Standalone balloon dilation versus sinus surgery for chronic rhinosinusitis: A prospective, multicenter, randomized, controlled trial with 1-year follow-up Nadim Bikhazi, M.D.,1 Joshua Light, M.D.,2 Theodore Truitt, M.D.,3 Michael Schwartz, M.D.,4 Jeffrey Cutler, M.D.,5 and REMODEL Study Investigators

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ABSTRACT

Background: The objective of this prospective, multicenter, randomized trial was to evaluate and compare 1-year outcomes from the REMODEL study between office balloon dilation and functional endoscopic sinus surgery (FESS). Methods: Adults with maxillary chronic rhinosinusitis (CRS), including those with anterior ethmoid disease, who failed medical management and were surgical candidates for FESS, underwent either standalone balloon dilation or FESS in a 1:1 randomization scheme and were followed through a minimum of 1 year. Sinonasal symptom improvement was assessed using the validated 20-item Sino-Nasal Outcome Test (SNOT-20) survey. Standardized effect sizes were computed to further assess clinical significance. Ostial patency rate, rhinosinusitis episode frequency, impact of sinus disease on activity and work productivity using the validated Work Productivity and Activity Impairment survey, complications, and revision rate were also compared between the two groups. Results: Ninety-two patients (50 balloon dilation; 42 FESS) were treated and 89 (96.7%) completed 1-year follow-up. Both groups showed clinically meaningful and statistically significant (p ⬍ 0.0001) improvement in mean overall SNOT-20 scores and in all four SNOT-20 subscales. The 1-year mean change in SNOT-20 after balloon dilation (⫺1.64) was noninferior to FESS (⫺1.65; p ⬍ 0.001). The standardized effect size was large, showing clinically significant improvement for both interventions. Ostial patency was 96.7 and 98.7% after balloon dilation and FESS, respectively, and each group reported significant reductions (p ⬍ 0.0001) in rhinosinusitis episodes (mean decrease, 4.2 for balloon dilation and 3.5 for FESS). Overall work productivity and daily activity impairment due to chronic sinusitis were significantly improved (p ⬍ 0.001) in both groups. There were no complications and revision surgery rate was 2% in each arm through 1 year. Conclusion: With 1-year follow-up, standalone balloon dilation is as effective as FESS in the treatment of CRS in patients with maxillary sinus disease with or without anterior ethmoid disease who failed medical therapy and met the criteria for medically necessary FESS. (Am J Rhinol Allergy 28, 323–329, 2014; doi: 10.2500/ajra.2014.28.4064)

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e previously published 6-month results from a large, prospective, randomized trial REMODEL sufficiently powered to compare outcomes in patients who failed medical management, met symptom- and evidence-based chronic rhinosinusitis (CRS) guidelines, and also met criteria for medically necessary functional endoscopic sinus surgery (FESS) for uncomplicated rhinosinusitis.1 We showed that patients in the balloon dilation arm required significantly fewer debridements than FESS patients, showing superiority of the balloon group. We also showed the occurrence of postoperative nasal bleeding, duration of prescription pain medication use, recovery time, and short-term symptom improvement were all significantly better after balloon dilation compared to FESS. At 6 months, symptom improvement from baseline was significantly improved in both arms while the magnitude of improvement between the two arms was similar; i.e., balloon dilation improvement was noninferior to FESS. No complications occurred and durability was established through very low revision surgery rates of 2% in each arm. The objective of this randomized trial, the REMODEL study, was to evaluate and compare 1-year outcomes between office balloon dilation and FESS. We evaluated sinonasal symptom improvement, rhinosinusitis episodes, ostial patency, work productivity and activity, com2

From the Ogden Clinic, Ogden, Utah, Ear, Nose, and Throat Associates of South Florida, Boynton Beach, Florida, 3St. Cloud Ear, Nose, and Throat, St. Cloud, Minnesota, 4Ear, Nose, and Throat Associates of South Florida, West Palm Beach, Florida, and 5 Associates of Otolaryngology, Denver, Colorado Funded by Entellus Medical, Inc. T Truitt and J Cutler are paid consultants to and stockholders of Entellus Medical. The remaining authors have no conflicts of interest to declare pertaining to this article Address correspondence to Nadim Bikhazi, M.D., Ogden Clinic, 4650 Harrison Boulevard, Ogden, UT 84403 E-mail address: [email protected] Published online May 12, 2014 Copyright © 2014, OceanSide Publications, Inc., U.S.A.

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plications, and revision surgery rate 1-year post–balloon dilation versus FESS.

MATERIALS AND METHODS Study Overview This study REMODEL was designed as a prospective, multicenter, open-label, randomized, controlled trial. The randomization was oneto-one between balloon dilation and control (FESS). Institutional Review Board approval was obtained for each investigational site and all patients provided voluntary informed consent before enrollment. Each investigator was board certified in otolaryngology and had experience with both balloon dilation and FESS procedures. Investigators were not blinded to treatment assignment. The randomization process, independent physician review and oversight, and study procedures were previously described.1 The protocol required postoperative follow-up assessments for all patients at 1 week and 1, 3, 6, and 12 months, and every 6 months thereafter until study closure.

Inclusion and Exclusion Criteria Eligible patients were at least 18 years of age and had CRS per the 2007 adult sinusitis clinical practice guidelines.2 All patients had maxillary sinus disease with or without anterior ethmoid disease. Each patient also met the criteria for medically necessary FESS for uncomplicated rhinosinusitis per either the Anthem Coverage Guideline (CG-SURG-24; December 2011)3 or BlueCross BlueShield of North Carolina Medical Policy (August 2011),4 as previously described.1 Patients with posterior ethmoid, sphenoid, or frontal rhinosinusitis requiring FESS or balloon dilation, as well as those with fungal sinusitis, severely deviated septum causing complete obstruction, or gross sinonasal polyposis were excluded. Patients who had previously undergone sinus surgery, those who underwent nasal

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surgery within 3 months before randomization, and anyone requiring concomitant sinonasal surgery at the time of the study procedure (e.g., septoplasty) were not eligible. Patients with ciliary dysfunction or Samter’s triad along with individuals either undergoing chemotherapy in the head/neck region or who were pregnant were also excluded from study participation.

Primary Endpoint

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The primary endpoint was long-term improvement in sinonasal symptoms as assessed by the mean change in overall 20-item SinoNasal Outcome Test (SNOT-20) score from baseline. The SNOT-20 is a validated quality-of-life (QOL) outcome measure specifically for patients with rhinosinusitis.5–7 Patients rate the severity of 20 different symptoms on a scale of 0 (no problem) to 5 (problem as bad as it can be). The 20 symptoms were further analyzed per the following four validated subscales: rhinologic symptoms, ear/facial symptoms, sleep function, and psychological issues.7 A decrease of ⱖ0.8 of the mean SNOT-20 score is considered clinically meaningful.5 To further assess clinically relevant or significant change over time, standardized effect sizes were computed for the change in SNOT-20 scores. The standardized effect size is calculated by dividing the mean change score by its SD.7–9 An effect size (absolute value) of ⬍0.5 is considered a small effect, 0.5 to ⬍0.8 is considered a moderate effect, and ⱖ0.8 is considered a large effect. These ranges have been validated for patient-reported symptoms.7–9

Figure 1. Participant flow diagram.

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Secondary Outcomes Secondary outcomes assessed at 1 year included change in number of rhinosinusitis episodes, ostial patency, change in work productivity and activity, complications, and revision surgery rate. The number of patient-reported rhinosinusitis episodes that occurred 1 year before the balloon dilation or FESS procedure was compared with those that occurred 1 year postprocedure. At baseline patients reported how many separate rhinosinusitis episodes requiring medication they had during the prior year. The number of separate rhinosinusitis episodes requiring medication the year of postprocedure was based on the patient-reported antibiotics taken to treat their sinus disease throughout the study. Ostial patency at 1-year follow-up was assessed using computed tomography scans. Radiographic assessment of patency was chosen over nasal endoscopy as attempts to visualize the maxillary ostium with the uncinate process intact were not well tolerated by patients. The protocol required computed tomography scan acquisition of coronal images using contiguous 2 ⫻ 2-mm slices at a minimum and taken perpendicular to the hard palate. Most scans included axial and sagittal images as well. An ostium was defined as patent when the maxillary ostium and entire length of the ethmoid infundibulum was unobstructed and open. Changes in work productivity and activity were measured by the validated Work Productivity and Activity Impairment (WPAI)10 survey between baseline and 1-year follow-up. The validated six-question WPAI was used to measure changes in regular daily activity impairment, work time missed, on-the-job impairment, and overall work impairment due to CRS. WPAI results are reported as percentages of time where a larger number indicates greater impairment. A complication was defined as a serious device-related or procedure-related adverse event. Revision surgery was defined as surgery on any sinus initially treated during the study procedure or surgery on a previously untreated sinus.

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Sample Size and Statistical Analysis Sample size was calculated using PASS 2008 as previously reported.1,11 A minimum of 36 subjects per arm were required to show noninferiority in symptom improvement (SNOT-20) between balloon dilation and FESS with 90% power using a margin of 0.8 at a one-

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Figure 2. One-year change in 20-item Sino-Nasal Outcome Test (SNOT20) score from baseline by study arm. The p value based on a one-sided Student’s t-test, with a noninferiority margin of 0.8. Statistical significance is determined by comparing the p value at the 1-year time point to 0.025. The mean 1-year improvement in SNOT-20 score for patients undergoing balloon dilation is not inferior to that for patients undergoing functional endoscopic sinus surgery (FESS).

Figure 3. One-year mean 20-item Sino-Nasal Outcome Test (SNOT-20) score by study arm. Mean overall SNOT-20 score for each study arm is based on matched-pair data at baseline and 1-year follow-up. sided ␣-level of 0.025. One-sided Student’s t-test was used to compare this enpoint between study arms. Secondary outcomes were evaluated for superiority using two-sided Student’s t-tests to compare continuous measures and Fisher’s exact tests to compare categorical measures. The values of p ⬍ 0.05 were considered statistically significant. All analyses were performed using SAS Version 9.3 (SAS Institute, Cary, NC).

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Table 1 Change in SNOT-20 symptom subscales from baseline to 1-yr posttreatment by study arm Subscale

Balloon Dilation (n ⴝ 46) Baseline

Rhinologic symptoms Ear and facial symptoms Sleep function Psychological issues

Control (FESS) (n ⴝ 40)

1-yr Standardized Effect p Value* Baseline 1-yr Standardized Effect Change Size§ Change Size§

2.56 2.61 2.60 2.38

⫺1.44 ⫺1.86 ⫺1.59 ⫺1.67

⫺1.2(large) ⫺1.6(large) ⫺0.9(large) ⫺1.2(large)

⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001

2.91 2.11 2.89 2.27

⫺1.89 ⫺1.44 ⫺1.79 ⫺1.58

⫺2.0(large) ⫺1.2(large) ⫺1.1(large) ⫺1.4(large)

p Value# p Value* ⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001

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*Comparison of mean change from baseline to follow-up within subgroup; p value from paired t-test. #Comparison of difference between study arms; p value from two-sample t-test. §Standardized effect size: small, ⬍0.5; moderate, 0.5 to ⬍0.8; large, ⱖ0.8. FESS ⫽ functional endoscopic sinus surgery; SNOT-20 ⫽ 20-item Sino-Nasal Outcome Test; NS ⫽ not significant.

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Sinonasal Symptoms

RESULTS Participant Flow

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Between December 2011 and December 15, 2012, 92 adults at 10 sites were enrolled and underwent treatment of balloon dilation (50) or FESS (42) as previously described.1 A total of 89 patients (48 balloon dilation; 41 FESS; 96.7%) completed 1-year follow-up (Fig. 1). The 3 patients who did not complete 1-year follow-up all showed symptom improvements (change in SNOT-20 score, ⫺1.70, ⫺2.20, and ⫺2.95) and none of these patients had any revision surgery as of their last follow-up. Baseline characteristics were previously reported and there were no significant differences between patients randomized to balloon dilation or FESS.1

Baseline mean (⫾SD) SNOT-20 scores were 2.54 ⫾ 0.92 in the balloon dilation arm and 2.52 ⫾ 0.79 in the FESS arm. Mean improvement in SNOT-20 score at 1 year was ⫺1.64 ⫾ 1.06 in the balloon arm and ⫺1.65 ⫾ 0.94 in the FESS arm. Figure 2 shows a comparison of the mean changes in SNOT-20 score between the two study arms at 1 year. The difference between groups was 0.01 (95% CI, ⫺0.43 to 0.44). The upper bound of the 95% CI for the difference is less than the prespecified noninferiority margin of 0.8. Thus, sinonasal symptom improvement in patients 1 year after balloon dilation was noninferior to FESS (p ⬍ 0.001). Both study groups experienced clinically meaningful and statistically significant (p ⬍ 0.0001) improvement that was maintained from 1 month to 1 year posttreatment (Fig. 3). Overall, 80.4% of the balloon arm and 80.0% of the FESS arm had clinically meaningful sinonasal symptom improvement at 1 year. In addition, the standard effect size was large for the overall SNOT-20 score at 1 year for both groups, providing further evidence of a clinically significant change. Sinonasal symptom improvement across all SNOT-20 subscales was also clinically meaningful and statistically significant (p ⬍ 0.0001) for both study arms at 1 year. There was a large treatment effect size in each of the four SNOT-20 subscales as shown in Table 1 and there was no difference in improvement in any of the subscales between the two study arms (p ⫽ NS). We previously observed statistically significant (p ⬍ 0.0001) and clinically meaningful improvement in mean SNOT-20 scores in both treatment arms at 6-month follow-up for four different subgroup analyses: sinus disease location (maxillary; anterior ethmoid), presence or absence of accessory ostia, presence or absence of septal deviation, or CRS diagnosis (chronic; recurrent acute).1 At 1 year, symptom improvement in each of the four subgroups remained statistically significant (p ⬍ 0.001) in both treatment arms and there was no difference (p ⫽ NS) in improvement between patients who underwent balloon dilation or FESS.

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Figure 4. Mean number of rhinosinusitis episodes requiring medication by study arm. Balloon dilation versus control (functional endoscopic sinus surgery [FESS]; p ⫽ NS).

NS NS NS NS

Balloon Dilation versus FESS Patients randomized to balloon dilation underwent standalone balloon dilation of the maxillary ostium and ethmoid infundibulum under local anesthesia in the office. Patients randomized to FESS underwent conventional endoscopic maxillary antrostomy and uncinectomy with or without anterior ethmoidectomy per surgeon discretion. In the 42-patient FESS arm, 80 maxillary antrostomies with uncinectomies were completed (38 bilateral and 4 unilateral). Of the 80 uncinectomies, 72 were total and 8 were partial. A majority of FESS patients (35; 80.2%) underwent bilateral total uncinectomy. A total of 41 concomitant anterior ethmoidectomies (19 bilateral and 3 unilateral) were performed in 22 patients. No other sinonasal procedures were permitted.

Rhinosinusitis Episodes In the 1-year period before treatment, patients in the balloon dilation arm reported a mean of 5.2 ⫾ 2.8 rhinosinusitis episodes requiring medication and patients in the FESS arm reported a mean of 4.5 ⫾ 1.8 episodes (p ⫽ NS). During the 1-year postprocedure, both study groups reported a mean of 1.0 rhinosinusitis episodes per patient, a reduction of 4.2 episodes in the balloon arm and a reduction of 3.5 episodes in the FESS arm. The reduction in the mean number of reported sinusitis episodes was statistically significant (p ⬍ .0001) in both arms and there was no difference between treatment arms (p ⫽ NS; Fig. 4).

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tion was not significant (p ⫽ 0.169). The change from baseline to 1-year follow-up in each arm for all four WPAI measures is shown in Table 2.

Ostial Patency A total of 47 balloon dilation patients (91 maxillary ostia) and 41 FESS patients (78 maxillary ostia) had an evaluable computed tomography scan at 1 year. Overall patency at 1 year was 96.7% (88/91) in the balloon arm and 98.7% (77/78) in the FESS arm (Fig. 5). There was no significant difference in patency rates between the two groups (p ⫽ NS).

Complications and Revision Surgery We previously reported no complications in either arm and one revision surgery in each arm through 6 months.1 No additional complications or revision surgeries were reported through 1 year. Our 0% complication rate is unchanged and the revision rates in the balloon and FESS arms also remain similar at 2.1 and 2.4%, respectively, at 1-year postprocedure. A description of each revision procedure was previously reported.1

Work Productivity and Activity The extent that rhinosinusitis limited daily activity and work productivity was significantly reduced after treatment. Patients in both study arms reported a statistically significant reduction of regular daily activity impairment due to CRS (52% at baseline versus 11% at 1 year; p ⬍ 0.0001). In the balloon arm, patients who worked reported significantly less missed work time (p ⬍ 0.001), significantly less on-the-job impairment (“presenteeism”; p ⬍ 0.0001), and significantly less overall work impairment (p ⬍ 0.0001) because of their rhinosinusitis. Patients who underwent FESS reported similar, significant (p ⬍ 0.0001) improvement in “presenteeism” and overall work impairment. FESS patients also saw absenteeism drop but the reduc-

The first 45 patients treated in our study had a postprocedure follow-up duration of ⱖ18 months. Of these 45 patients, 43 (22 balloon dilation; 21 FESS) (95.6%) completed their 18-month follow-up and their results are presented here. Baseline sinonasal symptom severity was similar between treatment arms with a mean (⫾SD) overall SNOT-20 score of 2.64 ⫾ 0.95 in the balloon group and 2.62 ⫾ 0.60 in the FESS group (p ⫽ NS). At 18-month follow-up, a mean (⫾SD) decrease in SNOT-20 of ⫺1.81 ⫾ 1.00 in the balloon group and ⫺1.39 ⫾ 1.13 in the FESS group were both clinically meaningful and statistically significant (p ⬍ 0.0001). There was a large treatment effect size in the SNOT-20 score at 18 months and sinonasal symptom improvement was sustained from 1 month to 1.5 years for both study arms (Fig. 6). No complications were reported in either group. Sixteen months (postoperative day 476) after treatment, one FESS patient underwent an additional procedure (bilateral balloon dilation of the frontal sinuses and unilateral balloon dilation of the right sphenoid sinus) to treat medically refractory sinus symptoms and radiographic evidence of sinus inflammation and ostial narrowing of the frontal and sphenoid sinuses. No additional revision surgeries occurred in the balloon arm.

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Figure 5. One-year patency rate by study arm. Balloon dilation versus control (functional endoscopic sinus surgery [FESS]; p ⫽ NS).

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Eighteen-Month Follow-up Results

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DISCUSSION This study used the validated SNOT-20 survey to measure quantitative improvement in patient sinonasal symptoms. Pynnonen et al. further validated the presence of the SNOT-20 subscales and concluded SNOT-20 analyzed by construct and standardized effect size provides a better understanding of the clinical impact of medical and surgical procedures for rhinosinusitis.7 In this REMODEL study comparing two interventions to treat patients with CRS unresponsive to medical management, we observed statistically significant improvement that was twice the clinically meaningful threshold, and a large standardized treatment effect size in each of the four SNOT-20 sub-

