Devices for Post-Operative Use Following Endoscopic Sinus Surgery

Number: 0840

Policy

Aetna considers the use of the following sinus devices (not an all-inclusive list) for maintaining sinus ostial patency following endoscopic sinus surgery experimental and investigational because their effectiveness has not been established:

• Propel sinus implant
• Relieva Stratus MicroFlow spacer
• Sinu-Foam spacer

Background

Chronic rhino-sinusitis (CRS) is defined as an inflammatory condition involving the para-nasal sinuses and linings of the nasal passages that lasts 12 weeks or longer, despite attempts at medical management. It is one of the most frequently diagnosed chronic medical conditions, affect patients of all ages and gender.  Treatments of CRS include saline washes and sprays, topical and systemic glucocorticoids, antibiotics, anti-leukotriene agents, as well as anti-fungals.  Surgery should be the last resort in most cases of CRS.  Endoscopic sinus surgery (ESS) is the most commonly used surgical intervention to treat medically unresponsive CRS.  It is intended to restore physiologic sinus ventilation and drainage (Hamilos, 2012).  While ESS has become a well-established strategy for the treatment of CRS that is refractory to medical treatment, it is associated with various complications.  The incidence of major complications of ESS was estimated to be 1 to 3 %, with cerebrospinal fluid leak being the most common; and the incidence of minor complications was approximately 7.0 %, with middle meatal (MM) synechiae being the most common (May et al, 1994; Ramakrishnan et al, 2012).  Implantable sinus stents/spacers have been used following ESS to maintain patency of the sinuses and deliver local steroids. Self-dissolving sinus stents (eg, mometasone furoate sinus implant), deliver a sustained, localized, controlled release of medication (eg, corticosteroid). The device is implanted during sinus surgery where it expands to prop open the sinus, support the bony structures inside the nose and is purported to prevent scar formation. 

Steroid-Eluting Sinus Implants/Stents (e.g., Propel Sinus Implant)

The Propel sinus implant is a steroid-releasing sinus implant that is inserted into the ethmoid sinus. It is indicated for maintaining sinus patency after ESS in patients 18 years of age and older.  This steroid-releasing implant is comprised of a synthetic bio-absorbable co-polymer and is self-expanding, which allows it to conform to the highly variable contours and size of the sinus anatomy. The Propel sinus implant is inserted into the ethmoid sinus cavity by a physician under endoscopic visualization.  Upon insertion, the implant expands radially to conform to the sinus cavity.  The delivery system is then removed and discarded.  Once Propel is in place, mometasome furoate is released over a 30-day period.  Dosages for Propel are measured in terms of the number of implants inserted in a patient's sinus cavities.  Each steroid-releasing implant contains 370 ug of mometasome furoate.

In a prospective, multi-center, single-cohort trial (Advance Trial), Forwith et al (2011) evaluated the safety and effectiveness of a bio-absorbable, steroid-eluting implant (the Propel device) used following ESS in patients with CRS (n = 50). The study allowed bilateral or unilateral steroid-eluting implant placement.  Oral and topical steroids were withheld for 60 days post-operatively.  Endoscopic follow-up was performed to 60 days.  Patient-reported outcomes (22-item Sino-Nasal Outcome Test [SNOT-22 Questionnaire], Rhinosinusitis Disability Index) were collected to 6 months.  Effectiveness was assessed by grading inflammation, polyp formation, adhesions, and middle turbinate position.  Safety assessment included ocular examinations at baseline and 30 days.  Implants were successfully placed in all 90 sinuses.  Mean inflammation scores were minimal at all time-points.  At 1 month, the prevalence of polypoid edema was 10.0 %, significant adhesions 1.1 %, and middle turbinate lateralization 4.4 %.  Changes from baseline in patient-reported outcomes were statistically significant (p < 0.0001).  No clinically significant changes from baseline in intra-ocular pressure (IOP) occurred.  The authors concluded that this consecutive case-series study provided clinical evidence of the safety, effectiveness, and clinical utility of a bio-absorbable steroid-eluting implant for use in CRS patients.  The implant was associated with favorable rates of sinus patency.  At 1 month, minimal degrees of inflammation and adhesions were observed, suggesting a positive clinical impact of local steroid delivery without evidence of ocular risks.

