Portico and Navitor India Clinical Trial

Study Overview
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Brief Summary
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The objective of this clinical trial is to collect data on procedural safety and device performance of the Portico and Navitor devices and FlexNav delivery system to treat patients with severe aortic stenosis in the Indian population.

Detailed Description
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The objective of this Phase IV clinical trial is to characterize the procedural safety and device performance of the Portico valve, the Navitor Valve, the FlexNav delivery system and FlexNav or Navitor loading system to treat patients with severe aortic stenosis.

Official Title
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Portico and Navitor India Clinical Trial

Conditions
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Aortic Valve Stenosis, Aortic Valve Failure, Aortic Insufficiency, Aortic Stenosis

Intervention / Treatment
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* Device: Transcatheter Aortic Valve Replacement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must provide written informed consent prior to any clinical investigation-related procedure. Are >60 years of age in host country, have severe symptomatic (NYHA class ≥ II) aortic stenosis (AS), at high or extreme surgical risk and have been identified as a candidate for a Portico or Navitor valve implant. Subjects must have a Society of Thoracic Surgeons (STS) score of ≥7% OR documented heart team agreement of high or extreme risk for surgical aortic valve replacement due to frailty or co-morbidities not captured by the STS score. Exclusion Criteria: Have tested positive for the Corona Virus Disease 2019 (COVID-19) virus at any time AND currently have residual signs or symptoms associated with the COVID-19 virus (eg. evidence of thrombosis, damaged/inflamed heart muscle, damaged/inflamed lung tissue, etc.) Have sepsis, including active endocarditis Have any evidence of left ventricular or atrial thrombus Have vascular conditions (i.e. caliber, stenosis, tortuosity, or severe calcification) that make insertion and endovascular access to the aortic valve improbable Have a non-calcified aortic annulus Have congenital bicuspid or unicuspid leaflet configuration Are unable to tolerate antiplatelet/anticoagulant therapy Are pregnant at the time of signing informed consent Are currently participating in a drug or device study that may impact this study (unless prior sponsor approval for co-enrollment is granted)

