METHODS
Study design
This study was a prospective, nonrandomized, single‑arm, postapproval,
multicenter, 8‑year study of the Magna Ease valve (ClinicalTrials.gov
NCT01171625).
The FDA required data from at least 101 patients over 8 years. The study
protocol projected that at least 225 patients would need to be enrolled
at the beginning to achieve the required number at 8-year follow-up and
the study was terminated when this number was reached. The study
protocol complied with ISO 14155:2011; European Medical Device Directive
2007/47/EC; and MedDev 2.12-1, 2.7.4, and 2.12.2. The ICH E6 GCP Good
Clinical Practices was also used for guidance.
Study cohort
Patients were enrolled between October 2007 and December 2012 at 14
investigational sites in Europe, Canada, and the US (Figure 1). Patients
undergoing surgical replacement of their native or prosthetic aortic
valve at participating centers were invited to participate. The
inclusion criteria for this study were: requirement for a replacement
aortic valve, as indicated in the preoperative evaluation; average or
better operative risk; geographically stable and agreeable to attend
follow-up assessments at the hospital of surgical services for at least
8 years; 18 years or older; signed and dated the subject informed
consent form prior to surgery. The study’s exclusion criteria were: any
known non-cardiac life-threatening disease, which will limit the
patient’s life expectancy below 1 year; active endocarditis within the
last 3 months; abnormal calcium metabolism (e.g., chronic renal failure,
hyperparathyroidism); aneurismal aortic degenerative condition (e.g.,
cystic medial necrosis, Marfan’s syndrome); pregnant or lactating;
intravenous drug abuse; current prison inmate; current participant in a
study of an investigational drug or device; requirement for replacement
of a native or prosthetic mitral, tricuspid, or pulmonic valve;
requirement for repair of the mitral or tricuspid valve with the use of
an annuloplasty device; previous enrolment in the study; prior mitral,
tricuspid, or pulmonic valve surgery, which included implantation of a
bioprosthetic valve, mechanical valve, or annuloplasty ring that will
remain in situ. The choice of surgical technique was left to surgeon
discretion.
Follow-up and endpoints
After implantation, patients were followed up at hospital discharge, 6
months, 1 year, and annually thereafter up to 8 years. This report
includes data through to September 14, 2018 when the minimum requirement
of 8-year follow-up for 101 patients had been achieved.
Safety endpoints included death, valve-related death, thromboembolism,
hemorrhage, paravalvular leak, prosthetic valve endocarditis, valve
thrombosis, hemolysis, structural valve deterioration (SVD),
nonstructural valve dysfunction (NSVD), reintervention, and valve
explant. All safety endpoints and serious adverse events were defined as
per Akins et al .[12] and adjudicated by an independent
Clinical Events Committee (CEC).
Effectiveness endpoints included the proportion of patients in New York
Heart Association (NYHA) Functional Class I or II at 8 years, and
hemodynamic performance as assessed by echocardiographic parameters:
effective orifice area (EOA), mean gradient, and aortic regurgitation
(combined paravalvular and central leak) severity. Hemodynamic data were
collected and scored by the individual sites. Collection of these data
at years 3 and 7 was not mandated and therefore not reported.
Data management and statistical
analyses
The investigational sites were responsible for accurate collection and
recording of the clinical data. Edwards Lifesciences, the study sponsor,
monitored and aggregated the clinical data, then analyzed them per the
study protocol and statistical analysis plan. Summary statistics include
absolute and proportional data for categorical variables and mean ±
standard deviation for continuous variables. Early safety events were
defined as those occurring within 30 days of the index procedure and
were reported as the number of patients with an event divided by the
number of implanted patients. Late events represented those occurring
beyond 30 days postoperatively and through 8 years (postoperative day
2,922). Actuarial Kaplan–Meier analyses were undertaken on each of the
safety endpoints and reported with 95% confidence intervals (CI). SAS
version 9.4 was used for all statistical analyses.