In a prospective, multi-center, randomized, controlled, double-blind trial (Advance II Trial), Marple et al (2012) examined the safety and effectiveness of controlled delivery of mometasone furoate to the sinus mucosa via the Propel sinus implant deployed at the time of ESS. This study enrolled 105 patients with CRS undergoing bilateral ethmoidectomy to compare the effect of drug-releasing to non-drug-releasing implants using an intra-patient control design.  Post-operative interventions, polyposis, and adhesions were assessed post-operatively.  Effectiveness was determined through independent analysis of randomized video-endoscopies by 3 blinded sinus surgeons.  Safety assessments included ocular examinations.  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 post-operative interventions (p = 0.028) and a 52 % (p = 0.005) decrease in lysis of adhesions.  The relative reduction in frank polyposis was 44.9 % (p = 0.002).  Similar reductions were observed in real-time grading performed by the clinical investigators.  No clinically significant changes from baseline in IOP or cataracts were observed.  The authors concluded that this study provided evidence that use of the Propel sinus implant that applied a sustained release of corticosteroid improved surgical outcomes by reducing synechiae formation, polyposis, and the need for post-operative interventions, with no observable ocular safety risk.

While the results of the 2 Advance Trials were promising, they were limited to small, heterogeneous inpatient populations with short-term follow-up. Furthermore, the trials were performed in a setting where both sinuses had implants, one with steroid and the other without.  The 2 Trials discussed above did not compare the post-operative outcomes using this device with outcomes following standard ESS without an ostial implant but with topical steroid sprays, saline irrigation, debridement, and conventional post-operative packing.  The available evidence is insufficient to determine whether sinus spacers and stents improve outcomes when used post-operatively following ESS.  Further randomized controlled trials (RCTs) are needed to compare the Propel device to optimal post-operative care without the device to examine if it can improve post-operative outcomes for patients undergoing ESS.

In a Cochrane review, Huang and colleagues (2015) evaluated the safety and effectiveness of steroid-eluting sinus stent placement in CRS patients after functional ESS (FESS). Data sources included the Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 4); PubMed; Embase; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials.  The date of the search was May 14, 2015.  These researchers included all RCTs comparing steroid-eluting sinus stents with non-steroid-eluting sinus stents, nasal packing or no treatment in adult CRS patients undergoing FESS.  They used the standard methodological procedures expected by the Cochrane Collaboration.  These investigators identified no RCTs that met the inclusion criteria.  Among the 159 records retrieved using the authors’ search strategy, a total of 21 trials had the potential to be included given that they had tested sinus stents, spacers and packing materials for patients with CRS undergoing FESS.  However, these researchers excluded these trials from the review because they met some but not all of the inclusion criteria.  The authors were unable to provide evidence to establish whether steroid-eluting sinus stents have potential advantages and disadvantages for patients with CRS undergoing FESS.  Moreover, they stated that future, high-quality RCTs are needed to determine whether or not steroid-eluting sinus stents confer any beneficial effects, over those of surgery alone, when compared to non-steroid sinus stents.

In a systematic review, Rizan and Elhassan (2016) evaluated the safety and effectiveness of steroid-eluting bioabsorbable intranasal devices (SEBID). The secondary aim was to inform clinical recommendations and to introduce clinicians to this novel technology.  Medline, PubMed, Embase, and Cochrane Database were searched according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines.  Original articles assessing the effectiveness of SEBIDs inserted after ESS.  For each study, these researchers recorded the effectiveness end-points and safety outcomes.  A total of 7 studies met the inclusion criteria from 737 initial articles identified, including 5 prospective RCTs and 2 prospective single-cohort studies involving 394 sinuses within treatment arms.  Patients were followed-up for 2 to 6 months; 6 studies demonstrated SEBID effectiveness with statistical significance (p < 0.05).   Steroid-eluting bioabsorbable intranasal devices were effective in reducing adhesion formation, polyp formation, inflammation, Lund-Kennedy scores, and peri-operative sinus endoscopy scores.  The devices improved patient-reported outcomes and olfaction while reducing post-operative interventions.  They were not associated with adverse events and posed no ocular safety risk.  Complications in 3 SEBID applications were reported.  The authors concluded that there is limited data available on SEBIDS; further studies are needed to examine if they are safe and effective adjuncts post-ESS.  They stated that future studies are needed to optimize the dosing regimen, compare devices, and provide long-term outcomes.

