Chronic Rhinosinusitis

Chronic rhinosinusitis is an inflammatory sinus condition that has a prevalence between 1% and 5% in the U.S. population.^1,

Treatment

Endoscopic sinus surgery (ESS) is typically performed on patients with chronic rhinosinusitis unresponsive to conservative treatment. The surgery is associated with high rates of improvement in up to 90% of more appropriately selected patients. However, there are no high-quality randomized controlled trials comparing functional ESS with continued medical management or alternative treatment approaches. Because of the high success rates and minimally invasive approach, these procedures have rapidly increased in frequency, with an estimated 250,000 procedures performed annually in the United States.^2, They can be done either in the physician’s office under local anesthesia or in the hospital setting under general anesthesia.

ESS involves the removal of small pieces of bone, polyps, and débridement of tissue within sinus cavities. There are a number of variations on the specific approach, depending on the disorders being treated and the preferences of the treating surgeon. For all procedures, there is substantial postoperative inflammation and swelling, and postoperative care is therefore a crucial component of ESS.

There are a number of postoperative treatment regimens, and the optimal regimen is uncertain. Options include saline irrigation, nasal packs, topical steroids, systemic steroids, topical decongestants, oral antibiotics, and/or sinus cavity débridement. Several randomized controlled trials have evaluated treatment options, but not all strategies have been rigorously evaluated.^3,4,5,6, A 2011 systematic review has evaluated the evidence for these therapies.^2, Reviewers concluded that the evidence was not strong for any of these treatments but that some clinical trial evidence supported improvements in outcomes. The strongest evidence supported use of nasal saline irrigation, topical nasal steroid spray, and sinus cavity débridement.

Some form of sinus packing is generally performed postoperatively. Simple dressings moistened with saline can be inserted manually following surgery. Foam dressings are polysaccharide substances that form a gel when hydrated and can be used as nasal packs for a variety of indications.^7,Middle meatal spacers are splint-like devices that prop open the sinus cavities post-ESS, but are not designed for drug delivery. There is some randomized controlled trial evidence that middle meatal spacers may reduce the formation of synechiae following ESS, although the available studies have significant heterogeneity in this outcome.^8,

Implantable Sinus Stents

Implantable sinus stents are another option for postoperative management following ESS. These implants are intended to stabilize the sinus openings and the turbinates, reduce edema, and/or prevent obstruction by adhesions. They can also be infused with medication delivered topically over an extended period of time, and this local delivery of medications may be superior to topical application in the postoperative setting.

Regulatory Status

Intraoperative Steroid-Eluting Sinus Stents

In 2011, the PROPEL(R) system (Intersect ENT, Menlo Park, CA) was approved by the U.S. Food and Drug Administration (FDA) through the premarket approval process (P100044). This device is a self-expanding, bioabsorbable, steroid-eluting stent intended for use in the ethmoid sinus. It is placed via endoscopic guidance using a plunger included with the device. Steroids (mometasone furoate) are  released over an approximate duration of 30 days. The device dissolves over several weeks, and therefore does not require removal. In 2012, a smaller version of the PROPEL(R) device, the PROPEL(R) mini Sinus Implant, was approved for use in patients older than age 18 years following ethmoid sinus surgery. In 2017, the PROPEL Contour was approved through a PMA supplement. The PROPEL(R) Contour Sinus Implant is an adaptable implant that is designed to maximize drug delivery to the frontal and maxillary sinus.

Postoperative Steroid-Eluting Sinus Stents

SINUVA(TM) Sinus Implant (Intersect ENT, Inc., Menlo Park, CA) was initially approved in 1987. In 2017, the SINUVA(TM) Sinus Implant was approved with a new dose  (1350 μg mometasone furoate)  under a New Drug Application (NDA 209310). The corticosteroid  is released over 90 days and the bioabsorbable polymers soften over this time. The implant is removed at Day 90 or earlier using standard surgical instruments. The SINUVA™ Sinus Implant is indicated for the treatment of nasal polyps in adult patients who have had ethmoid sinus surgery. 

