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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02329496




Registration number
NCT02329496
Ethics application status
Date submitted
19/11/2014
Date registered
31/12/2014
Date last updated
24/05/2018

Titles & IDs
Public title
REPRISE Next Generation Delivery System
Scientific title
REPRISE NGDS: REpositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of LotuS™ ValvE With the Next Generation Delivery System
Secondary ID [1] 0 0
S2332
Universal Trial Number (UTN)
Trial acronym
NGDS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aortic Stenosis 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - Lotus Valve and LOTUS Edge Valve System

Experimental: Lotus Valve and LOTUS Edge Valve System - Transcatheter aortic valve replacement (TAVR) with Lotus Valve System with the Next Generation Delivery System and LOTUS Edge Valve System


Treatment: Devices: Lotus Valve and LOTUS Edge Valve System
Transcatheter aortic valve replacement (TAVR) with the Lotus Valve System with the Next Generation Delivery System and LOTUS Edge Valve System, with either the Lotus Introducer or iSleeve Introducer Sets
Intervention code [1] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Technical Success
Timepoint [1] 0 0
Immediately post-procedure (patient discharged from operative room)
Secondary outcome [1] 0 0
Successful repositioning of the study valve if repositioning is attempted
Timepoint [1] 0 0
Immediately post-procedure (patient discharged from operative room)
Secondary outcome [2] 0 0
Successful retrieval of the study valve if retrieval is attempted
Timepoint [2] 0 0
Immediately post-procedure (patient discharged from operative room)
Secondary outcome [3] 0 0
Severe or moderate paravalvular aortic regurgitation as measured by echocardiography and assessed by an independent core laboratory
Timepoint [3] 0 0
At discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [4] 0 0
Mild, trace/trivial, or no paravalvular aortic regurgitation as measured by echocardiography and assessed by an independent core laboratory
Timepoint [4] 0 0
At discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [5] 0 0
Mean aortic valve pressure gradient as measured by echocardiography and assessed by an independent core laboratory
Timepoint [5] 0 0
At discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [6] 0 0
Effective orifice area as measured by echocardiography and assessed by an independent core laboratory
Timepoint [6] 0 0
At discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [7] 0 0
Peak aortic valve pressure gradient as measured by echocardiography and assessed by an independent core laboratory
Timepoint [7] 0 0
At discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [8] 0 0
Peak aortic velocity as measured by echocardiography and assessed by an independent core laboratory
Timepoint [8] 0 0
At discharge from hospital or at 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [9] 0 0
Mortality: all-cause, cardiovascular, and non-cardiovascular
Timepoint [9] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [10] 0 0
Stroke: disabling and non-disabling
Timepoint [10] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [11] 0 0
Myocardial infarction (MI): periprocedural (=72 hours post index procedure) and spontaneous (>72 hours post index procedure)
Timepoint [11] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [12] 0 0
Bleeding: life-threatening (or disabling) and major
Timepoint [12] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [13] 0 0
Acute kidney injury based on the Acute Kidney Injury Network (AKIN) System Stage 3 (including renal replacement therapy) or Stage 2
Timepoint [13] 0 0
=7 days post index procedure
Secondary outcome [14] 0 0
Major vascular complications major
Timepoint [14] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [15] 0 0
Repeat procedure for valve-related dysfunction (surgical or interventional therapy)
Timepoint [15] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [16] 0 0
Hospitalization for valve-related symptoms or worsening congestive heart failure (NYHA class III or IV)
Timepoint [16] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [17] 0 0
New permanent pacemaker implantation resulting from new or worsened conduction disturbances
Timepoint [17] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [18] 0 0
New onset of atrial fibrillation or atrial flutter
Timepoint [18] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [19] 0 0
Coronary obstruction
Timepoint [19] 0 0
=72 hours post index procedure
Secondary outcome [20] 0 0
Ventricular septal perforation
Timepoint [20] 0 0
=72 hours post index procedure
Secondary outcome [21] 0 0
Mitral apparatus damage
Timepoint [21] 0 0
=72 hours post index procedure
Secondary outcome [22] 0 0
Cardiac tamponade
Timepoint [22] 0 0
=72 hours post index procedure
Secondary outcome [23] 0 0
Prosthetic aortic valve malpositioning, including valve migration, valve embolization, or ectopic valve deployment
Timepoint [23] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [24] 0 0
Transcatheter aortic valve (TAV)-in-TAV deployment
Timepoint [24] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [25] 0 0
Prosthetic aortic valve thrombosis
Timepoint [25] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [26] 0 0
Prosthetic aortic valve endocarditis
Timepoint [26] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [27] 0 0
Neurological status per modified Rankin Scale score
Timepoint [27] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [28] 0 0
Neurological status per National Institutes of Health Stroke Scale
Timepoint [28] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure
Secondary outcome [29] 0 0
Functional Improvement from baseline per NYHA functional classification
Timepoint [29] 0 0
At discharge from hospital or 7 days post-procedure (whichever comes first), 30 days, 6 months, and 12 months post procedure

Eligibility
Key inclusion criteria
1. Subject is =70 years of age

2. Subject has documented calcific native aortic valve stenosis with an initial aortic
valve area (AVA) of =1.0 cm2 (or AVA index of =0.6 cm2/m2) and either a mean pressure
gradient =40 mm Hg or a jet velocity =4 m/s, as measured by echocardiography.

3. Subject has a documented aortic annulus size between =20 and =27.5 mm based on
pre-procedure diagnostic imaging

4. Subject has symptomatic aortic valve stenosis with NYHA Functional Class = II.

5. Subject is considered high risk for surgical valve replacement based on at least one
of the following:

- Society of Thoracic Surgeons (STS) score =8%, and/or

- Agreement by the heart team (which must include an in-person evaluation by an
experienced cardiac surgeon) that subject is at high operative risk of serious
morbidity or mortality with surgical valve replacement.

6. Heart team (which must include an experienced cardiac surgeon) assessment that the
subject is likely to benefit from valve replacement

7. Subject (or legal representative) understands the study requirements and the treatment
procedures, and provides written informed consent.

8. Subject, family member and/or legal representative agree(s) and subject is capable of
returning to the study hospital for all required scheduled follow up visits.
Minimum age
70 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject has a congenital unicuspid or bicuspid aortic valve.

2. Subject 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 creatine kinase-myoglobin band (CK-MB) elevation and/or troponin level
elevation).

3. Subject has had a cerebrovascular accident or transient ischemic attack within the
past 6 months, or has any permanent neurologic defect prior to study enrollment.

4. Subject is on dialysis or has serum creatinine level >3.0 mg/dL or 265 µml/L.

5. Subject has a pre-existing prosthetic heart valve (aortic or mitral) or a prosthetic
ring in any position.

6. Subject has =3+ mitral regurgitation, =3+ aortic regurgitation or =3+ tricuspid
regurgitation (i.e., subject cannot have more than moderate mitral, aortic or
tricuspid regurgitation).

7. Subject has a need for emergency surgery for any reason.

8. Subject has a history of endocarditis within 12 months of index procedure or evidence
of an active systemic infection or sepsis.

9. Subject has echocardiographic evidence of intra-cardiac mass, thrombus or vegetation.

10. Subject has Hgb <9 g/dL, platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or
white blood cell count <1,000 cells/mm3.

11. Subject is receiving chronic (=72 hours) anticoagulation therapy (warfarin), and
cannot tolerate concomitant therapy with aspirin or clopidogrel (subjects who require
chronic anticoagulation must additionally be able to be treated with either aspirin or
clopidogrel).*

12. Subject has active peptic ulcer disease or gastrointestinal bleed within the past 3
months, other bleeding diathesis or coagulopathy or will refuse transfusions.

13. Subject 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.

14. Subject 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.

15. Subject has hypertrophic obstructive cardiomyopathy.

16. Subject has any therapeutic invasive cardiac procedure within 30 days prior to the
index procedure (except for balloon aortic valvuloplasty and pacemaker implantation
which are allowed).

17. Subject has untreated coronary artery disease, which in the opinion of the treating
physician, is clinically significant and requires revascularization.

18. Subject has documented left ventricular ejection fraction <30%.

19. Subject is in cardiogenic shock or has hemodynamic instability requiring inotropic
support or mechanical support devices.

20. Subject has severe peripheral vascular disease (including aneurysm defined as maximal
luminal diameter >5 cm or with documented presence of thrombus, marked tortuosity,
narrowing of the abdominal aorta, severe unfolding of the thoracic aorta or thick [>5
mm] protruding or ulcerated atheroma in the aortic arch) or symptomatic carotid or
vertebral disease.

21. Femoral artery lumen of <6.0 mm for subjects requiring 23 mm valve size or <6.5 mm for
subjects requiring 27 mm valve size, or severe iliofemoral tortuosity or calcification
that would prevent safe placement of the introducer sheath.

22. Current problems with substance abuse (e.g., alcohol, etc.).

23. Subject is participating in another investigational drug or device study that has not
reached its primary endpoint.

24. Subject has untreated conduction system disorder (e.g., Type II second degree
atrioventricular block) that in the opinion of the treating physician is clinically
significant and requires a pacemaker implantation.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/12/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/10/2017
Sample size
Target
Accrual to date
Final
38
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Prince Charles Hospital - Chermside
Recruitment hospital [2] 0 0
Monash Heart - Clayton
Recruitment postcode(s) [1] 0 0
4032 - Chermside
Recruitment postcode(s) [2] 0 0
3168 - Clayton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Boston Scientific Corporation
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To confirm the acute performance and safety of the Lotus™ Valve with the Next Generation
Delivery System for transcatheter aortic valve replacement (TAVR) in symptomatic patients
with severe calcific aortic stenosis who are considered high risk for surgical valve
replacement.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02329496
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Robert Gooley, MD
Address 0 0
Monash
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries