The Medtronic Harmony™ Transcatheter Pulmonary Valve Clinical Study

Study Overview
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Brief Summary
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The purpose of this study is to further evaluate the safety and effectiveness of the Harmony™ TPV system.

Detailed Description
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The continued clinical experience addendum is a prospective, multi-center, non-randomized, interventional study to evaluate the safety and effectiveness of the Harmony TPV system. All implanted subjects will receive the Harmony TPV 22 or Harmony mTPV 25 device. This phase allows up to 45 subjects implanted with TPV 22 in the United States and Canada, and up to 84 subjects implanted with mTPV 25 in the United States. The Post Approval Phase (PAS) addendum is a prospective, multi-center, non-randomized, post-market study to evaluate the safety and effectiveness of the Harmony TPV system in the United States. All implanted subjects have been implanted with the Harmony TPV 22 or Harmony mTPV 25 device during the pivotal or CAS phase of the study. The PAS addendum extends follow-up from five years to ten years for consenting subjects.

Official Title
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The Medtronic Harmony™ Transcatheter Pulmonary Valve Clinical Study

Conditions
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Congenital Heart Disease, Tetrology of Fallot, RVOT Anomaly, Pulmonary Regurgitation

Intervention / Treatment
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* Device: Harmony TPV System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has severe pulmonary regurgitation as assessed via echocardiography or CMR determined PR fraction >/= 30% Subject has clinical indication for surgical placement of an RV-PA conduit or bioprosthetic pulmonary valve Subject is willing to consent to participate Exclusion Criteria: Patients with right ventricular outflow tract obstruction (RVOTO) lesions surgically treated with an RV-to-PA conduit implant RVOT anatomy or morphology that is unfavorable for device anchoring Positive pregnancy test Life expectancy of less than 1 year
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 |
| --- | --- |
| Other: Harmony TPV System<br>Intervention Device: Harmony Transcatheter Pulmonary Valves and Delivery Systems | Device: Harmony TPV System<br>* The Harmony™ TPV (Model NTPV0022) is comprised of a 22mm porcine pericardium valve, sewn to a polyester-covered nitinol frame. The Harmony TPV 25 and mTPV 25 (Model HTPV254952 and HTPV254252, respectively) is comprised of a 25mm porcine pericardium valve, sewn to a polyester covered asymmetrical hourglass nitinol frame with larger diameter inflow and outflow as well as shorter length compared to TPV 22 (Harmony TPV 25 Model HTPV254952 is not applicable for Continued Clinical Experience). The Harmony Delivery System (DS) for the TPV 22, TPV 25, and mTPV 25 (NTPVDS0022 and HTPVDS0025) are all 25 Fr delivery systems using a coil loading catheter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom From Procedure- or Device-related Mortality at 30 Days. | The primary safety endpoint is point estimate of freedom from procedure or device-related mortality rate at 30 days post procedure. | 30 days | 
| Number of Participants With Acceptable Hemodynamic Function Composite at 6 Months | Defined as: Mean RVOT gradient as measured by continuous-wave Doppler ≤40 mmHg -AND- Pulmonary regurgitant fraction as measured by magnetic resonance imaging <20% | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Technical Success at Exit From Catheterization Lab/Operating Room (OR) | Technical success at exit from catheterization lab/operating room (OR), as defined as: No device- or procedural-related mortality, with Successful access, delivery and retrieval of the delivery system, and Deployment and correct positioning (including minor repositioning if needed) of the single intended device, and No need for additional unplanned or emergency surgery or re-intervention related to the device or access procedure | At exit from catheterization lab/operating room (OR) | 
| Device Success Out to 5 Years | Device success is defined as: No device- or procedural-related mortality, with Original intended device in place, and No additional surgical or interventional procedures related to access or the device since completion of the original procedure (i.e., exit from the catheterization lab), and Intended performance of the device, as defined as: Structural performance: No migration, embolization, detachment, major stent fracture, hemolysis, thrombosis, endocarditis, and Hemodynamic performance: Relief of insufficiency (PR < moderate) without producing the opposite (mean RVOT gradient > 40 mmHg) as measured by continuous wave Doppler, and Absence of para-device complications, as defined by: PVL = moderate, or Erosion, or RVOT or PA rupture | 5 years | 
| Number of Participants With Procedural Success at 30 Days | Procedural success is defined as: Device success at 30 days, and None of the following device- or procedure-related serious adverse events: Life-threatening major bleed Major vascular or cardiac structural complications required unplanned reintervention or surgery Stage 2 or 3 acute kidney injury (AKI) (includes new dialysis) Pulmonary embolism Severe heart failure (HF) or hypotension requiring IV inotrope, ultrafiltration, or mechanical circulatory support Prolonged intubation >48 hours | 30 days | 
| Freedom From TPV Dysfunction Out to 5 Years | TPV dysfunction is defined as any one of the following: RVOT reoperation for device-related reasons Catheter re-intervention of TPV Hemodynamic dysfunction of the TPV (moderate or greater pulmonary regurgitation, and/or a mean RVOT gradient >40 mmHg) | 5 years (5 year data has an anticipated reporting date of April 2025) | 
| Assessment of Safety | All procedure-related serious adverse events. All device-related serious adverse events. Death (all-cause, procedural, and device-related). | Ongoing | 
| Characterization of Quality of Life Scores Out to 5 Years | Quality of life score over time will be assessed by the SF-36 at pre-implant, 1 month post-implant, 6 months post-implant, 1 year post-implant, 2 years post-implant, and 3 years. The analysis cohort will be the implanted > 24 hours cohort. Minimum score of 0 and maximum score of 100 is possible. Higher values are considered to be a better outcome. | Baseline, 30 Day, 6 Month, 1 Year, 2 Year, 3 Year | 
| Characterization of Right Ventricle Remodeling Following TPV Implant | Right ventricle remodeling will be assessed via CMR at pre-implant and 6 months post-implant. The analysis cohort will be implanted longer than 24 hours cohort. The characterization will be made using right ventricular end diastolic volume (ml). | Baseline, 6 Month | 
| Characterization of Quality of Life Scores Out to 5 Years | Quality of life score over time will be assessed by the SF-36 at 4 & 5 years. The analysis cohort will be the implanted > 24 hours cohort. Minimum score of 0 and maximum score of 100 is possible. Higher values are considered to be a better outcome. | 4 Year, 5 Year (4 & 5 year data has an anticipated reporting date of April 2025) | 
| Characterization of Right Ventricle Remodeling Following TPV Implant | Right ventricle remodeling will be assessed via CMR at 2 years post- implant and 5 years post-implant. The analysis cohort will be implanted longer than 24 hours cohort. The characterization will be made using right ventricular end diastolic volume (ml). | 2 Year, 5 Year (2 & 5 year data has an anticipated reporting date of April 2025) |