Melody Transcatheter Pulmonary Valve Study: Post Approval Study of the Investigational Device Exemption Cohort

Study Overview
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Brief Summary
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The primary objective is to confirm the long-term functionality of implantation of the Medtronic Melody TPV at 5 years is no worse than the historical control established through literature review. The secondary objectives are to evaluate long-term functionality at 10 years and to assess safety, procedural success, and clinical utility of transcatheter implantation of the Melody TPV.

Detailed Description
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The primary objective is to confirm the long-term functionality of implantation of the Medtronic Melody TPV at 5 years is no worse than the historical control established through literature review. The secondary objectives is to evaluate long-term functionality at 10 years and to assess safety, procedural success, and clinical utility of transcatheter implantation of the Melody TPV.

Official Title
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Implantation of the Medtronic Melody Transcatheter Pulmonary Valve in Patients With Dysfunctional Right Ventricular Outflow Tract (RVOT) Conduits: A Feasibility Study

Conditions
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Congenital Heart Defects, Dysfunctional Right Ventricular Outflow Tract Conduits

Intervention / Treatment
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* Device: Transcatheter Pulmonary Valve replacement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 5 years of age Weight greater than or equal to 30 kilograms Existence of a full (circumferential) RVOT conduit that was equal to or greater than 16 mm in diameter when originally implanted, or a stented bioprosthesis with a rigid circumferential sewing ring in the RVOT that has an internal diameter greater than or equal to 18 mm and less than or equal to 22 mm when originally implanted. Any of the following by transthoracic echocardiography: For patients in New York Heart Association (NYHA) Classification II, III, or IV: Moderate (3+) or severe (4+) pulmonary regurgitation AND/OR Mean RVOT gradient greater than or equal to 35 mmHg For patients in NYHA Classification I:Severe (4+) pulmonary regurgitation with RV dilatation or dysfunction AND/OR Mean RVOT gradient greater or equal to 40 mmHg Exclusion Criteria: Active endocarditis Major or progressive non-cardiac disease (liver failure, renal failure, cancer)that has a life expectancy of less than one year Patient or guardian unwilling or unable to provide written informed consent or comply with follow-up requirements Obstruction of the central veins (including the superior and inferior vena cava, bilateral iliac veins) such that the delivery system cannot be advanced to the heart via transvenous approach from either femoral vein or internal jugular vein Positive urine or serum pregnancy test 24 hours prior to procedure in female patients of child bearing potential Known intravenous drug abuse

Ages Eligible for Study
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Minimum Age: 5 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: Melody TPV Implant<br>Melody Transcatheter Pulmonary Valve implanted into a dysfunctional RVOT Conduit. | Device: Transcatheter Pulmonary Valve replacement<br>* Transcatheter valve implantation into a RVOT conduit in patients with complex congenital heart defects where the conduit has become dysfunctional and where the patient needs invasive intervention.<br>* Other names: Melody Transcatheter Pulmonary Valve;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan-Meier Freedom From TPV Dysfunction | To assess whether long-term functionality of implantation of the Medtronic Melody TPV at 5 years is no worse than the historical control established through literature review. This study is designed to test the null hypothesis that the true freedom from TPV dysfunction at 5 years after Melody implantation (PMelody) is less than or equal to 36% (PControl). To reject the null hypothesis means that freedom from TPV dysfunction at 5 years after Melody implantation (PMelody) is greater than 36% (PControl). The null (H0) and alternative (HA) hypotheses are written as follows:H0: PMelody ≤ PControl and HA: PMelody > PControl. TPV dysfunction is a composite outcome defined as the following: Hemodynamic dysfunction of the TPV Moderate or greater pulmonary regurgitation, and/or Mean Right Ventricular Outflow Tract (RVOT) gradient greater than 40 mmHg RVOT reoperation for conduit dysfunction or device-related reasons Catheter re-intervention on the TPV | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom From TPV Dysfunction at 10 Years | The outcome measure for this objective is TPV dysfunction, which is a composite outcome defined as RVOT reoperation for conduit dysfunction or device-related reasons, catheter re-intervention on the TPV, or hemodynamic dysfunction of the TPV (moderate or greater pulmonary regurgitation, and/or a mean RVOT gradient greater than 40 mmHg). | 10 years | 
| Procedural Success | Procedural success is a composite outcome defined as: Melody TPV fixated within the desired location Right Ventricle (RV) - Pulmonary Artery (PA) peak-to-peak gradient (measured in the catheterization lab) less than 35 mmHg post-implant Less than mild pulmonary regurgitation by angiography post-implant Free of explant at 24 hours post-implant | Within 24 Hours post implant | 
| Serious Procedural Adverse Event (AE) | A procedure-related event is defined as an event that is associated with the implant procedure by the chronology or physiology and was caused by the implant procedure (e.g. rupture of the conduit or damage to an intra-cardiac or intravascular structure by the delivery system). | 5 years | 
| Serious Procedural Adverse Event (AE) | A procedure-related event is defined as an event that is associated with the implant procedure by the chronology or physiology and was caused by the implant procedure (e.g. rupture of the conduit or damage to an intra-cardiac or intravascular structure by the delivery system). | 10 years | 
| Serious Device-related Adverse Event | A device-related event is defined as an event that is associated with the TPV by the chronology or physiology and was caused by the the TPV (e.g. embolization of the TPV and any adverse events which follow). | 5 years | 
| Serious Device-related Adverse Event | A device-related event is defined as an event that is associated with the TPV by the chronology or physiology and was caused by the the TPV (e.g. embolization of the TPV and any adverse events which follow). | 10 years | 
| Kaplan-Meier Freedom From Major Stent Fracture at 5 Years | Major stent fracture is defined as a stent fracture requiring intervention to prevent permanent impairment of a body function or permanent damage to a body structure. | 5 years | 
| Kaplan-Meier Freedom From Major Stent Fracture at 10 Years | Major stent fracture is defined as a stent fracture requiring intervention to prevent permanent impairment of a body function or permanent damage to a body structure. | 10 years | 
| Kaplan-Meier Freedom From Catheter Re-intervention on TPV | Catheter Re-intervention is defined as: any catheter-based intervention involving the TPV, including balloon dilatation, stenting, or placement of a second TPV | 5 years | 
| Kaplan-Meier Freedom From Catheter Re-intervention on TPV | Catheter Re-intervention is defined as: any catheter-based intervention involving the TPV, including balloon dilatation, stenting, or placement of a second TPV | 10 years | 
| Kaplan-Meier Freedom From Surgical Replacement of the RVOT Conduit | Surgical Replacement of the RVOT Conduit is defined as any surgical procedure to repair, alter, or explant the TPV | 5 years | 
| Kaplan-Meier Freedom From Surgical Replacement of the RVOT Conduit | Surgical Replacement of the RVOT Conduit is defined as any surgical procedure to repair, alter, or explant the TPV | 10 years | 
| Kaplan-Meier Freedom From Death (All-cause, Procedural and Device-related) | Deaths is defined as all-cause, procedural and device-related events at 5 years | 5 years | 
| Kaplan-Meier Freedom From Death (All-cause, Procedural and Device-related) | Deaths is defined as all-cause, procedural and device-related events at 10 years | 10 years | 
| Functional Assessment (NYHA Classification) | Improvement in Functional Assessment (NYHA Classification) at 6 months post implant. | 6 Months |