13
approach). Patients in the treatment cohort of Cohort B received an Edwards SAPIEN XT valve with the
N delivery system (transfemoral). The randomized sample size was set to 500 patients.
Enrollment is complete and patients have reached at least 1 year of follow-up.
Cohort B of The Placement of Aortic Transcatheter Valves Trial II (PARTNER II) included registries for the
transfemoral delivery of the SAPIEN XT valve. These registries include the following:
•
NR3: Registry for Transcatheter Heart Valve in Aortic Surgical Valve Implantation (THV-SV).
Patients with failing aortic bioprosthetic surgical valve with a surgical mortality or major morbidity
≥ 50% and meeting the sizing requirements for 23 mm or 26 mm SAPIEN XT valve.
•
NR5 (29 mm / Transfemoral / Inoperable)
is an Inoperable Transfemoral Registry for the delivery
of 29 mm SAPIEN XT valve in
≥ 7 mm femoral arteries.
Following completion of enrollment in the nested registries, the FDA approved continued access
enrollment in the nested registries (CANRs).
SOURCE Registry XT
The SOURCE Registry XT is an international multi-center prospective, consecutively enrolled,
observational registry. Consecutive patient data have been collected at discharge, 30 days, and
12 months post-implant, and will be collected annually thereafter up to 5 years post-implant.
Results of Cohort B
The primary endpoint of Cohort B of the PARTNER II trial was met. At 1 year the non-hierarchical composite
of all-cause mortality, disabling strokes, and re-hospitalizations was similar (p non-inferiority = 0.0037). At
30 days, all-cause mortality and major strokes were similar (mortality: SAPIEN valve 5.1% vs. SAPIEN XT
valve 3.5%; major strokes: SAPIEN valve 3.0% vs. SAPIEN XT valve 3.2%, p>0.9999).
The Edwards SAPIEN XT cohort was associated with a reduction in anesthesia time (p=0.0196), cath lab
time (p=0.0094), multiple valve implants (p=0.1534), aborted procedures (p=0.0585), and the need for
hemodynamic support (p=0.0637).
The trial showed that there was a reduction in the Edwards SAPIEN XT cohort as compared to
Edwards SAPIEN cohort for the following complications: major vascular complications involving dissection
(from 9.2% to 4.3%, p=0.0195), perforation (from 4.8% to 0.7%, p=0.0031), and infection (from 5.5% to
1.8%, p=0.0163).
Secondary endpoints for the study included days alive and out of the hospital (DAOH), NYHA, 6MWT,
valve area (EOA), and total aortic regurgitation at one year as well as 6MWT improvement from baseline
to 1 year and device success.
Mean adjusted days alive and out of the hospital (DAOH) at 1 year: In the ITT population, the mean
adjusted days alive and out of the hospital (DAOH) was 299.2 ± 111.4 days for the SAPIEN cohort and
302.7 ± 108.7 days for the SAPIEN XT cohort at 1 year. The difference between cohorts was 3.5 days
(two sided 95% CI 1.8, 5.2), p< 0.0001.
NYHA at 1 year: In the SAPIEN cohort, mean NYHA was 3.5 ± 0.6 at baseline and 1.8 ± 0.8 at 1 year
which constituted a reduction of 1.7 ± 0.9. In the SAPIEN XT cohort, mean NYHA was 3.4 ± 0.6 at
baseline and 1.7 ± 0.7 at 1 year which was a mean decrease of 1.8 ± 0.9. The difference between cohorts
was -0.13, (two sided 95% CI -0.32, 0.06), p< 0.0001. Figure 14 illustrates the NYHA classification by visit
for the ITT population.
6MWT at 1 year: Hypothesis testing was based on a difference of 70 meters which is considered clinically
relevant. The mean 6 minute walk distance (6MWD) at 1 year was 132.3 ± 136.3 meters in the SAPIEN
cohort, and 159.0 ± 138.5 meters in the SAPIEN XT cohort. The difference between cohorts was
26.7 meters (95% CI 24.2, 29.2), p<0.0001.
EOA at 1 year (hypothesis testing was based on a difference of 0.2 cm
2
): In the SAPIEN cohort, mean
EOA was 0.6 ± 0.17 cm
2
at baseline and 1.5 ± 0.40 cm
2
at 1 year, which was an improvement of
0.9 ± 0.38 cm
2
. In the SAPIEN XT cohort, mean EOA was 0.6 ± 0.18 cm
2
at baseline and 1.5 ± 0.43 cm
2
at 1 year, a mean increase of 0.9 ± 0.41 cm
2
. The difference between cohorts in change from baseline to
1 year was -0.01 (95% CI -0.15, 0.13), p=0.0038.
Device success: Device success was defined as successful vascular access, delivery and deployment
and retrieval of delivery system; correct positioning, intended performance (aortic valve area > 1.2 cm
2