FDA product code: OWO

Related Policies

• Balloon Ostial Dilation as an Alternative to Endoscopic Sinus Surgery for Treatment of Chronic Rhinosinusitis (Policy #077 in the Surgery Section)

Foam dressings, such as Sinu-Foam™, are used as nasal packs for a variety of conditions, including nosebleeds, and have also been used after endoscopic sinus surgery (ESS). They are considered different types of nasal packing.

Middle meatal spacers are related but separate devices intended to maintain sinus patency post-endoscopic sinus surgery. They are splint-like devices inserted directly rather than under endoscopic guidance, and do not have the capability of delivering local medication.

[RATIONALE: This policy was created in 2012 and has been updated regularly with searches of the MEDLINE database. The most recent literature update was performed through December 4, 2018.

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to functionincluding benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

RCTs are important in the evaluation of sinus implants as an adjunct to endoscopic sinus surgery (ESS) to adequately compare implantable stents with alternative treatment regimens and to minimize the effects of confounders on outcomes. Case series and trials without control groups offer little in the way of relevant evidence, because improvement in symptoms is expected after ESS and because there are multiple clinical and treatment variables that may confound outcomes.

Steroid-Eluting Stents as an Adjunct to ESS

Clinical Context and Therapy Purpose

The purpose of a steroid-eluting sinus stent in patients who have chronic rhinosinusitis who have endoscopic sinus surgery is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: does the adjunctive use of a steroid-eluting sinus stent improve the net health outcome in patients who have endoscopic sinus surgery?

The following PICOTS were used to select literature to inform this review.

Patients

The relevant population(s) of interest are patients who have endoscopic sinus surgery for chronic rhinosinusitis.

Interventions

The therapy being considered is a bioabsorbable steroid-eluting sinus stent (eg, PROPEL Sinus Stent, PROPEL mini Sinus Stent, PROPEL Countour Sinus Stent) for post-operative care following ESS. 

Comparators

The most relevant comparison for sinus stents is unclear because there is no standardized optimal postoperative treatment regimen. Ideally, the “standard care” comparison group should include some form of packing, intranasal steroids, and irrigation. An important consideration in evaluating controlled trials is that the control arm may not be treated with optimal intensity, thereby leading to a bias in favor of the device. For example, a study design that compares a steroid-eluting stent with a non-steroid-eluting stent will primarily evaluate the efficacy of steroids when delivered by the device, but will not evaluate the efficacy of a stent itself. If the control group does not receive topical or oral steroids postoperatively, then this might constitute undertreatment in the control group and result in a bias favoring the treatment group. Another concern is comparison of the efficacy of a drug with the efficacy of a drug delivery system. For example, if a steroid-eluting spacer is compared with a control of saline irrigation alone, it will be difficult to separate the efficacy of the drug itself (steroids) from the drug delivery system (stent).

Outcomes

The Perioperative Sinus Endoscopy score sums the combined scores determined from middle turbinate position, middle meatal status, ethmoid cavity appearance, as well as secondary sinus blockage (frontal and sphenoid). Each category is scored from 0-2, with 0 being not present, 1 as partially present, and 2 being fully present. The highest total score is 16, with scores ranging from 18-20 when the frontal and sphenoid sinuses are also included. The higher the score, the worse the status of the nasal cavity.

Post-ESS synechiae formation, the Sino-Nasal Outcome Test (SNOT-22) Questionnaire and the Rhinosinusitis Disability Index may also be used to evaluate perioperative outcomes.

A beneficial outcome would be an improvement in symptoms.

A harmful outcome would be adverse events from the implantable stents.

Timing

The PROPEL series of sinus stents are bioabsorbable and elute steroids for 30 days. Therefore, outcomes should be assessed within 30 days.

Setting

The setting is treatment by an otolaryngologist in a surgical center.

