Since its introduction in the United States in 1985, the

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1 435968OTOXXX / Marp le et alotolaryngology Head and Neck Surgery 2012 The Author(s) 2010 Reprints and permission: sagepub.com/journalspermissions.nav Original Research Sinonasal Disorders Advance II: A Prospective, Randomized Study Assessing Safety and Efficacy of Bioabsorbable Steroid-Releasing Sinus Implants Otolaryngology Head and Neck Surgery 146(6) American Academy of Otolaryngology Head and Neck Surgery Foundation 2012 Reprints and permission: sagepub.com/journalspermissions.nav DOI: / Bradley F. Marple, MD 1, Timothy L. Smith, MD, MPH 2, Joseph K. Han, MD 3, Andrew R. Gould, MD, FAAOA 4, Henry D. Jampel, MD, MHS 5, James W. Stambaugh 6, and Andrew S. Mugglin, PhD 7 Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Abstract 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 nondrug-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. Keywords corticosteroid, sinusitis, polyposis, inflammation, endoscopic sinus surgery (ESS), drug releasing, implant Received August 29, 2011; revised December 9, 2011; accepted December 23, Since its introduction in the United States in 1985, the role of endoscopic sinus surgery (ESS) as an adjunct to medical therapy in the treatment of chronic sinus disease has expanded significantly. 1 Advances in surgical instrumentation, increased understanding of microanatomy, and development of surgical techniques aimed at mucosal preservation have enhanced its safety and effectiveness. Many surgeons consider the postoperative treatment regimen to be as important as the surgery itself. 2 There is strong evidence that postoperative endoscopic examination of the sinonasal cavity provides prognostic information concerning the potential for future episodes of sinusitis and that patients whose cavities 1 University of Texas Southwestern Medical Center, Dallas, Texas, USA 2 Oregon Health Sciences University, Portland, Oregon, USA 3 Eastern Virginia Medical School, Norfolk, Virginia, USA 4 Advanced ENT and Allergy, Louisville, Kentucky, USA 5 Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 6 Intersect ENT, Palo Alto, California, USA 7 University of Minnesota School of Public Health, Minneapolis, Minnesota, USA This article was presented at the 2011 AAO-HNSF Annual Meeting & OTO EXPO; September ; San Francisco, California. Corresponding Author: Bradley F. Marple, MD, Professor and Vice Chairman, Department of Otolaryngology Head and Neck Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX Bradley.Marple@UTSouthwestern.edu

2 Marple et al 1005 became normal postoperatively are less likely to require revision. 3 Common causes of suboptimal postoperative results include recurrent inflammation, polyposis, adhesion/synechiae formation, middle turbinate (MT) lateralization, and stenosis of sinus ostia. 4 Postoperative interventions are aimed at minimizing these issues and include medical therapy and debridements to lyse adhesions. These interventions are time-consuming and can be the most uncomfortable aspect of a patient s recovery. Current medical therapies have significant limitations. Oral corticosteroids carry systemic risks, including aseptic necrosis of the femoral head, calcium demineralization, cataract formation, and mood changes. 5,6 The efficacy of topical steroid spray in this setting is limited by postoperative edema, discharge, crusting, and poor patient compliance. The concept of impregnating nasal implants with corticosteroids has the potential to mitigate these concerns. Côté and Wright 7 reported significant improvement in postoperative healing in sinus cavities receiving direct application of topical steroids. An acknowledged limitation to this approach was the likely variable consistency and duration of drug delivery. A recent study by Murr et al 8 described the safety and efficacy of a steroid-impregnated sinus implant that is selfexpanding, is bioabsorbable, and provides sustained steroid release by delivering drug directly to the sinus mucosa. The study showed significant reductions in inflammation, polyp formation, and adhesions. The subsequent ADVANCE study with this same implant demonstrated low rates of synechiae and polyp formation, as well as significant improvements in patient symptoms through 6 months. 9 The ADVANCE II study was designed to assess the efficacy of this implant in reducing postoperative medical and surgical interventions. Methods Implant Description The treatment arm of this study used the Propel sinus implant (Intersect ENT; Palo Alto, California), which contains 370 µg mometasone furoate, embedded in a polymer matrix that provides local, controlled release of the drug over 30 days. Once inserted, the implant self-expands in spring-like fashion, propping open the cavity and conforming to the variable sinus anatomy without obstruction. Two implant versions identical in structure and appearance were used: a non-drug-releasing control and the steroid-releasing implant (Figure 1). The drug-releasing implants were investigational at the time of enrollment. The Food and Drug Administration (FDA) approved Propel in August Both implants are composed of polylactide-co-glycolide, a biologically inert 10 bioabsorbable polymer used in many FDA-approved technologies. Study Design A prospective, multicenter, randomized, double-blind, controlled clinical trial was conducted in the United States in patients undergoing ESS for treatment of chronic rhinosinusitis (CRS) refractory to medical management. The study used an