An assessment by the National Institute for Health and Care Excellence (NICE, 2016) concluded: "Current evidence on the safety of corticosteroid-eluting bioabsorbable stent or spacer insertion during endoscopic sinus surgery to treat chronic rhinosinusitis raises no major safety concerns. The evidence on efficacy is limited; there is some evidence of improving sinus patency in the short term, but there is inadequate evidence on patient-reported outcomes and quality of life. Therefore, this procedure should only be used with special arrangements for clinical governance, consent, and audit or research. . . NICE encourages further research on corticosteroid-eluting bioabsorbable stent or spacer insertion during endoscopic sinus surgery and, specifically, controlled studies designed for between-patient (rather than within-patient) comparisons. Outcomes should include symptom scores, quality of life and the need for retreatment in the long term. All complications should be reported."

Matheny and colleagues (2014) evaluated the safety, feasibility, and outcomes of steroid-eluting bioabsorbable sinus implants placed in the office after achieving hemostasis.  A total of 20 patients with CRS underwent ESS including bilateral ethmoidectomy.  A steroid-eluting bioabsorbable implant was deployed into each ethmoid cavity in the office within 7 days after ESS.  Endoscopic appearance of the ethmoid cavities was evaluated at 1 week, 2 weeks, and 4 weeks post-operatively by the operating surgeon and an independent blinded evaluator.  Procedural tolerance was assessed at week 2 using a patient preference questionnaire.  The 20-item Sino-Nasal Outcome Test (SNOT-20) questionnaire was completed at baseline, week 2, and week 4.  In-office placement of steroid-eluting bioabsorbable implants was well-tolerated, with 90 % of patients very satisfied with the overall experience, and 80 % very satisfied with the recovery process.  At 1 month, there were no significant adhesions or frank polyposis, and middle turbinate lateralization was only 5 %.  Compared to baseline, ethmoid sinus inflammation was significantly reduced (p = 0.03), and the mean SNOT-20 score was significantly improved (p < 0.001).  The authors concluded that in-office placement of steroid-eluting bioabsorbable implants after achieving hemostasis was well-tolerated and might improve local drug diffusion and surgical outcomes.  This was a small study (n = 20) with short-term follow-up (4 weeks).

Pou and associates (2017) examined if the severity of pre-operative sino-nasal inflammation influences the post-operative changes in patient-reported quality of life (QOL) and endoscopic appearance following ESS with implant placement.  Consecutive adult patients undergoing ESS for CRS with ethmoidectomy and placement of a steroid-eluting implant over an 18-month period were prospectively included for study.  Pre-operative sinus computed tomography (CT) opacification was evaluated using the Lund-Mackay score (LMS); SNOT-22 scores and Lund-Kennedy endoscopic scores (LKES) for each patient were collected pre-operatively and at 3- and 6-month intervals post-operatively.  Serum eosinophilia (greater than 6.0 % on peripheral smear) and sinus tissue eosinophilia were recorded.  A total of 136 patients were included for analysis.  Of these, 36.7 % had polyposis, 15.4 % had serum eosinophilia and 64.0 % had tissue eosinophilia.  The mean (standard deviation) SNOT-22 score was 45.5 (19.4) pre-operatively, which improved post-operatively to 18.8 (14.1) at 3 months (p < 0.001) and 16.5 (14.0) at 6 months (p < 0.001).  Similar results were found when stratified by the presence of polyposis, serum eosinophilia, tissue eosinophilia or high-grade CT findings (LMS greater than 6).  Higher baseline LKES was observed for patients with eosinophilia or high-grade LMS, but these differences normalized at 6 months post-operatively.  The authors concluded that patient-reported QOL and endoscopic appearance showed improvement 6 months after placement of a steroid-eluting implant during ESS, irrespective of the presence of polyposis or eosinophilia.  Moreover, they stated that although the present study indicated that improvements occurred regardless of the severity of pre-operative inflammation, it remained unclear how these effects would compare to cases in which an implant was not utilized.  Future studies with controlled trials of patient-reported QOL following ESS with bioabsorbable steroid-eluting implants are needed, which may utilize post-operative objective markers of inflammation to supplement the effects on patient-reported QOL.  Investigation of the effect of simultaneous additional symptom scores or QOL measures may help elucidate the confounding potential of septoplasty and inferior turbinate reduction in conjunction with ESS.  Lastly, examination into specific items of the SNOT-22 score that are most affected by implant placement may result in better pre-operative counseling and patient selection.

Luong et al (2018) evaluated the safety and effectiveness of the hourglass-shaped, bioabsorbable, steroid-releasing sinus implant (370 ug mometasone furoate) in improving post-operative surgical outcomes when placed in the FSO following ESS in patients with CRS.  A total of 80 adult (mean (SD) age of 49.5 (13.4) years; 53 (66 %) men and 27 (34 %) women) CRS patients who underwent bilateral frontal sinusotomy were randomized to receive a steroid-releasing implant in one FSO, whereas the contralateral control side received no implant.  All patients received standard post-operative care.  Endoscopic evaluations recorded at 30-day post-ESS were graded real time by clinical investigators and by an independent, blinded sinus surgeon to assess the need for post-operative interventions in the FSO.  Also, endoscopic grading by the independent reviewer and clinical investigators at day 30 and day 90 and computed tomographic scan at day 90 were performed.  Implants were successfully placed in all 80 frontal sinuses, resulting in 100 % implant delivery success.  At 30-day post-ESS, steroid-releasing implants significantly reduced the need for post-operative interventions to 11.5 % compared with 32.8 % by surgery alone (mean difference [MD] -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 showed significant reduction in need for post-operative intervention (MD -17.3 % , 95 % CI: -27.9 % to -6.7 %), significant reduction in inflammation score (MD -12.3 mm, 95 % CI: -18.3 to -6.4), and significant reduction in rate of frontal re-stenosis or occlusion (MD -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 (MD -11.7 %, 95 % CI: -21.0 % to -2.4 %) and reduction in re-stenosis and/or occlusion of the frontal sinus (MD -17.4 %, 95 % CI: -28.6 5 to -6.1 %).  No implant-related adverse events were reported.  The authors concluded that the hourglass-shaped, bioabsorbable, steroid-releasing sinus implant was safe and effective in maintaining FSO patency and improving surgical outcomes compared with surgery alone in the setting where no other immediate post-operative corticosteroids were administered.

Relieva Stratus MicroFlow Spacer

The Stratus MicroFlow Spacer is designed to provide slow release of steroids into the sinuses over a 2-week period with the intention of maintaining sinus ostial patency. This device may be used in either the frontal or ethmoid sinuses.

Catalano et al (2011) evaluated the safety and short-term outcomes of a newly introduced drug-eluting ethmoid stent (the MicroFlow Spacer) in 23 patients with a total of 40 implanted ethmoid sinuses. Patients with medically refractory CRS were treated with patient-appropriate ESS, with the modification of treating the ethmoid sinuses with an ethmoid stent infused with triamcinolone, instead of conventional endoscopic ethmoidectomy.  Patients were then followed-up over 6 months.  Safety was determined by adverse events.  Outcomes were assessed by interval changes in SNOT-20 and Lund-MacKay CT scores.  Overall, the pre-operative SNOT-20 mean score was 2.18, versus post-operative score of 1.02, an improvement of 1.16 that was both statistically (p < 0.001) and clinically significant.  Ethmoid-specific and side-specific Lund-MacKay mean scores both also showed statistically significant improvements.  Pre-operative ethmoid-specific Lund-MacKay mean score was 1.93, versus post-operative score of 1.10, an improvement of 0.83 (p < 0.001).  Pre-operative side-specific Lund-MacKay mean score was 5.75, compared with post-operative score of 2.95, an improvement of 2.80 (p < 0.001).  There were no significant intra-operative or post-operative complications encountered.  The authors concluded that the MicroFlow spacer appeared safe and effective in treating chronic ethmoid sinus disease within the defined follow-up period.  They noted that the ability to deliver medication directly to diseased mucosa held wide-ranging potential.  The findings of this small study need to be validated by well-designed studies with long-term follow-up.

Taulu and associates (2015) stated that anatomical complexity presents the main challenge in the administration of topical corticosteroid therapy to the para-nasal sinus mucosa. This often led to suboptimal drug delivery due to low concentrations of the therapeutic agent to the intended target area.  The Relieva Stratus MicroFlow Spacer (Relieva Stratus) is a drug-eluting stent that is temporarily implanted into the ethmoid sinus.  The reservoir of the stent is filled with triamcinolone acetonide, which is then slowly released from the device into the ethmoid sinus mucosa.  The Relieva Stratus provides local and targeted delivery of the anti-inflammatory agent to the diseased mucosa.  This minimally invasive implant is an option when treating ethmoid sinusitis.  From January 2011 to November 2013, a total of 52 Relieva Stratus implantations into the ethmoidal cells were performed at the Department of Ear and Oral Diseases at Tampere University Hospital, Finland; C-arm fluoroscopy guidance was employed for 26 sinuses (13 patients) and optical image-guided surgery (IGS)-assisted insertions were performed on another 26 sinuses (13 patients).  The accuracy of fluoroscopic insertion was not optimal, but this method was accurate enough to prevent the violation of the skull base and lamina papyracea.  Image-guided surgery enabled the precise treatment of the diseased cells.  From a technical perspective, IGS-guided insertion was a faster, safer and more exact procedure that guaranteed the optimal positioning and effectiveness of the implant.  Moreover, IGS guidance did not entail the use of ionizing radiation.  The findings of this small study (n = 25) need to be validated by well-designed studies.

In May 2013, Acclarent voluntarily discontinued all sales of the Stratus device and withdrew all approved FDA clearances, making the devices no longer available for sale in the United States.

Businco and colleagues (2016) evaluated the safety and effectiveness of the steroid-eluting ethmoidal stent (SEES; the Relieva Stratus MicroFlow Spacer) in the management of allergic CRS in comparison with the traditional endoscopic ethmoidectomy (EE).  A total of 70 allergic patients who presented CRS were randomly divided into 2 groups and received respectively the SEES or EE.  The most significant observation coming from the comparative analysis of the results was the substantial equivalence of the treatment with the SEES compared with EE in the management of ethmoid CRS with the exception of a reduction of overall discomfort and nasal secretion and better functional results at rhinomanometry in the SEES group.  The authors concluded that in their experience, the SEES was effective in the treatment of allergic patients with ethmoidal CRS when conventional medical treatment had failed, or when wishing to avoid the classic EE; however, further long-term studies are needed to confirm the safety and stability, over time, of the results obtained.

Sinu-Foam Spacer

Sinu-Foam is an Food and Drug Administration (FDA)-approved mixture, which is commonly mixed with saline and gently placed in the ethmoid cavity following FESS.  A dexamethasone Sinu-Foam spacer has been studied to examine if it could promote wound healing of the nasal and sinus mucosa by reducing the inflammation associated with CRS.  However, its clinical utility remains a debate since it does not improve endoscopic outcomes in the early post-operative period following FESS.

In a randomized, double-blind, placebo-controlled trial, Rudmik et al (2012) evaluated a dexamethasone Sinu-Foam spacer following ESS for CRS without nasal polyposis (CRSsNP). Patients with CRSsNP (n = 36) were enrolled into a double-blind, placebo-controlled trial and randomized into either a treatment arm (dexamethasone Sinu-Foam mixture; n = 18) or placebo arm (Sinu-Foam alone; n = 18).  Therapeutic outcomes were evaluated at 1 week, 4 weeks, and 3 months using sino-nasal endoscopy and graded using the Lund-Kennedy scoring system.  Post-operative care included nasal saline irrigations and a short course of systemic steroids.  All patients completed the study follow-up period.  Both study arms experienced significant improvement in endoscopic grading over the study duration (p < 0.001).  There was no difference in average endoscopic scores between the treatment and placebo groups at 1 week, 4 weeks, and 3 months (all p > 0.489).  The authors concluded that the findings of this study demonstrated that an off-label drug-eluting MM spacer of dexamethasone and Sinu-Foam did not improve endoscopic outcomes in the early post-operative period following ESS when combined with post-operative saline irrigations and a short course of systemic steroids.

In summary, a variety of implants/spacers (e.g., the Propel sinus implant, the Relieva Stratus MicroFlow spacer, and the Sinu-Foam spacer) have been employed to maintain patency of the sinuses and deliver local steroids with varying success in the reported literature.  However, the available studies have significant heterogeneity in this outcome.  There remains a continued debate on whether these devices actually improve the health outcomes following ESS.

The above policy is based on the following references: