CLINICAL DATA Melody™ Transcatheter Pulmonary Valve (TPV) Replacement

UNMATCHED CLINICAL EVIDENCE

The Melody valve is the longest studied transcatheter pulmonary valve (TPV), with the largest body of clinical evidence. Accumulated data have consistently demonstrated excellent clinical results, including high rates of freedom from surgical reoperation, confirming the Melody TPV safely and effectively delays the need for surgical conduit exchange.

U.S. IDE STUDY

Prospective, non-randomized investigational study conducted at five centers in the United States. One hundred fifty (150) subjects implanted between January 2007 and January 2010; patients will be followed for 10 years. Data presented are interim results current through June 2016.

U.S. Post Approval Study (PAS)

Prospective, non-randomized study conducted at 10 centers in the United States. One hundred (100) subjects implanted between July 2010 and July 2012; patients will be followed for 5 years. Data presented are interim results through June 2016.

European and Canadian Post-Market Surveillance Study (PMSS)

Prospective, non-randomized study conducted at seven centers in Europe and Canada. Sixty-three (63) subjects implanted between October 2007 and April 2009; patients were followed for 5 years. Data presented are final results as of August 2016.

Study # of Centers # of Patients First Implant Last Implant Mean Length
of Follow-up
US IDE 5 150 2007 2010 6.1 ± 1.7 years
US PAS 10 100 2010 2012 3.8 ± 1.2 years
EU/CA PMSS 7 63 2007 2009 4.7 ± 1.1 years

U.S. Investigational Device Exemption Study (IDE) | U.S. Post Approval Study (PAS) | EU/CA Post-Market Surveillance Study (PMSS)

DELAYS PATIENT’S NEXT SURGICAL INTERVENTION

Low rates of surgical conduit reoperation out to 8 years.

Low rates of surgical conduit reoperation out to 8 years

FREEDOM FROM CATHETER RE-INTERVENTION

Freedom from catheter-based re-intervention on the TPV was greater than 78% out to 8 years.

Rates of feedom from cathetre-based re-intervention on the TPV

LOW RVOT GRADIENTS

Following Melody TPV implant the mean right ventricle outflow tract (RVOT) gradients decreased and remained consistent throughout follow-up in all three studies.

Mean RVOT Gradient
By Time Interval
Baseline 1 Year 3 Year 5 Year 7 Year
US IDE
(N=149)
32.1 ± 13.9 18.7 ± 9.1 17.6 ± 7.9 17.5 ± 8.4 17.9 ± 9.8
US PAS
(N=99)
33.4 ± 14.1 15.1 ± 7.1 16.7 ± 10.8 14.4 ± 12.6 --
EU/CA PMSS
(N=62)
37.7 ± 12.1 17.9 ± 9.2 17.3 ± 8.4 17.3 ± 9.7 -

MINIMAL REGURGITATION

The majority of subjects in all three studies had moderate or severe pulmonary regurgitation at baseline. Throughout follow-up, the majority of subjects had no more than trace pulmonary regurgitation.

Rates of regurgitation throughout follow-up

PROCEDURAL SUCCESS AND STRONG SAFETY PROFILE

The safety profile of the Melody TPV has remained unchanged through the longer-term follow-up data and broader implanter base in the Medtronic studies, demonstrated by the low rates of procedural and device-related serious adverse events.

HIGH RATES OF PROCEDURAL SUCCESS

Studies show consistently high rates of successful valve implantation, including strong hemodynamics and low incidence of procedural adverse events.

Procedural success is a composite outcome defined as:

  • Melody TPV was successfully delivered to the intended location.
  • RV-PA peak-to-peak gradient (measured in the catheterization lab) less than 35 mmHg post implant
  • Less than mild pulmonary regurgitation
  • Free of explant at 24 hours post implant
Study Procedural Success
US IDE (N=149) 94.7%
US PAS (N=99) 92.1%
EU/CA PMSS (N=62) 88.7%

LOW RATES OF DEVICE-RELATED SERIOUS ADVERSE EVENTS

The safety profile of the Melody valve remains out to 7 years as evidence by low rates of serious device-related adverse events across all studies.

