Bioabsorbable steroid-releasing implants in the frontal sinus ostia: a pooled analysis.

BACKGROUND: Bioabsorbable steroid-releasing implants (mometasone furoate, 370 µg) are effective for improving postsurgical outcomes in the frontal sinus ostia (FSO). In this study we evaluated the effect of these implants on frontal outcomes in various patient subgroups with chronic rhinosinusitis (CRS) using pooled data from 2 randomized, controlled trials (RCTs). METHODS: A total of 160 subjects were enrolled in 2 RCTs. After surgery, subjects were randomized to receive an implant in 1 FSO with the contralateral side as control. Data through day 90 from the 2 studies were pooled and subgroup analyses were performed. RESULTS: At day 30, relative to controls, steroid-releasing implants significantly reduced the need for postoperative interventions by 46.8% (95% confidence interval [CI], -60.7 to -27.9), for surgical interventions by 51.2% (95% CI, -68.2 to -25.2), and for oral steroid interventions by 37.2% (95% CI, -54.6 to -13.1) in the pooled data set. At day 90, statistically significant reductions (p < 0.05) in the need for postoperative interventions (relative reduction [RR], 30.2%), restenosis/occlusion rate (RR, 31.7%), and inflammation score (absolute difference, -6.0), and increase in estimated FSO diameter (absolute difference, 1 mm), favoring the treated side, were observed. Subgroup analyses of the pooled data showed statistically significant improvements (p < 0.05) at day 90 in restenosis/occlusion rate, and estimated FSO diameter, favoring the treated side across subgroups, with no statistically significant subgroup-by-treatment interactions. CONCLUSION: Bioabsorbable steroid-releasing sinus implants improve outcomes of frontal sinus surgery through 90 days, irrespective of asthma status, previous endoscopic sinus surgery, extent of surgery, extent of polyps, or Lund-Mackay computed tomography stage in the FSO.

A phase 3 trial of mometasone furoate sinus implants for chronic sinusitis with recurrent nasal polyps.

BACKGROUND: Topical intranasal corticosteroid sprays (INCSs) are standard treatment for nasal polyps (NPs), but their efficacy is reduced by poor patient compliance and impaired access of drug to the sinus mucosa. A corticosteroid-eluting sinus implant was designed to address these limitations in patients with recurrent polyposis after sinus surgery by delivering 1350 µg of mometasone furoate (MF) directly to the ethmoid sinus mucosa over approximately 90 days. METHODS: A randomized, sham-controlled, double-blind trial was undertaken in 300 adults with refractory chronic rhinosinusitis with NPs (CRSwNP), who were candidates for repeat surgery. Eligible patients were randomized (2:1) and underwent in-office bilateral placement of 2 implants or a sham procedure. All patients used the MF INCS 200 µg once daily. Co-primary efficacy endpoints were the change from baseline in nasal obstruction/congestion score and bilateral polyp grade, as determined by an independent panel based on centralized, blinded videoendoscopy review. RESULTS: Patients treated with implants experienced significant reductions in both nasal obstruction/congestion score (p = 0.0074) and bilateral polyp grade (p = 0.0073) compared to controls. At day 90, implants were also associated with significant reductions in 4 of 5 prespecified secondary endpoints compared to control: proportion of patients still indicated for repeat sinus surgery (p = 0.0004), percent ethmoid sinus obstruction (p = 0.0007), nasal obstruction/congestion (p = 0.0248), and decreased sense of smell (p = 0.0470), but not facial pain/pressure (p = 0.9130). One patient experienced an implant-related serious adverse event (epistaxis). CONCLUSION: Significant improvements over a range of subjective and objective endpoints, including a reduction in the need for sinus surgery by 61%, suggest that MF sinus implants may play an important role in management of recurrent NP.

Safety and Effectiveness of a Bioabsorbable Steroid-Releasing Implant for the Paranasal Sinus Ostia: A Randomized Clinical Trial.

Importance: Suboptimal outcomes of endoscopic sinus surgery (ESS) are often associated with restenosis and inflammation of frontal sinus ostia. Steroid-releasing sinus implants have been shown to maintain sinus patency by minimizing inflammation and scar tissue formation. An hourglass-shaped, bioabsorbable, steroid-releasing implant was developed to provide mechanical support and optimize drug delivery to paranasal sinus ostia. Objective: To assess the safety and efficacy of the hourglass-shaped, bioabsorbable, steroid-releasing sinus implant in improving postoperative outcomes when placed in the frontal sinus ostia (FSO) following ESS in patients with chronic rhinosinusitis (CRS). Design, Setting, and Participants: In a prospective, multicenter, randomized clinical trial using an intrapatient control design (ESS followed by implant placement within 1 FSO vs ESS alone on the contralateral side) 80 adult patients, with a mean (SD) age of 49.5 (13.4) years and consisting of 53 (66%) men and 27 (34%) women, were enrolled and underwent bilateral frontal sinusotomies with 1 frontal sinus randomized to receive a steroid-releasing implant. The study was carried out in 12 US centers between July 2015 and March 2016. Interventions: A bioabsorbable steroid-releasing implant with hourglass shape containing 370 µg of mometasone furoate. All patients received standardized postoperative care. Main Outcomes and Measures: The need for postoperative interventions, medical and surgical, in the FSO at day 30, as determined based on review of video endoscopic findings by an independent blinded surgeon. Also, endoscopic grading by the independent reviewer and clinical investigators at day 30 and day 90 and computed tomographic scan at day 90. Results: The mean (SD) age of patients was 49.5 (13.4) years, 53 (66%) were men. Implants were successfully placed in all 80 randomized treatment sinuses. At day 30, steroid-releasing implants significantly reduced the need for postoperative interventions to 11.5% compared with 32.8% by surgery alone (mean difference, -21.3%; 95% CI, -35.1% to -7.6%), as assessed by the independent reviewer. Real-time endoscopic assessment by clinical investigators at day 30 demonstrated significant reduction in need for postoperative intervention (mean difference, -17.3%; 95% CI, -27.9% to -6.7%), significant reduction in inflammation score (mean difference, -12.3 mm; 95% CI, -18.3 to -6.4 mm), and significant reduction in rate of frontal restenosis or occlusion (mean difference, -22.7%; 95% CI, -33.5% to -11.9%) on treated compared with control sides. The results favoring the treatment sides were sustained through day 90: reduced need for postoperative interventions (mean difference, -11.7%; 95% CI, -21.0% to -2.4%) and reduction in restenosis and/or occlusion of the frontal ostium (mean difference, -17.4%; 95% CI, -28.6% to -6.1%). No implant-related adverse events were observed. Conclusions and Relevance: The hourglass-shaped steroid-releasing sinus implant was safe and more effective in maintaining FSO patency and improving surgical outcomes compared with surgery alone in the setting where no other immediate postoperative corticosteroids were administered. Trial Registration: ClinicalTrials.gov identifier: NCT02266810.

RESOLVE: bioabsorbable steroid-eluting sinus implants for in-office treatment of recurrent sinonasal polyposis after sinus surgery: 6-month outcomes from a randomized, controlled, blinded study.

BACKGROUND: Patients with recurrent sinonasal polyposis after endoscopic sinus surgery (ESS) have limited treatment options. Safety and efficacy were previously reported for a bioabsorbable sinus implant that elutes mometasone furoate for 3 months. Here we summarize longer-term outcomes. METHODS: A randomized, controlled, blinded study with 100 chronic rhinosinusitis with nasal polyps (CRSwNP) patients who failed medical treatment and were considered candidates for revision ESS. Treated patients (n = 57) underwent in-office implant placement. Control patients (n = 43) underwent a sham procedure. Endoscopic grading at 3 months by clinicians was corroborated by an independent review of randomized videoendoscopies by a panel of 3 sinus surgeons. Six-month follow-up included endoscopic grading and patient-reported outcomes. RESULTS: At 6 months, treated patients experienced significant improvement in Nasal Obstruction Symptom Evaluation (NOSE) score (p = 0.021) and >2-fold improvement in mean nasal obstruction/congestion score (-1.06 ± 1.4 vs -0.44 ± 1.4; p = 0.124). Endoscopically, treated patients experienced significant reduction in ethmoid sinus obstruction (p < 0.001) and bilateral polyp grade (p = 0.018) compared to controls. Panel review confirmed a significant reduction in ethmoid sinus obstruction (p = 0.010) and 2-fold improvement in bilateral polyp grade (p = 0.099), which reached statistical significance (p = 0.049) in a subset of 67 patients with baseline polyp burden ≥2 bilaterally. At 6 months, control patients were at 3.6 times higher risk of remaining indicated for ESS than treated patients. CONCLUSION: The symptomatic and endoscopic improvements observed confirm the efficacy of the steroid-eluting implant for in-office treatment of CRSwNP after ESS. These longer-term 6-month study results demonstrate that the steroid-eluting implant represents a durable, safe, and effective treatment strategy for this patient population.

Effect of steroid-releasing sinus implants on postoperative medical and surgical interventions: an efficacy meta-analysis.

BACKGROUND: Endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) can be compromised by postoperative inflammation, polyposis, and adhesions, often requiring subsequent interventions. A bioabsorbable, steroid-releasing sinus implant has been studied in 2 prospective, randomized clinical trials for its ability to preserve sinus patency and reduce medical and surgical interventions after ESS in patients with CRS. The objective of this study was to perform a meta-analysis of the efficacy results from the 2 trials. METHODS: The 2 prospective, randomized, double-blinded, multicenter trials enrolled a total of 143 patients utilizing an intrapatient control design. Postoperative day 30 videos were obtained for each patient, randomly ordered, and presented to an independent panel of 3 otolaryngologists for grading of efficacy endpoints. The need for postoperative interventions, formation of polyposis, and adhesions were assessed. Results from the 2 studies were then pooled. RESULTS: Implants were successfully placed in all 286 ethmoid sinuses. According to the grading done by the panel, drug-releasing implants reduced postoperative interventions by 35% (p = 0.0008), lysis of adhesions by 51% (p = 0.0016), and oral steroid need by 40% (p = 0.0023), compared to controls. The relative reduction in frank polyposis was 46% (p < 0.0001). CONCLUSION: Early postoperative healing is a predictor of longer-term success after sinus surgery. Evaluation of postoperative outcomes by a blinded independent panel demonstrates that steroid-releasing implants that provide a sustained release of corticosteroid improve surgical outcomes by reducing frank polyp formation, sinus adhesions, and middle turbinate lateralization. Steroid-releasing implants reduce the need for surgical intervention, and the need for oral steroid treatment.

Advance II: a prospective, randomized study assessing safety and efficacy of bioabsorbable steroid-releasing sinus implants.

OBJECTIVE: Endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) may be compromised by postoperative inflammation, polyposis, and adhesions, often requiring subsequent intervention. To address this issue, the authors investigated the safety and effectiveness of controlled delivery of mometasone furoate to the sinus mucosa via bioabsorbable implants deployed at the time of ESS. STUDY DESIGN: Prospective, multicenter, randomized, controlled, double-blind trial using an intrapatient control design. SETTING: Otolaryngology-head and neck surgery centers; both academic and private practices. SUBJECTS AND METHODS: The study enrolled 105 patients with CRS undergoing bilateral ethmoidectomy to compare the effect of drug-releasing to non-drug-releasing implants using an intrapatient control design. Postoperative interventions, polyposis, and adhesions were assessed postoperatively. Efficacy was determined through independent analysis of randomized video-endoscopies by 3 blinded sinus surgeons. Safety assessments included ocular examinations. RESULTS: Implants were successfully deployed in all 210 ethmoid sinuses. Compared with control sinuses with non-drug-releasing implants, the drug-releasing implant provided a 29.0% relative reduction in postoperative interventions (P = .028) and a 52% (P = .005) decrease in lysis of adhesions. The relative reduction in frank polyposis was 44.9% (P = .002). Similar reductions were observed in real-time grading performed by the clinical investigators. No clinically significant changes from baseline in intraocular pressure or cataracts were observed. CONCLUSION: This study provides a high level of evidence that use of steroid-releasing implants that apply a sustained release of corticosteroid improves surgical outcomes by reducing synechiae formation, polyposis, and the need for postoperative interventions, with no observable ocular safety risk.

Safety and efficacy of a novel bioabsorbable, steroid-eluting sinus stent.

BACKGROUND: Inflammation/polyp recurrence, adhesions, and middle turbinate lateralization are causes of suboptimal outcomes following sinus surgery and lead to increased rates of revision. A bioabsorbable, drug-eluting stent was evaluated for its ability to preserve sinus patency by providing controlled steroid delivery to the sinus mucosa. The study objective was to assess safety and efficacy of a steroid-eluting sinus stent when used following functional endoscopic sinus surgery (FESS) in patients with chronic rhinosinusitis (CRS). METHODS: Prospective, multicenter, randomized, double-blind clinical trial, enrolling 43 patients in 2 groups. One group (n = 38) used an intrapatient control design comparing drug-eluting to non-drug-eluting stents. The other group (n = 5) received bilateral drug-eluting stents to assess systemic safety. Endoscopic follow-up was performed for 60 days. Efficacy endpoints included assessment of inflammation, polyp formation, adhesions, and middle turbinate position. RESULTS: Stents were successfully deployed in all 86 sinuses. Compared to the control stent, the drug-eluting stent provided statistically significant reduction in inflammation at days 21 to 45 (p < 0.003), frequency of polyp formation (p = 0.0391), and frequency of significant adhesion (p = 0.0313). Reduced frequency of middle turbinate lateralization was also apparent though not statistically significant. No device-related adverse events occurred. Eluted steroid was unquantifiable systemically and there was no evidence of adrenal cortical suppression. CONCLUSION: This study demonstrates the safety and efficacy of a novel bioabsorbable, steroid-eluting stent for use in CRS patients. The steroid-eluting stent is effective in improving wound healing by preserving sinus patency, reducing inflammation, and minimizing adhesions via controlled local steroid delivery without measurable systemic exposure.