intrapatient control design to minimize variability and allow Figure 1. Endoscopic photographs from study patient: (A) drugreleasing implant in right ethmoid, day 0; (B) control in left ethmoid, day 0; (C) and (D) are same sinuses, day 30. Drug-releasing implant (C) is normal, with no intervention required. Oral steroids required on control implant side (D). for blinded assessment. Patients received a drug-releasing sinus implant on one randomized side and an identical nondrug-releasing control implant on the contralateral side. An independent panel of 3 sinus surgeons was established to grade the day 30 endoscopies for assessment of the efficacy end points. The panel was kept blinded to origin of the videos, clinical information, and treatment assignment. Participating study centers obtained institutional review board approval for the protocol, and patients provided written informed consent prior to study entry. The study population included adult patients with CRS, with or without nasal polyps, scheduled to undergo ESS with bilateral ethmoidectomy and in whom placement of the implant was both feasible and medically appropriate. Patients were required to have a diagnosis of CRS defined as inflammation of the mucosa of the nose and paranasal sinuses of at least 8 consecutive weeks duration. Presence of bilateral ethmoid disease and candidacy for ESS were confirmed by computed tomography (CT) scan with a minimum Lund-MacKay stage of 6. Concurrent septoplasty and surgical treatment of other paranasal sinuses were permitted. Patients were excluded for a known history of immune deficiency, insulin-dependent diabetes, allergy or intolerance to corticosteroids, oral steroid-dependent condition, clinical evidence of acute bacterial sinusitis, or clinical evidence of invasive fungal sinusitis. Ocular exclusionary criteria included history or diagnosis of glaucoma or ocular hypertension, closed angle, presence of cataracts grade +3 or higher, or presence of posterior subcapsular cataract. Sinus randomization was performed following completion of successful ESS, prior to opening either implant package.

3 1006 Otolaryngology Head and Neck Surgery 146(6) Figure 2. Representative endoscopic grading form. Polypoid tissue grading: 0 = none, 1 = small amount of polyps/polypoid edema in middle meatus (MM), 2 = multiple polyps in MM, and 3 = polyps extending beyond MM. Grades 2 represent frank polyposis. Adhesion grading: 0 = none; 1 = small, nonobstructing; 2 = obstructing, easily separated; 3 = dense/obstructing, separation difficult; 4 = severe/complete adhesion of the middle turbinate (MT) to the lateral wall. Grades 2 to 4 were defined as requiring surgical lysis; grades 3, 4 were also categorized as significant adhesions. Panel members and clinicians also indicated whether oral steroid intervention was warranted based on endoscopic findings in the ethmoid sinus and MM alone. Implants were placed bilaterally in the ethmoid sinuses. No other methods of turbinate medialization were permitted (eg, suture, bolgerization), and placement of packing materials within the implants was disallowed unless medically necessary. Patients were allowed to use saline sprays or irrigation during follow-up. A standardized concomitant medications regimen was used to avoid confounding the efficacy assessment. Prior to ESS, there was no restriction on the use of systemic or topical steroids. During the initial 30-day follow-up, no oral or topical steroid sprays were permitted. Orally inhaled corticosteroids for asthma control were permitted, provided they were not started or stopped during the follow-up period. A 14-day course of antibiotics was required beginning 1 day prior to surgery. If infection was suspected at any time during the study, treatment with antibiotics was allowed. Follow-up visits occurred at postoperative days 14, 30, 60, and 90. An immediate postoperative visit for removal of packing, septal stents, or debridement was permitted. Endoscopic examinations, grading, and video recording occurred at days 14 and 30. Debridement was permitted during these visits. Videos from day 30 were provided to the panel for review and grading. Day 60 and 90 visits were performed via telephone contact or clinic visit. Ocular examinations were performed at baseline and days 14, 30, and 90. Implant performance and efficacy end points were determined from endoscopic examination and grading. Investigators participated in a training session prior to enrollment and prior to sinus grading. Training materials included representative images of various pathology. The primary efficacy end point was the reduction in need for postoperative interventions at day 30, as determined by the panel. Postoperative interventions were a composite end point defined as either surgical intervention to separate an adhesion and/or oral steroid intervention to resolve recurrent ethmoid sinus inflammation. The primary efficacy hypothesis was that the drug-releasing sinus implant would reduce the need for postoperative interventions at day 30 compared with control sides. The day 30 time point was selected for the efficacy measurement as it represents the latter part of the second phase of wound healing, characterized by edematous swelling of the residual mucosal tissue 11 ; is beyond the acute phase of crusting and bleeding, which allows unobstructed visualization of the mucosal tissue; and is often a key decision point for commencement of postoperative interventions. The video-endoscopies obtained at day 30 were edited to remove patient identifying information and to separate left and right sinus footage into separate video files. The files were then randomly ordered and provided to the 3-member panel for grading on standardized forms. Grading was based on endoscopy alone; panelists were not given any other clinical information. Panel members graded adhesion severity on a 5-point scale described by Murr et al, 8 polyp formation, and whether oral steroids were warranted (Figure 2). The need for intervention or polyp presence was declared based on a simple majority: at least 2 of the 3 raters needed to agree. In cases of disagreement, regrading was performed. These same end points were judged by on-site clinical investigators. On-site investigators also graded MT position (Figure 2). Safety was assessed by monitoring for device-related adverse events. Ocular safety was characterized by measurement of intraocular pressure (IOP) at baseline and days 14, 30, and 90. Dilated slit-lamp examination of the crystalline lens was performed at baseline and day 90. Examinations were performed by ophthalmologists. The IOP measurements were obtained by Goldman applanation or Tonopen tonometry. Lens opacities were classified on a 5-point scale. The Lens Opacities Classification System, Version III (LOCS III) was modified for the purposes of the study to grade cataracts in a consistent manner across centers. 12 Sites were provided with a classification guide that included photographic examples of the various cataract stages to enhance rating consistency across centers. The primary safety end point was defined as the absence of clinically significant IOP elevation through day 90. A clinically significant elevation was defined as an increase of 10

4 Marple et al 1007 Figure 3. Disposition of study subjects. ENT, ear, nose, and throat; FESS, functional endoscopic sinus surgery. mm Hg persisting for 2 weeks on the sinus side adjacent to the drug-releasing implant but not on the control side. The primary safety hypothesis was that the proportion of patients experiencing a clinically significant IOP elevation would be demonstrably less than 10%. Statistics The study was powered to pass both the primary efficacy and safety objectives. The primary efficacy objective relies on observing patients requiring intervention on one sinus side and not the other. Assuming 15% of study subjects would meet this criterion and that 92% of such cases would favor the side with the drug-releasing implant, a sample size of 105 patients (allowing for 5 lost to follow-up) was determined to provide >90% power. The prespecified statistical test for the primary efficacy end point and other binary efficacy outcomes was the McNemar test for correlated proportions. An exact version of the test was used if the number of discordant pairs for a given outcome was <20. All P values are 2-sided, and any P value <.05 is considered statistically significant. The test for the primary safety objective was a 1-sided exact binomial test. All data were entered into a validated database, and all personnel involved with the study conduct and data acquisition were kept blinded to randomization assignments throughout. Role of the Funding Source As this was an FDA-regulated trial, the study sponsor (Intersect ENT) provided the study implants, administrative/ logistical support in coordinating the study, and resources to conduct data analyses. All coauthors made substantial contributions to the study design, acquisition of data, interpretation of data/results, drafting and critically reviewing the article for content, and approving the final publication. Results A total of 105 patients were enrolled in the United States between December 2009 and July Patients were recruited in 11 otolaryngology head and neck surgery centers by 31 surgeons representing both academic and private practices. There was no evidence of site-to-site differences in primary efficacy outcomes. One hundred two of the 105 patients (97.1%) completed the ear, nose, and throat (ENT) follow-up visits through 90 Table 1. Baseline Demographics and Clinical Information Male, No. (%) 60 (57.1) Age, mean (minimum, maximum), y 46.5 (18, 76) Most common symptoms, No. (%) Nasal obstruction/congestion 95 (90.5) Headache 68 (64.8) Facial pain/pressure 64 (61.0) Discolored nasal drainage 57 (54.3) Hyposmia/anosmia 53 (50.5) Current smokers, No. (%) 18 (17.1) Aspirin intolerance/allergy, No. (%) 3 (2.9) Asthma, No. (%) 29 (27.6) Prior sinus procedure, No. (%) 31 (29.5) Polyps present, No. (%) 62 (59.0) Computed tomography stage, mean (treatment 12.8 (6.4, 6.4) side mean, control side mean) Table 2. Procedural Information No. (%) Bilateral ethmoidectomy 105 (100) Sphenoidotomy 66 (62.9) Frontal sinusotomy 72 (68.6) Middle meatus antrostomy (created or revised) 99 (94.3) Middle turbinate reduction 4 (3.8) Concha bullosa reduction 11 (10.5) Submucosal resection 11 (10.5) Septoplasty 59 (56.2) days. One hundred three of the 105 patients (98%) completed the ocular follow-up visits through 90 days (Figure 3). Patient baseline demographics and surgical details are provided in Tables 1 and 2, respectively. In the population, 29.5% had undergone 1 or more prior sinus procedures, and 59% presented with polyps at baseline. Fifteen patients from 8 study centers received oral steroids prior to surgery. Implants were successfully deployed in all 210 sinuses, and no packing was placed inside the ethmoid sinuses in any patient. Three patients received hemostatic agents prior to implant placement. All patients used saline sprays and/or irrigations during follow-up.

5 1008 Otolaryngology Head and Neck Surgery 146(6) Table 3. Principal Efficacy Results at Day 30 Treatment Sides, n = 105 Control Sides, n = 105 Relative Reduction, a %/P Value Postoperative intervention Evaluable b No. (%) No. (%) As determined by panel judgment (33.3) 45 (46.9) 29.0/.028 As determined by clinical investigators (21.9) 33 (31.4) 30.3/.068 Frank polyposis As determined by panel judgment (18.8) 29 (34.1) 44.9/.002 As determined by clinical investigators (3.8) 8 (7.7) 50.6/.344 Additional efficacy measures Middle turbinate lateralization (1.9) 7 (6.7) 71.6/.125 Significant adhesion c (4.8) 13 (12.5) 61.6/.039 a Relative reduction calculated as (Tx Rate Ctrl Rate)/(Ctrl Rate). b All patients returned for the day 30 visit and had their endoscopy recorded for grading by an independent panel; however, data were considered missing if the panel could not grade a video because of suboptimal video quality or inadequate imaging of the relevant anatomy. For the planned statistical tests, evaluable subjects were those with gradable sinuses on both sides if a side could not be graded, the subject was not included in the analysis. c Significant adhesion includes adhesions graded as dense or severe. Figure 4. Frequency of postoperative interventions by treatment group at day 30, as judged by the independent panel and in real time by on-site clinical investigators. Postoperative intervention is a composite of either surgical adhesion intervention and/or oral steroid intervention. Arrows with percentages indicate relative reductions. The rate of postoperative intervention by panel judgment was 46.9% on control sides compared with 33.3% on treatment sides (P =.028), a 29.0% relative reduction (Table 3 and Figure 4). Nine patients (8.6%) could not be included in the analysis because the video-endoscopy for either one or both sides was unable to be graded by the panel because of inadequate imaging of the relevant anatomy or suboptimal video quality. A prespecified imputation was performed for missing data by inserting ratings from clinical investigators into missing panel ratings, and the result remained significant (P =.023). The reduction in postoperative interventions was driven largely by the reduction in lysis of adhesions. The rate of adhesion lysis was reduced by 52.0% (P =.005), and need for oral steroids was reduced by 29% (P =.088). According to clinical investigators judgments, the rate of postoperative intervention was 31.4% on control sides compared with 21.9% on treatment sides (P =.068), a 30.3% relative reduction Figure 5. Frequency of frank polyposis by treatment group at day 30 as judged by the independent panel and real time by on-site clinical investigators. Arrows with percentages indicate relative reductions. (Table 3 and Figure 4). The relative reductions in adhesion lysis and oral steroid need were similar to the panel s findings: adhesion lysis was reduced by 43.0% (P =.033), and need for oral steroids was reduced by 25% (P =.388). The rate of frank polyposis by panel judgment was 34.1% on control sides compared with 18.8% on treatment sides (P =.002), a 44.9% relative reduction (Table 3 and Figure 5). With the imputation performed for missing data previously described, the result remained significant (P =.004). A significant correlation between frank polyposis and the need for oral steroids was observed (P <.0001 by χ 2 test). According to clinical investigators judgments, the rate of frank polyposis was 7.7% on control sides compared with 3.8% on treatment sides (P =.344), a 50.6% relative reduction. Middle turbinate lateralization occurred in 6.7% of control sides compared with 1.9% of treatment sides (P =.125). Significant adhesions (eg, scored as dense or severe) occurred in 12.5% of control sides compared with 4.8% of treatment sides (P =.039; Table 3 and Figure 6).

6 Marple et al 1009 Figure 6. Rates of significant adhesion formation and middle turbinate (MT) lateralization by treatment group at day 30 as determined in real time by on-site clinical investigators. Arrows with percentages indicate relative reductions. Figure 7. Changes from baseline in intraocular pressure by treatment side and time. Box and whisker plot. The primary safety hypothesis was met (P <.0001) as there were no clinically significant IOP increases per the prespecified definition. There were no clinically significant changes from baseline in lens opacities. Figure 7 provides the distribution of changes from baseline in IOP by treatment and time. One patient with a family history of glaucoma entered the study with moderately elevated IOP (pressures of 20 and 19 mm Hg) and later experienced a +12-mm Hg increase in 1 eye (adjacent to treated sinus) at day 90 that the ophthalmologist believed to be secondary to an acute exacerbation of sinusitis that was treated with topical steroids, oral steroids, and antibiotics. Pressures returned to baseline within 1 week after treatment with a pressure-lowering medication. Two adverse events were considered to be related to the implant. One patient required adhesion lysis bilaterally at day 14, with concurrent implant removal, due to crusting, granulation, and scarring of the MT that had begun at an earlier 1-week visit. The patient was treated with nasal irrigation, debridement, and prednisone taper, and the event resolved without sequelae. In a second patient, a control implant was removed 1 week postoperatively, and at 2 weeks, the endoscopic examination revealed frank pus in the contralateral sinus. A positive culture was obtained, and the patient was treated with a prednisone taper and amoxicillin. A relationship between the event and the study implant could not be ruled out. The event resolved without sequelae. Discussion Continual postoperative application of topical corticosteroids applied via a drug-releasing implant deployed at the time of surgery was studied to assess the effectiveness of this therapy in maintaining patency of the ethmoid sinus by reducing the frequency of postoperative interventions. This study is the first of its kind to assess efficacy of a drug-releasing sinus implant across multiple centers and surgeons, using an independent blinded panel of surgeons to assess efficacy outcomes, and the results are compelling. The reduction in the frequency of postoperative interventions and the need for adhesion lysis were both statistically significant and were corroborated by results from the real-time grading, illustrating the benefit of local, sustained-release corticosteroid delivery in maintaining sinus patency. It is noteworthy that no topical or oral steroids were permitted in the postoperative study period of 30 days and that 59% of the patients had presented with nasal polyposis at study entry. Several analyses related to the frequency of polypoid tissue formation were included to provide further insight into the benefit of sustained topical steroid release. There was a high degree of consistency between the results in these measures determined by the independent panel and the results from realtime grading by the on-site clinical investigators. By panel judgment, there was a highly significant correlation between the presence of frank polyposis and the need for oral steroid intervention (P <.0001). Relative reductions favoring the drug-coated implant were 45% (P =.002) and 51% (P =.344) for panel and real-time grading, respectively. These data provide further evidence of the benefit of sustained steroid release. The efficacy of the drug-releasing implant was determined in comparison to an identical control implant that provides similar spacing capability as traditional packing materials by propping open the sinus. 8 No intranasal or oral steroids were allowed in the first 30 days postoperatively. This was a necessary limitation of the study as it provided for completely blinded endoscopic grading and allowed for clear isolation of the benefit of sustained-release steroid therapy over the product s mechanical spacing function. Future studies may address the role of the implant in combination with other postoperative care regimens. Topical steroids are known to enhance early mucosalization, reduce edema, and reduce granulation tissue and fibrin deposition after sinus surgery. 11,13,14 The sustained release of steroid via the Propel implant led to a reduction in the need for medical and surgical intervention by reducing postoperative edema/inflammation and scarring. It also reduced postoperative issues such as MT lateralization and adhesions, which are frequently addressed by mechanical

7 1010 Otolaryngology Head and Neck Surgery 146(6) means. The feasibility of postoperative debridement in and around the implant was observed by clinical investigators. Outflow from the other sinuses appears to be maintained, and there was no difficulty debriding around the implant despite the fact that maxillary (94.3% of patients), sphenoid (62.9%), and frontal sinuses (68.6%) were surgically treated. Although involvement of an independent panel was scientifically rigorous and reduced the potential for rating bias, the approach required intervention decisions by panel members to be made without consideration of other patient factors available to the clinical investigators. We anticipated that the rates of intervention determined by the panel might be higher than those made in real time, where these other patient factors are taken into account. The efficacy results determined by investigators provide additional evidence of the efficacy of the implant, and it is encouraging that the same trends were observed across all efficacy end points by real-time grading compared with panel grading. From a safety standpoint, there were no clinically significant changes from baseline in lens opacities or IOP. These results are consistent with the findings in the previous ADVANCE trial. 9 Conclusion Continual postoperative application of topical corticosteroids applied via a drug-eluting stent deployed at surgery was studied to assess its impact on ESS outcomes. 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. Acknowledgments We acknowledge Neil Bhattacharyya, MD, for his role in the study design, participation on the independent panel, and data analysis, and Karen Fong, MD, for her role on the independent panel. In addition, we thank the following research staff at the study centers for their time and contributions to this research study: Steven K. Miller, MD (investigator) and Holly Featherstone, CCRP, of Intermountain Ear, Nose and Throat Specialists, Salt Lake City, Utah; Marti Gardner, MSN, and Gwen Pierce, RN, of Advanced ENT and Allergy, Louisville, Kentucky; J. Lewis Romett, MD (investigator), and Sharon Woodworth, RN, of Colorado ENT & Allergy, Colorado Springs, Colorado; Brent Lanier, MD (investigator), and JoAnn LoForti, RN, of Central California ENT Medical Group, Fresno, California; Pamela Kennedy of Eastern Virginia Medical School, Norfolk, Virginia; John McFarlane Sr, MD (investigator), Tammi Schreiner, LVN, and Damon Suhler of Austin Ear, Nose and Throat Clinic, Austin, Texas; Trevor I. Goldberg, MD (investigator), and Danielle Brooks, CCRP, of Charlotte Eye, Ear, Nose and Throat Associates, Charlotte, North Carolina; Rakesh K. Chandra, MD (investigator), and Donna Harakal, RN, of Northwestern University, Chicago, Illinois; Martin J. Citardi, MD (investigator), and Faramarz Ashoori of the University of Texas Medical Center, Houston, Texas; Barbara Staves of the University of Texas Southwestern Medical Center, Dallas, Texas; and Joseph Raviv, MD (investigator), and Michelle Catalano of NorthShore University Health System, Evanston, Illinois. Author Contributions Bradley F. Marple, study design, endoscopic grading methods, acquisition of data, analysis/interpretation of data, drafting and critically reviewing manuscript content, approval of final version to be published; Timothy L. Smith, study design, endoscopic grading methods, acquisition of data, interpretation of data, critically reviewing manuscript content, approval of final version to be published; Joseph K. Han, study design, acquisition of data, interpretation of data, critically reviewing manuscript content, approval of final version to be published; Andrew R. Gould, study design, endoscopic grading methods, acquisition of data, interpretation of data, critically reviewing manuscript content, approval of final version to be published; Henry D. Jampel, study design, analysis and interpretation of data, critically reviewing manuscript content, approval of final version to be published; James W. Stambaugh, study design, endoscopic grading methods, acquisition and analysis of data, critically reviewing content, approval of final version to be published; Andrew S. Mugglin, study design, analysis of data, interpretation of data, critically reviewing manuscript content, approval of final version to be published. Disclosures Competing interests: Bradley F. Marple is a consultant for Alcon, Teva, and Sunovion. Timothy L. Smith is a consultant for Intersect ENT and Entrigue, Inc and a recipient of grant funding. Henry D. Jampel is a consultant for Intersect ENT. James W. Stambaugh is an Intersect ENT employee and vice president of clinical affairs. Andrew S. Mugglin (statistician) is a consultant for Intersect ENT. Sponsorships: Intersect ENT (Palo Alto, California). The study was an FDA trial and therefore required that the sponsor provide the study implants, funding for the investigation, administrative/logistical support in coordinating the study across the multiple study sites, and resources to conduct data analysis. Funding source: None. References 1. Luong A, Marple BF. Sinus surgery: indications and techniques. Clin Rev Allergy Immunol. 2006;30: Bugten V, Norgard S, Steinsvag S. The effects of debridement after endoscopic sinus surgery. Laryngoscope. 2006;116: Kennedy DW, Wright ED, Goldberg AN. Objective and subjective outcomes in surgery for chronic sinusitis. Laryngoscope. 2000;110: Otto KJ, DelGaudio JM. Operative findings in the frontal recess at time of revision surgery. Am J Otolaryngol. 2010;31: Murr AH, Goldberg AN, Vesper S. 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