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.