Review of Evidence

The literature consists of randomized trials, single-arm case series, and systematic reviews of these studies. The following is a summary of the key findings to date.

Systematic Reviews

A 2015 Cochrane review addressed steroid-eluting sinus stents for improving chronic rhinosinusitis (CRS) symptoms in individuals undergoing ESS.^9, Study eligibility criteria were RCTs that compared the effects of steroid-eluting sinus stents with non-steroid-eluting sinus stents, nasal packing, or no treatment in adults with CRS who underwent ESS. After an initial search, 21 RCTs were identified, including the RCTs reported by Murr et al (2011)^10, and Marple et al (2012)^11,  (described above). None of the trials met authors’ inclusion criteria. Reviewers concluded that there was no evidence from high-quality RCTs to demonstrate the benefits of steroid-eluting stents.

Randomized Controlled Trials

RCTs are shown in Tables 1 and 2. There are 4 RCTs of the PROPEL, PROPEL mini, and PROPEL Contour steroid-eluting sinus stents, all sponsored by the device manufacturer (Intersect ENT).These trials used an intrapatient control design, with each patient receiving a drug-eluting stent on 1 side and a non-drug-eluting stent or medical treatment on the other via random assignment.

The two trials of PROPEL for the ethmoid sinus had similar designs.^10,11, Both compared an implant that is steroid-eluting with an identical non-steroid-eluting implant. Thus these trials tested the value of drug delivery via a stent, but did not test the value of a stent itself vs treatment without a stent. The primary efficacy outcome in Murr et al was degree of inflammation rated by the treating physician.^10, In Marple et al the primary outcome was reduction in the need for postoperative interventions at day 30 postprocedure.^11, A panel of 3 independent experts, blinded to treatment assignment and clinical information, viewed the endoscopic results and determined whether an intervention was indicated. The need for postoperative intervention by expert judgment was found in 33.3% of patients in the steroid-eluting arm and in 46.9% in the non-steroid-eluting arm (p=0.028). The reduction in interventions was primarily driven by a 52% reduction in lysis of adhesions (p=0.005). The primary safety hypothesis was met, because there were no cases of clinically significant increases in ocular pressure recorded over the 90-day period postprocedure.

The RCTs by Smith et al (2016) and Luong et al (2017), implanted either a PROPEL Mini Sinus Implant or a PROPEL Contour Sinus Implant in the frontal sinus with a control of surgery alone on the contralateral side.^12,13, The primary outcome was the need for post-operative intervention (eg, surgery or steroids) determined by an independent blinded physician. Both trials showed a reduction in the need for additional surgical intervention by approximately 22%, with no adverse effects of treatment. The number needed to treat was 4.7 to prevent 1 patient from undergoing postoperative intervention.^13, No stent-related adverse events were noted.

Table 1. Summary of Key RCT Characteristics

Study; Trial	Countries	Sites	Dates	Participants	Interventions
					Active	Comparator
Murr et al (2011).10,				38 patients with refractory CRS	Unilateral PROPEL steroid-eluting stent in the ethmoid sinus	Non-drug-eluting stent on the other contralateral side
Marple et al (2012)11,(ADVANCE II)				105 patients with refractory CRS	Unilateral PROPEL steroid-eluting stent in the ethmoid sinus	Non-drug-eluting stent on the contralateral side
Smith et al (2016)12,	US	11		80 patients with CRS who were scheduled to undergo primary or revision bilateral frontal sinusotomy	Unilateral PROPEL Mini Sinus Implant in the frontal sinus	Surgery alone on the contralateral side
Luong et al (2017)13,	US	12		80 patients with CRS who were scheduled to undergo primary or revision bilateral frontal sinusotomy	Unilateral PROPEL Contour Sinus Implant in the frontal sinus	Surgery alone on the contralateral side

CRS: chronic rhinosinusitis; RCT: randomized controlled trial.

