Congenital Heart Defects, Dysfunctional Right Ventricular Outflow Tract Conduits
Conditions
Brief summary
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
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.
Interventions
DEVICETranscatheter Pulmonary Valve replacement
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.
Sponsors
Medtronic Cardiovascular
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Freedom From TPV Dysfunction | 5 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Procedural Success | Within 24 Hours post implant | 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 |
| Serious Procedural Adverse Event (AE) | 5 years | 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). |
| Serious Device-related Adverse Event | 5 years | 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). |
| Kaplan-Meier Freedom From Major Stent Fracture at 5 Years | 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. |
| Freedom From TPV Dysfunction at 10 Years | 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). |
| Kaplan-Meier Freedom From Catheter Re-intervention on TPV | 5 years | Catheter Re-intervention is defined as: any catheter-based intervention involving the TPV, including balloon dilatation, stenting, or placement of a second TPV |
| Kaplan-Meier Freedom From Surgical Replacement of the RVOT Conduit | 5 years | Surgical Replacement of the RVOT Conduit is defined as any surgical procedure to repair, alter, or explant the TPV |
| Kaplan-Meier Freedom From Death (All-cause, Procedural and Device-related) | 5 years | Deaths is defined as all-cause, procedural and device-related events at 5 years |
| Functional Assessment (NYHA Classification) | 6 Months | Improvement in Functional Assessment (NYHA Classification) at 6 months post implant. |
| Kaplan-Meier Freedom From Major Stent Fracture at 10 Years | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enrolled Cohort All subjects enrolled | 171 |
| Total | 171 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Further testing contraindicated implant | 17 |
| Overall Study | Not Catheterized | 4 |
Baseline characteristics
| Characteristic | Enrolled Cohort |
|---|---|
| Age, Continuous | 21.8 years STANDARD_DEVIATION 9.8 |
| Region of Enrollment United States | 171 participants |
| Sex: Female, Male Female | 64 Participants |
| Sex: Female, Male Male | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 167 |
| other Total, other adverse events | 112 / 167 |
| serious Total, serious adverse events | 106 / 167 |
Outcome results
Primary
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
Time frame: 5 years
Population: The Implanted \>24 hours cohort consists of all subjects who had a Melody TPV implanted which remained implanted for greater than 24 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Kaplan-Meier Freedom From TPV Dysfunction | 72.9 percentage of subjects |
p-value: <0.0001Z test
Secondary
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).
Time frame: 10 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Freedom From TPV Dysfunction at 10 Years | 52.9 Percentage of subjects |
Secondary
Functional Assessment (NYHA Classification)
Improvement in Functional Assessment (NYHA Classification) at 6 months post implant.
Time frame: 6 Months
Population: The Implanted \>24 hours cohort consists of all subjects who had a Melody TPV implanted which remained implanted for greater than 24 hours and had paired data from pre-implant to 6 months post-implant.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Implanted >24 Hour Cohort | Functional Assessment (NYHA Classification) | Improved | 102 Participants |
| Implanted >24 Hour Cohort | Functional Assessment (NYHA Classification) | No Change | 39 Participants |
| Implanted >24 Hour Cohort | Functional Assessment (NYHA Classification) | Worsened | 1 Participants |
| Implanted >24 Hour Cohort | Functional Assessment (NYHA Classification) | Died | 1 Participants |
Secondary
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
Time frame: 10 years
Population: The Implanted \>24 hours cohort consists of all subjects who had a Melody TPV implanted which remained implanted for greater than 24 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Kaplan-Meier Freedom From Catheter Re-intervention on TPV | 73.1 percentage of subjects |
Secondary
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
Time frame: 5 years
Population: The Implanted \>24 hours cohort consists of all subjects who had a Melody TPV implanted which remained implanted for greater than 24 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Kaplan-Meier Freedom From Catheter Re-intervention on TPV | 81 percentage of subjects |
Secondary
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
Time frame: 10 years
Population: The catheterized cohort consists of all subjects who underwent catheterization for possible implantation of the Melody TPV.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Kaplan-Meier Freedom From Death (All-cause, Procedural and Device-related) | 90.2 percentage of subjects |
Secondary
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
Time frame: 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Kaplan-Meier Freedom From Death (All-cause, Procedural and Device-related) | 96.5 percentage of subjects |
Secondary
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.
Time frame: 10 years
Population: The Implanted \>24 hours cohort consists of all subjects who had a Melody TPV implanted which remained implanted for greater than 24 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Kaplan-Meier Freedom From Major Stent Fracture at 10 Years | 83.7 percentage of subjects |
Secondary
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.
Time frame: 5 years
Population: The Implanted \>24 hours cohort consists of all subjects who had a Melody TPV implanted which remained implanted for greater than 24 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Kaplan-Meier Freedom From Major Stent Fracture at 5 Years | 84.3 percentage of subjects |
Secondary
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
Time frame: 5 years
Population: The Implanted \>24 hours cohort consists of all subjects who had a Melody TPV implanted which remained implanted for greater than 24 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Kaplan-Meier Freedom From Surgical Replacement of the RVOT Conduit | 92.2 percentage of subjects |
Secondary
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
Time frame: 10 years
Population: The Implanted \>24 hours cohort consists of all subjects who had a Melody TPV implanted which remained implanted for greater than 24 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Kaplan-Meier Freedom From Surgical Replacement of the RVOT Conduit | 78.9 percentage of subjects |
Secondary
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
Time frame: Within 24 Hours post implant
Population: The attempted implant cohort consists of all subjects who underwent catheterization and a Melody TPV implantation was attempted (Melody TPV valve opened).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Procedural Success | 94.7 percentage of subjects |
Secondary
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).
Time frame: 10 years
Population: The implanted cohort consists of all subjects who underwent catheterization and a Melody TPV was implanted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Serious Device-related Adverse Event | 41.3 percentage of subjects |
Secondary
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).
Time frame: 5 years
Population: The implanted cohort consists of all subjects who underwent catheterization and a Melody TPV was implanted.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Serious Device-related Adverse Event | 28 Percentage of subjects |
Secondary
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).
Time frame: 10 years
Population: The catheterized cohort consists of all subjects who underwent catheterization for possible implantation of the Melody TPV.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Serious Procedural Adverse Event (AE) | 13.2 percentage of subjects |
Secondary
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).
Time frame: 5 years
Population: The catheterized cohort consists of all subjects who underwent catheterization for possible implantation of the Melody TPV.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implanted >24 Hour Cohort | Serious Procedural Adverse Event (AE) | 12.6 Percent of subjects |