Efficacy and Safety of a Parylene-Coated Occluder for Atrial Septal Defect: A Prospective, Multi-Center, Randomized Controlled Clinical Trial
Atrial septal defect (ASD) is a common congenital heart disease that can lead to significant morbidity if left untreated. Percutaneous transcatheter closure of ASD has become a well-established and widely used treatment strategy over the past three decades, offering advantages such as avoidance of cardiopulmonary bypass, shorter hospitalization, and reduced post-procedural complications compared to surgical thoracotomy. However, the majority of devices used for percutaneous ASD closure are made of nitinol, an alloy composed of nickel and titanium. While nitinol devices are highly effective, concerns have been raised about the potential release of nickel into the bloodstream following implantation, which may lead to adverse effects such as allergic reactions, cytotoxicity, and carcinogenicity. To address these concerns, a parylene-coated occluder has been developed to prevent nickel release while maintaining the device’s structural and functional properties. This study aimed to evaluate the efficacy and safety of the parylene-coated occluder in comparison to a traditional nitinol-containing device through a prospective, multi-center, randomized controlled clinical trial.
Study Design and Methods
The study was conducted as a prospective, multi-center, blind evaluation, randomized controlled clinical trial across three hospitals in China: Beijing Fuwai Hospital, Henan Provincial People’s Hospital, and West China Hospital of Sichuan University. The trial was designed to compare the efficacy and safety of a parylene-coated ASD occluder with a traditional uncoated ASD occluder. A non-inferiority design was employed to demonstrate that the therapeutic effect of the parylene-coated device was not inferior to that of the traditional device.
A total of 108 patients with secundum ASD were enrolled and randomly assigned to either the trial group (n = 54), which received the parylene-coated occluder, or the control group (n = 54), which received the traditional uncoated occluder. The inclusion criteria included patients aged 3 to 60 years with a clinical diagnosis of secundum ASD, sufficient defect margins on echocardiography, and agreement to undergo regular follow-up evaluations. Exclusion criteria included ASD with other intracardiac malformations requiring surgical correction, severe pulmonary hypertension with a bidirectional shunt, active endocarditis or systemic infections, and intolerance to oral aspirin.
The primary efficacy endpoint was the successful closure rate of the ASD at six months post-implantation, assessed using echocardiography by an independent third party blinded to the treatment groups. Successful closure was defined as no residual shunt or only a small residual shunt (shunt beam diameter ≤ 2 mm) at the closure site. Secondary endpoints included serum nickel levels, liver and kidney function, and the occurrence of adverse events such as device displacement, death, or severe complications requiring surgical or interventional treatment.
Device Description and Procedure
The parylene-coated ASD occluder was braided from parylene-coated nitinol wires into two round discs connected by a 3 to 4 mm waist. The left atrial disc was 12 to 16 mm larger than the waist, and the right atrial disc was 8 to 10 mm larger. The device was filled with three layers of polyester or a combination of polyester and expanded polytetrafluoroethylene to ensure complete occlusion. The device was available in various models with waist diameters ranging from 4 to 44 mm and could be delivered using the same delivery system (6–14F sheath) as the traditional uncoated occluder.
The procedure for device implantation was standardized across both groups. Under local anesthesia (general anesthesia for children under 10 years), the right femoral vein was punctulated, and routine right cardiac catheterization was performed. Transthoracic or transesophageal echocardiography was used to assess the size, location, and relationship of the ASD to surrounding tissues. An appropriately sized occluder was selected and delivered to the left atrium via a delivery sheath. The left atrial disc was extruded, and the sheath and delivery wire were withdrawn until resistance was met, indicating apposition of the left atrial disc to the atrial septum. The right atrial disc was then fully deployed, and the occluder was released by counterclockwise rotation of the delivery wire.
Results
At six months post-implantation, successful ASD closure was achieved in 52 of 53 patients (98.11%) in both the trial and control groups, based on per-protocol set analysis. The absolute value of the lower limit of the 95% confidence interval (CI) for the difference in success rates between the two groups was 4.90%, which was less than the pre-specified non-inferiority margin of 8%. This confirmed that the efficacy of the parylene-coated occluder was non-inferior to that of the traditional device.
In the control group, serum nickel levels were significantly increased at two weeks post-implantation, peaking at one month before gradually decreasing to baseline levels by six months. In contrast, the trial group showed no significant change in serum nickel levels before and after device implantation, indicating that the parylene coating effectively prevented nickel release.
No deaths or severe complications occurred during the six-month follow-up period in either group. One patient in each group experienced device displacement on the first day post-implantation, attributed to errors in pre-operative ultrasonographic measurements of the defect size and margins. Two patients in the trial group developed incomplete right bundle branch block, but no other adverse events were reported.
Discussion
The results of this study demonstrate that the parylene-coated ASD occluder is a safe and effective alternative to traditional nitinol-containing devices for percutaneous closure of secundum ASD. The high success rate of closure (98.11%) in both groups highlights the non-inferiority of the parylene-coated device. Moreover, the prevention of nickel release in the trial group addresses a significant concern associated with nitinol devices, particularly in patients with nickel allergies or sensitivities.
Previous studies have documented the release of nickel following implantation of nitinol-containing devices, with serum nickel levels peaking at one to three months post-implantation and gradually returning to baseline over time. Nickel release has been associated with systemic adverse effects, including allergic reactions, pericarditis, and increased migraine frequency. In severe cases, refractory symptoms may necessitate surgical removal of the device. The parylene-coated occluder, by preventing nickel release, offers a potential solution to these issues, particularly for patients with known nickel allergies.
The parylene coating used in this study is a thermoplastic polymer material with excellent chemical inertness and biocompatibility, certified by the Food and Drug Administration. Its application to nitinol wires not only prevents nickel release but also maintains the super-elastic and shape-memory properties of nitinol, which are critical for the device’s performance. The results of this study are consistent with previous findings on platinum-coated and ceramic-coated devices, which also demonstrated reduced nickel release while maintaining device efficacy.
Limitations
While this study provides strong evidence for the efficacy and safety of the parylene-coated ASD occluder, it has several limitations. First, the follow-up period was relatively short (six months), and long-term data on device performance and nickel release are not available. Second, the study did not assess the baseline serum nickel levels of the general population, which could provide additional context for the observed changes in the control group. Third, although the study was conducted across three centers, the majority of patients (60%) were recruited from a single center, which may limit the generalizability of the findings.
Conclusions
The parylene-coated ASD occluder is a safe and effective alternative to traditional nitinol-containing devices for percutaneous closure of secundum ASD. Its non-inferior efficacy and ability to prevent nickel release make it a viable option for patients, particularly those with nickel allergies. Further studies with longer follow-up periods and broader patient populations are needed to confirm these findings and assess the long-term safety and performance of the parylene-coated occluder.
doi.org/10.1097/CM9.0000000000001865
Was this helpful?
0 / 0