Table 2. Summary of Key RCT Results

Study	Primary Outcome Measure	Polypoid Changes	Adhesions/scarring		Implant-Related Adverse Events
Murr et al (2011).10,	Degree of Inflammation at 21 Days Post-Procedure (100 mm VAS)
N	37	37
PROPEL steroid-eluting Stent		18.4%	5.3%
Non-steroid-eluting stent		36.8%	21.1%
Diff	18 points
p-value	NR	0.039	0.03
Marple et al (2012)11,	Need for Post-Operative Intervention Determined by 3 Independent Reviewers
N	91
PROPEL steroid-eluting Stent	33.3%
Non-steroid-eluting stent	46.9%
Diff	13.6%
p-value	0.028
Smith et al (2016)12,	Need for Post-Operative Intervention at 30 Days (Independent Reviewer) n (%)	Need for Post-Operative Intervention at 90 Days		Occlusion/ Restenosis Rate at Day 30
N	67 (adequate video for independent review)	79
PROPEL mini-sinus steroid-eluting stent	26 (38.8%)			16 (21.1%)	none
SOC without a stent	42 (62.7%)			35 (46.1%)
p-value	0.007	0.013	0.023	<0.001
Luong et al (2017)13,	Need for Post-Operative Intervention at 30 Days (Independent Reviewer) n (%)	Need for Surgical Intervention at 30 Days (Independent Reviewer) n (%)		Occlusion/ Restenosis Rate at Day 90
N	61	58		69
PROPEL Contour steroid-eluting stent	7 (11.5)	4 (6.9)		16 (23.2)
SOC without a stent	20 (32.8)	15 (25.9)		28 (40.6)
Diff (95% CI)	21.3% (35.1% to 7.6%)	19.0% (32.8% to 5.1%)		−17.4% (−28.6% to −6.1%)
NNT	4.7
Summary	Range 13.6% to 23.9%

CI: confidence interval; HR: hazard ratio; NNT: number needed to treat; NR: not reported; RCT: randomized controlled trial; SOC: standard of care.

Gaps in relevance and in design and conduct are shown in Tables 3 and 4. The primary gap for the Studies by Murr et al (2011) and Marple et al (2012) on the PROPEL implant in the ethmoid sinus was whether the comparator had received the optimal treatment in terms of packing, intranasal steroids, and irrigation. For the studies by Smith et al (2016) and Luong et al (2017), there was a high percentage of patients who were not able to be evaluated due to video quality.

Table 3. Relevance Gaps

Study	Populationa	Interventionb	Comparatorc	Outcomesd	Follow-Upe
Murr et al (2011).10,			3. The comparator may not have received the optimal treatment (some form of packing, intranasal steroids, and irrigation)
Marple et al (2012)11,			3. The comparator may not have received the optimal treatment (some form of packing, intranasal steroids, and irrigation)
Smith et al (2016)12,
Luong et al (2017)13,

The evidence gaps stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.

a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.

b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. the intervention of interest.

c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.

d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.

e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 4. Study Design and Conduct Gaps

Study	Allocationa	Blindingb	Selective Reportingc	Data Completenessd	Powere	Statisticalf
Murr et al (2011).10,		3. Outcome assessed by treating physician
Marple et al (2012)11,
Smith et al (2016)12,			2. Incomplete reporting of secondary outcomes	1. 12 (17%) patients did not have independent review at 30 days due to suboptimal video quality.
Luong et al (2017)				1. 19 (24%) patients did not have independent review at 30 days due to suboptimal video quality.

The evidence gaps stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.

a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.

b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.

c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.

d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).

e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.

f Statistical key: 1. Analysis is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Analysis is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated.

Nonrandomized Comparative Studies

The largest nonrandomized study identified was reported by Xu et al (2016).^14, It evaluated post-ESS synechiae formation among 146 patients (252 nasal cavities) treated with a steroid-eluting absorbable spacer and 128 patients (233 nasal cavities) treated with a nonabsorbable spacer. Eligible patients included those who underwent ESS (at minimum, maxillary antrostomy and anterior ethmoidectomy) for CRS with or without nasal polyps and were treated with a sinus spacer. Rates of synechiae formation at 1 month postoperatively did not differ significantly between groups (5 [2.0%] nasal cavities in the absorbable stent group vs 13 [5.6%] nasal cavities in the nonabsorbable spacer group).

Section Summary: Steroid-Eluting Stents as an Adjunct to ESS

The most direct evidence relating to use of steroid-eluting nasal stents as an adjunct to ESS comes from 4 RCTs comparing steroid-eluting stents with either a non-steroid-eluting stent or medical management. The need for post-operative intervention at 30 days was reduced by 14% to 24%, translating to a number needed to treat of 4.7 or more. Three trials used blinded assessors to evaluate postimplantation sinus changes, an important strength, but the trials had potentials for bias. To most accurately evaluate the benefit from PROPEL devices it is important to ensure that the comparison group is not undertreated (ie, receives some form of packing, intranasal steroids, and irrigation).

Steroid-Eluting Stents for Recurrent Polyposis

Clinical Context and Therapy Purpose

The purpose of steroid-eluting stents in patients who have recurrent polyposis is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: does the use of steroid-eluting stents improve the net health outcome in patients with recurrent polyposis?

The following PICOTS were used to select literature to inform this review.

Patients

The relevant population of interest are patients with recurrent polyposis after ESS.

Interventions

The therapy being considered is steroid-eluting stent (eg, SINUVA).

This stent is bioresorbable and softens over time, but needs to be removed by 90 days.

Comparators

A sham treatment may be used to determine whether active treatment reduces the need for ESS.

Outcomes

The general outcomes of interest are symptoms, anatomic outcomes, and need for additional ESS. These outcomes may be measured by the nasal obstruction/congestion score change (scale 0–3), polyp grade change (scale 0 to 8), ethmoid sinus obstruction change (scale 0–100), and the percentage of patients still indicated for repeat sinus surgery.

A beneficial outcome would be an improvement in symptoms and reduction in repeat ESS.

A harmful outcome would be adverse events from the implantable stents.

Timing

The steroid-eluting stents are kept in place for up to 90 days. Relevant outcomes would be measured at 90 days to evaluate the short-term effects of the treatment and at one or two years to evaluate the durability of this treatment.

Setting

The setting is outpatient care by an otolarygologist.

Review of Evidence

Two sham-controlled RCTs (RESOLVE and RESOLVE II) with a total of 400 patients have addressed outcomes after placement of steroid-eluting absorbable sinus stents in the office setting due to recurrent or persistent nasal polyposis after ESS (see Tables 5 and 6).^15,16,

In RESOLVE, For endoscopically measured outcomes, at 90 days of follow-up, the treatment group had a greater reduction in polyp grade than the control group (-1.0 vs -0.1; p=0.016) and a greater reduction in percent ethmoid obstruction on a 100-mm VAS (-21.5 mm vs 1.3 mm; p=0.001), both respectively. For patient-reported outcomes, there were no significant differences in change in nasal obstruction/congestion scores between groups. In RESOLVE II the implant group showed significant reductions in nasal congestion, polyp grade, and ethmoid obstruction at 90 days compared to sham controls. Out of 200 patients treated with the implant, 39% were indicated for sinus surgery at 3 months compared to 63.3% of controls (p<0.001)

Table 5. Summary of Key RCT Characteristics

Study; Trial	Countries	Sites	Dates	Participants	Interventions
					Active	Comparator
Han et al (2014)15,; RESOLVE				100 patients with recurrent nasal polyposis after ESS who had chronic rhinosinusitis, had undergone prior bilateral total ethmoidectomy more than 3 months earlier, had endoscopically confirmed recurrent bilateral ethmoid sinus obstruction due to polyposis that was refractory to medical therapy, and were considered candidates for repeat surgery based on the judgment of the surgeon and patient.	53 patients who received office-based placement of a mometasone-eluting nasal stent	47 patients who received sham treatment
Kern et al (2018)16,; RESOLVE II	US	34	2014-2016	300 adults with refractory chronic rhinosinusitis with nasal polyps who were candidates for repeat surgery. To be indicated for repeat ESS, a patient had to: (1) be using intranasal corticosteroid daily ; (2) receive at least 1 course of high-dose steroid therapy  or refused such therapy due to side effects within the past 1 year; (3) continue to have moderate-to-severe symptoms of nasal obstruction/congestion ; and (4) have endoscopic evidence of bilateral ethmoid sinus obstruction due to polyposis.	201 patients who received a SINUVA(TM) mometasone-eluting bioabsorbable nasal stent	99 patients who received sham treatment consisting of insertion and removal of implants

ESS: endoscopic sinus surgery; RCT: randomized controlled trial.

Table 6. Summary of Key RCT Results

Study	Nasal obstruction/congestion score change (scale 0–3)	Change in Polyp Grade at 90 Days (scale 0 to 8)	Reduction in Ethmoid Obstruction (scale 100) at 90 Days	Patients Indicated for Sinus Surgery at 3 months n (%)
Han et al (2014)15,; RESOLVE
Drug-eluting nasal stent		-1.0	-21.5 mm	47%
Sham		-0.1	1.3 mm	77%
P-value		0.016	0.001	NR
Kern et al (2018)16,; RESOLVE II
Drug-eluting nasal stent mean (SD)	−0.80 (0.73)	−0.56 (1.06)	−11.3 (18.1)	78/200 (39.0%)
Sham mean (SD)	−0.56 (0.62)	−0.15 (0.91)	−1.9 (14.4)	62/98 (63.3%)
Diff or OR (95% CI)	−0.23 (−0.39 to −0.06)	−0.35 (−0.60 to −0.09)	−7.96 (−12.10 to −3.83)	2.69 (1.63 to 4.44)
P-value	0.007	0.007	<0.001	<0.001

CI: confidence interval; NR: not reported; OR: odds ratio; RCT: randomized controlled trial.

Gaps in relevance and design and conduct are shown in Tables 7 and 8. A major limitation of the trials was the short duration of follow-up to determine the durability of the treatment. In addition, there is a potential for bias since outcomes were evaluated by the treating physician.

Table 7. Relevance Gaps

Study	Populationa	Interventionb	Comparatorc	Outcomesd	Follow-Upe
Han et al (2014)15,; RESOLVE					1. The 90 day follow-up is insufficient to evaluate the durability of this treatment.
Kern et al (2018)16,; RESOLVE II					1. The 90 day follow-up is insufficient to evaluate the durability of this treatment.

The evidence gaps stated in this table are those notable in the current review; this is not a comprehensive gaps assessment. Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.

b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. the intervention of interest.

c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.

d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.

e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 8. Study Design and Conduct Gaps

Study	Allocationa	Blindingb	Selective Reportingc	Data Completenessd	Powere	Statisticalf
Han et al (2014)15,; RESOLVE		3. Outcomes were assessed by the treating physician				3. Statistics were not reported for some outcome measures.
Kern et al (2018)16,; RESOLVE II		3. Polyp grade and sinus obstruction were assessed by the treating physician

The evidence gaps stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.

a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.

b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.

c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.

d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).

e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.

f Statistical key: 1. Analysis is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Analysis is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated.

Section Summary: Steroid-Eluting Stents for Recurrent Polyposis

One RCT was identified evaluating the use of steroid-eluting nasal stents for recurrent or persistent nasal polyposis after ESS, which demonstrated improvements in polyp grade and ethmoid obstruction. Strengths of this trial included use of a sham control and adequate power for its primary outcome. However, the trial had a high risk of bias due to unblinded outcome assessment. Although avoidance of repeat ESS and oral steroids may be relevant outcomes for this indication, it would be more important if decisions about repeat ESS or other treatments were standardized and, in the trial setting, if decisions were prespecified or made by a clinician blinded to treatment group. Sinus stents may prove to have a role in nasal polyposis; however, additional positive results from well-designed RCTs are needed to confirm the results of the single available RCT.