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Analysis Population<br>The analysis population will include patients considered at high or extreme surgical risk, who have met all inclusion criteria, have not met any exclusion criteria, have signed an Ethics Committee (EC) approved Informed Consent, and, at the minimum, the FlexNav delivery system entered his/her vasculature for an attempted Portico or Navitor Valve implant | Device: Transcatheter Aortic Valve Replacement<br>* Transcatheter Aortic Valve Replacement for the treatment of patients with severe aortic stenosis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VARC-2 and VARC-3 defined event rate of All cause mortality rate (percent of subjects) at 30 days from the implant/index procedure | The outcome measures will be defined for all VARC-2 and VARC-3 defined endpoints per the published VARC-2 and VARC-3 definitions: Kappetein et al. J Thorac Cardiovasc Surg: 2013;145:6-23. Genereux et al. European Heart Journal: 2021; 00, 1-33 | 30 days post index procedure | 
| VARC-2 and VARC-3 defined event rate of Cardiovascular mortality rate (percent of subjects) at 30 days from the implant/index procedure | The outcome measures will be defined for all VARC-2 and VARC-3 defined endpoints per the published VARC-2 and VARC-3 definitions: Kappetein et al. J Thorac Cardiovasc Surg: 2013;145:6-23. Genereux et al. European Heart Journal: 2021; 00, 1-33. | 30 days post index procedure | 
| VARC-2 and VARC-3 defined event rate of Myocardial Infarction rate (percent of subjects) at 30 days from the implant/index procedure | The outcome measures will be defined for all VARC-2 and VARC-3 defined endpoints per the published VARC-2 and VARC-3 definitions: Kappetein et al. J Thorac Cardiovasc Surg: 2013;145:6-23. Genereux et al. European Heart Journal: 2021; 00, 1-33. | 30 days post index procedure | 
| VARC-2 and VARC-3 defined event rate of Stroke (including disabling and non-disabling, percent of subjects) at 30 days from the implant/index procedure | The outcome measures will be defined for all VARC-2 and VARC-3 defined endpoints per the published VARC-2 and VARC-3 definitions: Kappetein et al. J Thorac Cardiovasc Surg: 2013;145:6-23. Genereux et al. European Heart Journal: 2021; 00, 1-33. | 30 days post index procedure | 
| VARC-2 and VARC-3 defined event rate of Bleeding (life-threatening, major, minor, percent of subjects) at 30 days from the implant/index procedure | The outcome measures will be defined for all VARC-2 and VARC-3 defined endpoints per the published VARC-2 and VARC-3 definitions: Kappetein et al. J Thorac Cardiovasc Surg: 2013;145:6-23. Genereux et al. European Heart Journal: 2021; 00, 1-33. | 30 days post index procedure | 
| VARC-2 and VARC-3 defined event rate of Acute kidney injury (percent of subjects) at 30 days from the implant/index procedure | The outcome measures will be defined for all VARC-2 and VARC-3 defined endpoints per the published VARC-2 and VARC-3 definitions: Kappetein et al. J Thorac Cardiovasc Surg: 2013;145:6-23. Genereux et al. European Heart Journal: 2021; 00, 1-33. | 30 days post index procedure | 
| VARC-2 and VARC-3 defined event rate of Vascular access site and access-related complications (major and minor, percent of subjects) at 30 days from the implant/index procedure | The outcome measures will be defined for all VARC-2 and VARC-3 defined endpoints per the published VARC-2 and VARC-3 definitions: Kappetein et al. J Thorac Cardiovasc Surg: 2013;145:6-23. Genereux et al. European Heart Journal: 2021; 00, 1-33. | 30 days post index procedure | 
| VARC-2 and VARC-3 defined event rate of Coronary obstruction (percent of subjects) at 30 days from the implant/index procedure | The outcome measures will be defined for all VARC-2 and VARC-3 defined endpoints per the published VARC-2 and VARC-3 definitions: Kappetein et al. J Thorac Cardiovasc Surg: 2013;145:6-23. Genereux et al. European Heart Journal: 2021; 00, 1-33. | 30 days post index procedure | 
| VARC-2 and VARC-3 defined event rate of Permanent pacemaker insertion (percent of subjects) at 30 days from the implant/index procedure | The outcome measures will be defined for all VARC-2 and VARC-3 defined endpoints per the published VARC-2 and VARC-3 definitions: Kappetein et al. J Thorac Cardiovasc Surg: 2013;145:6-23. Genereux et al. European Heart Journal: 2021; 00, 1-33. | 30 days post index procedure | 
| Access Vessel Diameter (mm) during procedure | The access vessel diameter (mm) will be analyzed at index/implant procedure to define delivery profile characteristics | During procedure | 
| Sheath Utilization during procedure | The Sheath Utilization will be analyzed at index/implant procedure to define delivery profile characteristics (unit = percent using sheath) | During procedure | 
| Sheath Size during procedure | The Sheath Size will be analyzed at index/implant procedure to define delivery profile characteristics (unit = French (F)) | During procedure | 
| Percentage of Subjects with Implant Success | Defined as absence of procedural mortality, correct positioning of a single Portico prosthetic heart valve into the proper anatomical location, no conversion to open surgery | During procedure | 
| Echocardiographic assessment of the mean gradient at 30 days compared to baseline for the subjects with Portico valve implanted | Units=mmHg | 30 days post index procedure | 
| Echocardiographic assessment of Effective Orifice Area (EOA) at 30 days compared to baseline for the subjects with Portico valve | units = cm2 | 30 days post index procedure | 
| Echocardiographic assessment of Paravalvular Leak (PVL) per VARC-2 definitions at 30 days compared to baseline for the subjects with Portico valve implanted | Reported as either none/trace, mild, moderate, or severe | 30 days post index procedure | 
| VARC-2 and VARC-3 defined event rate of All-Cause Mortality (percent of subjects) beyond 30 days through 9 from the implant/index procedure | The outcome measures will be defined for all VARC-2 and VARC-3 defined endpoints per the published VARC-2 and VARC-3 definitions: Kappetein et al. J Thorac Cardiovasc Surg: 2013;145:6-23. Genereux et al. European Heart Journal: 2021; 00, 1-33. | 9 months post index procedure | 
| VARC-2 and VARC-3 defined event rate of Stroke (including disabling and non-disabling, percent of subjects) beyond 30 days through 9 from the implant/index procedure | The outcome measures will be defined for all VARC-2 and VARC-3 defined endpoints per the published VARC-2 and VARC-3 definitions: Kappetein et al. J Thorac Cardiovasc Surg: 2013;145:6-23. Genereux et al. European Heart Journal: 2021; 00, 1-33. | 9 months post index procedure | 
| Clinical improvement from baseline to 30 days and baseline to 9-months for the subjects with Portico valve implanted assessed by New York Heart Association (NYHA) functional class | Reported as the percent of subjects with improvement, worsening, or stable NYHA class from baseline to 30 days and from baseline to 9 months; NYHA Class will be measured as class I, II, III, or IV, symptoms are worsening from I to IV. | 30 days post index procedure | 
| Clinical improvement from baseline to 30 days and baseline to 9-months for the subjects with Portico valve implanted assessed by Quality of Life (QoL) questionnaire (5-level EQ-5D version (EQ5D-5L)) | Reported as the percent of subjects with improvement, worsening, or stable from baseline to 30 days and from baseline to 9 months | 9 months post index procedure |