(P019) PRE-CLINICAL EVALUATION OF A THIRD GENERATION ABSORBABLE ANTIBACTERIAL ENVELOPE

Background: The TYRX absorbable antibacterial envelope has been shown to stabilize implantable cardiac devices and reduce infection. A third-generation envelope (T3) has been developed to reduce surface roughness with a redesigned, multifilament mesh and an enhanced form factor. It maintains the identical polymer coating and antibiotic concentrations as the currently available second-generation envelope (T2). The purpose of this evaluation was to compare the drug elution profile, bacterial challenge efficacy, stabilization performance (device migration and rotation), and absorption of T3 vs. T2.

METHODS AND RESULTS: T3 vs. T2 drug elution was assessed using an accelerated dissolution method in vitro. Elution was also assessed in vivo (rabbit model) to ensure antibiotic concentrations were above minimal inhibitory concentration (MIC) at 2hr post-implant and sustained through 7 days. Efficacy against gram+ and gram- bacteria was assessed in vivo; 6 rabbits received two cardiac implantable electronic device (CIED) implants, with and without T3 envelopes, and underwent bacterial challenge. Signs of infection were assessed via macroscopic observations and microbial recovery procedures at day 7. For stabilization (migration and rotation) evaluation, 5 sheep were implanted with 6 devices each (either cardiac or neurostimulators in T3 or T2 envelopes). CT images were obtained at implant and term (week 9 or 12). Pre-specified acceptance criteria were < 83 mm for migration and < 90 degrees for rotation. Envelope absorption was assessed visually via gross pathology. Elution curves were equivalent based on similarity factor values (f2) of ≥50 per FDA guidance (range 76-84). T3 eluted both antibiotics above MIC at 2hr post-implant and through 7 days, consistent with historical T2 performance. Bacterial challenge showed a statistically significant reduction (p < 0.05) in infection when envelopes (T2 or T3) were used (Table). Acceptance criteria for both migration and rotation were met. Average device migration was 5.5±3.5 mm for T3 (n=14), and 9.9±7.9 mm for T2 (n=15) (p < 0.05 for non-inferiority). Device rotation was 18.9±11.4 (T3) vs. 17.6±15.1 degrees (T2) and was not statistically different between groups (p=0.79). Gross pathology confirmed absence of luminal mesh remainders and no observable differences in peri-device fibrosis at week 9 or 12 (Figure).

Conclusion: The T3 absorbable antibacterial envelope demonstrated equivalent pre-clinical performance compared to the T2 envelope as antibiotic elution curves were similar, elution was sustained at concentrations above MIC for 7 days, infection rates were significantly reduced compared to no envelope, and acceptance criteria for migration, rotation, and absorption were met.