Summary of Evidence

For individuals who have chronic rhinosinusitis who have undergone ESS who receive implantable steroid-eluting sinus stents, the evidence includes RCTs. Relevant outcomes are symptoms, change in disease status, morbid events, and treatment-related morbidity. The most direct evidence relating to use of steroid-eluting nasal stents as an adjunct to ESS comes from 4 RCTs comparing steroid-eluting stents with either a non-steroid-eluting stent or medical management. The need for post-operative intervention at 30 days was reduced by 14% to 24%, translating to a number needed to treat of 4.7 or more. Three trials used blinded assessors to evaluate postimplantation sinus changes, an important strength, but the trials had potentials for bias. To most accurately evaluate the benefit from PROPEL devices it is important to ensure that the comparison group is not undertreated (ie, receives some form of packing, intranasal steroids, and irrigation). The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have recurrent sinonasal polyposis who have undergone endoscopic sinus surgery who receive implantable steroid-eluting sinus stents, the evidence includesRCTs. Relevant outcomes are symptoms, change in disease status, morbid events, and treatment-related morbidity. Two RCTs were identified evaluating the use of steroid-eluting nasal stents for recurrent or persistent nasal polyposis after ESS, which demonstrated improvements in polyp grade and ethmoid obstruction. Strengths of these trials included use of a sham control and adequate power for its primary outcome. However, the trials had a high risk of bias due to unblinded outcome assessment. Although avoidance of repeat ESS and oral steroids may be relevant outcomes for this indication, it would be more important if decisions about repeat ESS or other treatments were standardized and, in the trial setting, if decisions were prespecified or made by a clinician blinded to treatment group. Sinus stents may prove to have a role in nasal polyposis; however, further follow-up is needed to evaluate the durability of the results.. The evidence is insufficient to etermine the effects of the technology on health outcomes.

SUPPLEMENTAL INFORMATION

Clinical Input From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received from 1 physician specialty society and 4 academic medical centers while this policy was under review in 2012. Input overall was mixed, without consensus among respondents. Some reviewers expressed support for use of these devices after endoscopic sinus surgery. Reviewers who supported use cited the randomized controlled trials reviewed in this review as the main source of evidence. Other reviewers did not support use in general following endoscopic sinus surgery, arguing that a subset of patients may benefit, but there was no consensus on which populations this subgroup would include.

Practice Guidelines and Position Statements

No guidelines or statements were identified.

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

A search of clinicaltrials.gov in February, 2019 did not identify any trials that would likely influence this review.]
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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Steroid-Eluting Sinus Stents
Implantable Sinus Stents for Postoperative Use Following Endoscopic Sinus Surgery
Implantable Sinus Spacers and Stents for Postoperative Use Following Endoscopic Sinus Surgery
Sinus Stents, Steroid-Eluting
Stents, Sinus, Steroid-Eluting
Relieva Stratus MicroFlow
Propel Device
SINUVA™ Sinus Implant

References:
1. Sedaghat AR. Chronic rhinosinusitis. Am Fam Physician. Oct 15 2017;96(8):500-506. PMID 29094889

2. Rudmik L, Soler ZM, Orlandi RR, et al. Early postoperative care following endoscopic sinus surgery: an evidence-based review with recommendations. Int Forum Allergy Rhinol. Nov-Dec 2011;1(6):417-430. PMID 22144050

3. Berlucchi M, Castelnuovo P, Vincenzi A, et al. Endoscopic outcomes of resorbable nasal packing after functional endoscopic sinus surgery: a multicenter prospective randomized controlled study. Eur Arch Otorhinolaryngol. Jun 2009;266(6):839-845. PMID 18946677

