, as Verified by Fluoroscopy.
timeFrame: Day 1
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Epworth Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Monash Medical Center
state: Victoria
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Belfast
country: United Kingdom
facility: Royal Victoria Hospital
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: St. George's Hospital
Study officials:
affiliation: Director Clinical Research Structural Heart
name: Eric Vang, PhD
role: STUDY_DIRECTOR
References:
citation: Manoharan G, Walton AS, Brecker SJ, Pasupati S, Blackman DJ, Qiao H, Meredith IT. Treatment of Symptomatic Severe Aortic Stenosis With a Novel Resheathable Supra-Annular Self-Expanding Transcatheter Aortic Valve System. JACC Cardiovasc Interv. 2015 Aug 24;8(10):1359-1367. doi: 10.1016/j.jcin.2015.05.015.