Event

US IDE

Freedom from event at 7 years (CI) (N=149)

US PAS

Freedom from event at 5 years (CI) (N=99)

EU/CA PMSS

Freedom from event at 5 years (CI) (N=62)

Stent Fracture: Major 83.6% 
(75.7%, 89.2%)
91.0%
(81.3%, 95.8%)
91.6% 
(81.1%, 96.4%)
Valve Dysfunction: Stenosis 79.3% 
(70.8%, 85.7%)
86.1%
(76.1%, 92.1%)
82.3% 
(69.5%, 90.1%)
Valve Dysfunction: Regurgitation 99.3% 
(95.4%, 99.9%)
88.7% 
(75.8%, 94.9%)
98.3% 
(89.4%, 99.7%)
Prosthetic Valve Endocarditis 89.2% 
(79.7%, 94.4%)
84.9% 
(73.9%, 91.5%)
93.2%
(82.6%, 97.4%)
Embolization of the TPV 100.0% 
(NA)
100.0% 
(NA)
100.0% 
(NA)

IMPROVES FUNCTIONAL STATUS

At baseline, the majority of subjects in all three studies were NYHA class II/III. Following Melody TPV implant, the majority of subjects were in NYHA class I, which remained consistent during follow-up.

Following Melody TPV implant, the majority of subjects were in NYHA class I

Approved for Use in Dysfunctional Surgical Bioprosthetic Pulmonary Valves

Data pooled from two U.S. prospective studies that included both failed conduits and BPVs and one retrospective study assessing Melody in dysfunctional BPVs only, demonstrated safety and effectiveness in restoring pulmonary valve function without open heart surgery.

The following outcomes demonstrate the safety and effectiveness of the Melody TPV implanted in a bioprosthetic pulmonary valve (BPV) restoring pulmonary valve competency while delaying the need for surgical intervention.

Variable

Bioprosthesis (n=125)

Number of

Subjects in the Analysis

Bioprosthesis (n=125)

Endpoint Rate
(95% CI)

RVOT Conduit (n=225)

Number of

Subjects in the Analysis

RVOT Conduit (n=225)

Endpoint Rate
(95% CI)

Procedural
success
117 88.9%
(82.9%, 93.3%)
225 93.8%
(90.4%, 96.2%)
Procedure-related serious
AE at 1 year
125 4.0%
(2.6%, 10.1%)
225 12.4%
(12.0%, 20.0%)
Device-related
serious AE at 1 year
125 2.4%
(0.6%, 6.0%)
225 16.0%
(16.7%, 25.6%)

The confidence intervals are exact (Clopper-Pearson) confidence intervals for the binomial proportion.

Variable

Bioprosthesis (n=125)

Number of
Subjects in the
Analysis

Bioprosthesis (n=125)

1-year
Freedom from Rate
(95% CI)

RVOT Conduit (n=225)

Number of
Subjects in the
Analysis

RVOT Conduit (n=225)

1-year
Freedom from Rate
(95% CI)

TPV
Dysfunction
125 97.4%
(90.0%, 99.4%)
223 94.1%
(90.1%, 96.6%)
Reoperation 125 100.0%
(NA)
223 98.6%
(95.9%, 99.6%)
Reintervention 125 100.0%
(NA)
223 98.2%
(95.2%, 99.3%)
 
All-Cause Mortality
125 100.0%
(NA)
223 99.6%
(96.8%, 99.9%)
 
Major Stent
Fracture
125 100.0%
(NA)
223 97.7%
(94.6%, 99.1%)
 Endocarditis 125 100.0%
(NA)
223 97.3%
(94.0%, 98.8%)

The cumulative probability of event free estimate is based on the Kaplan-Meier method.
The 95% confidence interval is the loglog transformed 95% Confidence Interval (CI) using the Peto standard error.