4. Cote DW, Wright ED. Triamcinolone-impregnated nasal dressing following endoscopic sinus surgery: a randomized, double-blind, placebo-controlled study. Laryngoscope. Jun 2010;120(6):1269-1273. PMID 20513050

5. Freeman SR, Sivayoham ES, Jepson K, et al. A preliminary randomised controlled trial evaluating the efficacy of saline douching following endoscopic sinus surgery. Clin Otolaryngol. Oct 2008;33(5):462-465. PMID 18983380

6. Rotenberg BW, Zhang I, Arra I, et al. Postoperative care for Samter's triad patients undergoing endoscopic sinus surgery: a double-blinded, randomized controlled trial. Laryngoscope. Dec 2011;121(12):2702-2705. PMID 21997904

7. Rudmik L, Mace J, Mechor B. Effect of a dexamethasone Sinu-FoamTM middle meatal spacer on endoscopic sinus surgery outcomes: a randomized, double-blind, placebo-controlled trial. Int Forum Allergy Rhinol. Jan 17 2012;2(3):248-251. PMID 22253199

8. Lee JM, Grewal A. Middle meatal spacers for the prevention of synechiae following endoscopic sinus surgery: a systematic review and meta-analysis of randomized controlled trials. Int Forum Allergy Rhinol. Nov 2012;2(6):477-486. PMID 22648984

9. Huang Z, Hwang P, Sun Y, et al. Steroid-eluting sinus stents for improving symptoms in chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery. Cochrane Database Syst Rev. Jun 10 2015;6(6):CD010436. PMID 26068957

10. Murr AH, Smith TL, Hwang PH, et al. Safety and efficacy of a novel bioabsorbable, steroid-eluting sinus stent. Int Forum Allergy Rhinol. Jan-Feb 2011;1(1):23-32. PMID 22287304

11. Marple BF, Smith TL, Han JK, et al. Advance II: a prospective, randomized study assessing safety and efficacy of bioabsorbable steroid-releasing sinus implants. Otolaryngol Head Neck Surg. Jun 2012;146(6):1004-1011. PMID 22301107

12. Smith, TT, Singh, AA, Luong, AA, Ow, RR, Shotts, SS, Sautter, NN, Han, JJ, Stambaugh, JJ, Raman, AA. Randomized controlled trial of a bioabsorbable steroid-releasing implant in the frontal sinus opening. Laryngoscope, 2016 Jul 2;126(12). PMID 27363723

13. Luong, AA, Ow, RR, Singh, AA, Weiss, RR, Han, JJ, Gerencer, RR, Stolovitzky, JJ, Stambaugh, JJ, Raman, AA. Safety and Effectiveness of a Bioabsorbable Steroid-Releasing Implant for the Paranasal Sinus Ostia: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg, 2017 Nov 4. PMID 29098299

14. Xu JJ, Busato GM, McKnight C, et al. Absorbable steroid-impregnated spacer after endoscopic sinus surgery to reduce synechiae formation. Ann Otol Rhinol Laryngol. Mar 2016;125(3):195-198. PMID 26391092

15. Han JK, Forwith KD, Smith TL, et al. RESOLVE: a randomized, controlled, blinded study of bioabsorbable steroid-eluting sinus implants for in-office treatment of recurrent sinonasal polyposis. Int Forum Allergy Rhinol. Nov 2014;4(11):861-870. PMID 25266981

16. Kern, RR, Stolovitzky, JJ, Silvers, SS, Singh, AA, Lee, JJ, Yen, DD, Iloreta, AA, Langford, FF, Karanfilov, BB, Matheny, KK, Stambaugh, JJ, Gawlicka, AA. A phase 3 trial of mometasone furoate sinus implants for chronic sinusitis with recurrent nasal polyps. Int Forum Allergy Rhinol, 2018 Jan 20;8(4). PMID 29350840

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

0406T
0407T

C9122
J7401