ACURATE Prime XL Human Feasibility Study

Aortic Stenosis Clinical Trial

Official title:

A Study to Evaluate the Feasibility and Safety of the ACURATE Prime™ XL Aortic Valve System in Patients Indicated for TAVI: ACURATE Prime XL Human Feasibility Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05224245
• Other study ID #: S2458
• Status: Completed
• Phase: N/A
• Start date: March 3, 2022
• Est. completion date: May 24, 2023

Study information

• Verified date: June 2023
• Source: Boston Scientific Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate feasibility and safety of the ACURATE Prime™ XL Transfemoral Aortic Valve System for transcatheter aortic valve implantation (TAVI) in subjects with severe native aortic stenosis who are indicated for TAVI.

Description:

The ACURATE Prime XL Human Feasibility Study (ACURATE Prime XL HFS) is a prospective, multicenter, open-label, single-arm study designed to evaluate feasibility and safety of the ACURATE Prime XL Transfemoral Aortic Valve System for TAVI in subjects who have severe native aortic stenosis and are indicated for TAVI. Subjects who provide written informed consent, meet all eligibility criteria, and are approved by the Case Review Committee (CRC) are considered enrolled when an attempt is made to insert the iSLEEVE Introducer into the subject's femoral artery. There will be up to 20 subjects enrolled at up to 6 centers in Australia and Europe. All subjects implanted with a study valve will be assessed at baseline, peri- and post-procedure, at discharge or 7 days post index procedure (whichever comes first), 30 days, 6 months, and 1 year. Subjects who are enrolled but not implanted with a study valve at the time of the procedure will be followed for safety through 30 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: May 24, 2023
• Est. primary completion date: June 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• IC1. Subject has documented severe symptomatic native aortic stenosis defined as follows: aortic valve area (AVA) =1.0 cm2 (or AVA index =0.6 cm2/m2) AND a mean pressure gradient =40 mmHg, OR maximal aortic valve velocity =4.0 m/s, OR Doppler velocity index =0.25 as measured by echocardiography and/or invasive hemodynamics. Note: In cases of low flow, low gradient aortic stenosis with left ventricular dysfunction (ejection fraction <50%), dobutamine can be used to assess the grade of aortic stenosis (maximum dobutamine dose of 20 mcg/kg/min recommended); the subject may be included in the study if echocardiographic criteria are met with this augmentation.
• IC2. Subject has a documented aortic annulus diameter of =26.5 mm and =29 mm based on the center's assessment of pre-procedure diagnostic imaging (and confirmed by the Case Review Committee [CRC]).
• IC3. For subjects with symptomatic aortic valve stenosis per IC1 definition above, functional status is NYHA Functional Class = II.
• IC4. Heart team (composition per local standards, but at a minimum must include an experienced cardiac surgeon) agrees that the subject is indicated for TAVI, is likely to benefit from prosthetic valve implantation, and TAVI is appropriate.
• IC5. Subject (or legal representative) understands the study requirements and the treatment procedures and provides written informed consent.
• IC6. 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.
• IC7. Subject is expected to be able to take the protocol-required adjunctive pharmacologic therapy.

Exclusion Criteria:

• EC1. Subject has a unicuspid or bicuspid aortic valve.
• EC2. Subject has had an acute myocardial infarction within 30 days prior to 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 elevation).
• EC3.Subject has had a cerebrovascular accident or transient ischemic attack clinically confirmed by a neurologist or neuroimaging within the past 6 months prior to study enrollment.
• EC4.Subject has eGFR < 20 mL/min (based on hospital preferred method) but is not on renal replacement therapy.
• EC5. Subject has a pre-existing prosthetic aortic or mitral valve.
• EC6. Subject has severe (4+) aortic, tricuspid, or mitral regurgitation.
• EC7. Subject has moderate or severe mitral stenosis (mitral valve area =1.5 cm2 and diastolic pressure half-time =150 ms, Stage C or D).
• EC8. Subject has a need for emergency surgery for any reason.
• EC9. Subject has a history of endocarditis within 6 months of index procedure or evidence of an active systemic infection or sepsis.
• EC10. Subject has echocardiographic evidence of new intra-cardiac vegetation or intraventricular or paravalvular thrombus requiring intervention.
• EC11. Subject has platelet count <50,000 cells/mm3 or >700,000 cells/mm3, or white blood cell count <1,000 cells/mm3.
• EC12. Subject has had a gastrointestinal bleed requiring hospitalization or transfusion within the past 3 months or has other clinically significant bleeding diathesis or coagulopathy that would preclude treatment with required antiplatelet regimen or will refuse transfusions.
• EC13. Subject has known hypersensitivity to the following:
• Contrast agents that cannot be adequately pre-medicated, OR
• Protocol-required medications (aspirin, all P2Y12 inhibitors, heparin), OR
• Individual components of the investigational valve and/or delivery system (stainless steel, platinum, iridium, nickel, titanium, or polyethylene terephthalate [PET]).
• EC14. Subject has a life expectancy of less than 12 months due to non-cardiac, comorbid conditions based on the assessment of the investigator at the time of enrollment.
• EC15. Subject has hypertrophic cardiomyopathy.
• EC16. Subject has any therapeutic invasive cardiac or vascular procedure within 30 days prior to the index procedure (except for balloon aortic valvuloplasty, pacemaker implantation, or implantable cardioverter defibrillator implantation, which are allowed).
• EC17. Subject has untreated coronary artery disease, which in the opinion of the treating physician is clinically significant and requires revascularization.
• EC18. Subject has severe left ventricular dysfunction with ejection fraction <20%.
• EC19. Subject is in cardiogenic shock or has hemodynamic instability requiring inotropic support or mechanical support devices.
• EC20. Subject has arterial access that is not acceptable for the study device delivery system as defined in the Instructions For Use.
• EC21. Subject has either of the following:
• Severe vascular disease that would preclude safe access (e.g., aneurysm with thrombus that cannot be crossed safely; marked tortuosity; significant narrowing of the abdominal aorta; severe unfolding of the thoracic aorta; or thick, protruding, ulcerated atheroma in the aortic arch), OR
• Severe/eccentric calcification of the aortic annulus that would prevent safe implantation of the TAVI prosthesis.
• EC22. Subject has current problems with substance abuse (e.g., alcohol, etc.) that may interfere with the subject's participation in this study.
• EC23. Subject is participating in another investigational drug or device study that has not reached its primary endpoint or subject intends to participate in another investigational device clinical trial within 12 months after the index procedure.
• EC24. 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. Enrollment is permissible after permanent pacemaker implantation.
• EC25. Subject has severe incapacitating dementia.

Related Conditions & MeSH terms

• Aortic Stenosis
• Aortic Valve Stenosis

Intervention

Device:
• ACURATE Prime XL Transfemoral Aortic Valve System
ACURATE Prime™ Transfemoral Aortic Valve system: Support frame made of nitinol, supra-annular processed tri-leaflet porcine pericardial valve and an outer skirt to limit paravalvular regurgitation (manufactured by Boston Scientific Corporation, Marlborough, MA, USA).

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Brisbane	Queensland
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Health	Clayton	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Boston Scientific Corporation

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants who died including all-cause, cardiovascular, and non-cardiovascular death	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants who experienced a Stroke including disabling and non-disabling	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with Myocardial infarction (MI): periprocedural (=72 hours post index procedure) and spontaneous (>72 hours post index procedure)	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with Bleeding: life-threatening (or disabling) and major	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with Acute kidney injury based on the AKIN System Stage 3 (including renal replacement therapy) or Stage 2	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	=7 days post index procedure
Other	Number of participants with Major vascular complication	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with Repeat procedure for valve-related dysfunction (surgical or interventional therapy)	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with Hospitalization for valve-related symptoms or worsening congestive heart failure (New York Heart Association [NYHA] class III or IV)	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with New permanent pacemaker implantation (PPI) resulting from new or worsened conduction disturbances	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with New onset of atrial fibrillation or atrial flutter	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with Coronary obstruction: periprocedural	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	=72 hours post index procedure
Other	Number of participants with Ventricular septal perforation: periprocedural	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	=72 hours post index procedure
Other	Number of participants with Mitral apparatus damage: periprocedural	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	=72 hours post index procedure
Other	Number of participants with Cardiac tamponade: periprocedural	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	=72 hours post index procedure
Other	Number of participants with Valve migration	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with Valve embolization	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with Ectopic valve deployment	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with Transcatheter aortic valve (TAV)-in-TAV deployment	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with Prosthetic aortic valve thrombosis	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with Prosthetic aortic valve endocarditis	Adjudicated by an independent Clinical Events Committee (CEC) based on VARC 2 definitions	Participants will be followed for the duration of hospital stay, through 30 days, 6 months, and 1 year
Other	Number of participants with successful vascular access, delivery and deployment of the study valve, and successful retrieval of the delivery system (site reported assessment)	Device Performance endpoint, as measured by site reported data	Participants will be followed for the duration of their procedure, an expected average of 1 day (peri- and post-procedure)
Other	Grade of aortic regurgitation/paravalvular leak (PVL) (echocardiographic assessment)	Device Performance endpoint, as assessed by Echocardiographic Core Laboratory	Participants will be followed for the duration of their procedure, an expected average of 1 day (peri- and post-procedure)
Other	Prosthetic aortic valve performance: Effective Orifice Area (EOA)	Effective Orifice Area (EOA), as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory	Discharge or 7 days post index procedure (whichever comes first), 30 days, 6 months, and 1 year
Other	Prosthetic aortic valve performance: Mean Aortic Gradient	Mean aortic gradient as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory	Discharge or 7 days post index procedure (whichever comes first), 30 days, 6 months, and 1 year
Other	Prosthetic aortic valve performance: Peak Aortic Gradient	Peak Aortic Gradient as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory	Discharge or 7 days post index procedure (whichever comes first), 30 days, 6 months, and 1 year
Other	Prosthetic aortic valve performance: Peak Aortic Velocity	Peak Aortic Velocity as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory	Discharge or 7 days post index procedure (whichever comes first), 30 days, 6 months, and 1 year
Other	Prosthetic aortic valve performance: Grade of Aortic Regurgitation/PVL	Grade of Aortic Regurgitation/PVL as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory	Discharge or 7 days post index procedure (whichever comes first), 30 days, 6 months, and 1 year
Other	Number of participants with a New York Heart Association (NYHA) Functional Status classification of Class I, II, III or IV	Evaluated by New York Heart Association (NYHA) classification	Discharge or 7 days post index procedure (whichever comes first), 30 days, 6 months, and 1 year
Other	Neurological status: Participant score for National Institutes of Health Stroke Scale (NIHSS) assessment	Evaluated by National Institutes of Health Stroke Scale (NIHSS) - Minimum: 0 (No stroke symptoms); Max: 21-42 (Severe stroke)	Discharge or 7 days post index procedure (whichever comes first) and 1 year and when is stroke is suspected
Other	Neurological status: Participant score for Modified Rankin Scale (mRS) Assessment	Evaluated by Modified Rankin Scale (mRS) - min: 0 (The patient has no residual symptoms); max: 6 (The patient has expired)	Discharge or 7 days post index procedure (whichever comes first), 30 days, 6 months, and 1 year, and when is stroke is suspected (and 90 days post stroke)
Other	Neurological status: Number of participants with a confirmed stroke per Neurological physical exam assessment	Evaluated per neurological physical exam in all subjects where stroke is suspected	Participants will be followed for the duration of the trial, through 1 year
Primary	Number of participants with Device Success	Absence of procedural mortality, AND Correct positioning of a single valve into the proper anatomical location, AND Intended performance of the study device (indexed effective orifice area [iEOA] >0.85 cm2/m2 for BMI <30 kg/m2 and iEOA >0.70 cm2/m2 for BMI =30 kg/m2 plus either a mean aortic valve gradient <20 mmHg or a peak velocity <3m/sec, and no moderate or severe prosthetic valve aortic regurgitation) as measured by transthoracic echocardiography (TTE) and assessed by an independent core laboratory.	Through discharge or 7 days post procedure
Primary	Number of participants who died or experienced a stroke	Composite of all-cause mortality and all stroke; A Clinical Events Committee (CEC), independent group of physician experts will be used to evaluate all reported cases of death and stroke to determine whether they met the specific protocol definition of the event.	Through 30 Days post procedure