Table 2 Change in WPAI from baseline to 1 yr by study arm Symptom

n

Balloon Dilation Baseline

1 yr

Change

Control (FESS) p Value*

Activity impairment due to chronic sinusitis (all patients) Percent regular daily 46 51.7 11.3 ⫺40.4 ⬍0.0001 activity impairment Work productivity impairment due to chronic sinusitis (working patients only) Percent work time missed 29 6.5 0.0 ⫺6.5 ⬍0.001 Percent impairment while 29 46.9 9.3 ⫺37.6 ⬍0.0001 working Percent overall work 29 49.3 9.3 ⫺40.0 ⬍0.0001 impairment

p Value#

n

Baseline

1 yr

Change

p Value*

41

52.7

11.0

⫺41.7

⬍0.0001

NS

18 19

7.3 35.3

1.4 7.4

⫺5.9 ⫺27.9

0.169 ⬍0.0001

NS NS

18

38.9

8.6

⫺30.3

⬍0.001

NS

*Comparison of mean change from baseline to 1-yr follow-up within subgroup; p value from paired t-test. #Comparison of difference between study arms; p value from two-sample t-test. FESS ⫽ functional endoscopic sinus surgery; WPAI ⫽ work productivity and activity impairment; NS ⫽ not significant.

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Table 3 Mean change in SNOT-20 symptom scores from baseline to 1 yr posttreatment for standalone balloon dilation and FESS by study

Figure 6. Eighteen-month mean 20-item Sino-Nasal Outcome Test (SNOT20) score by study arm. Mean overall SNOT-20 score for each study arm is based on matched-pair data at baseline and 18-month follow-up.

scales as well as the overall SNOT-20 score. Mean SNOT-20 score at 1 year decreased by 1.64 in the balloon arm and by 1.65 in the FESS arm. The SNOT-20 has been previously used in multiple studies to assess SNOT-20 symptom improvement in patients who underwent FESS, an acceptable and established treatment for medically refractory CRS, or in patients who underwent standalone balloon multisinus dilation. These 10 studies, including 600 patients, have consistently shown mean SNOT-20 scores significantly decrease by ⬎1.0 at 1-year follow-up (Table 3).12–21 These data are consistent with and further affirm the large treatment effect shown in our REMODEL study. The durability of sinonasal symptom improvement as shown with the flat curves of Figs. 3 and 6 after standalone balloon dilation is not unique to this study but has been reported in six other studies that longitudinally reported SNOT-20 scores from initial follow-up to 1 or 2 years postprocedure.12–17,22,23 Of note, for the two studies that assessed the durability of symptom reduction of standalone balloon dilation at 2 years, the change in SNOT-20 symptom scores versus baseline remained constant with no more than 0.08 variation between 6, 12, and 24 month follow-up.22,23 Those results along with the consistent reduction of symptoms at 6, 12, and 18 months from our study show the durability of standalone balloon dilation. The socioeconomic burden of rhinosinusitis has been estimated to be $8.6 billion annually with antibiotic costs alone reaching $150 million/yr.24,25 Between 1 and 10% of patients who take antibiotics experience side effects such as skin rash, gastrointestinal upset, vomiting, or diarrhea and patients who require multiple rounds to treat recurring sinusitis episodes are likely to progress to higher-cost classes of antibiotics with an increased risk of developing antibiotic resistance and greater side effects.26 In this study, the number of reported rhinosinusitis episodes per patient requiring medication in the year before intervention was between four and five, which is similar to the general population of patients undergoing FESS or balloon dilation who report between three and four episodes in the year leading up to treatment.8,16,17,27,28 The large number of pretreatment rhinosinusitis episodes is not surprising because our study population met specific criteria before enrollment that included failure to improve despite multiple rounds of medical therapy. The significant reduction in the number of rhinosinusitis episodes requiring antibiotics in our study is consistent with other standalone balloon dilation studies and further shows the clinical usefulness and potential cost-savings of balloon dilation.16,17 Maxillary ostium scarring and restenosis after FESS is one of the leading causes of sinus surgery failure with up to one-quarter of all failures attributed to obstructed maxillary ostia.29–31 One prospective

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n

1 yr Change

p Value*

Balloon dilation REMODEL Kuhn12 Atkins13 Cutler14 Albritton15 Levine16 Gould17 Total Balloon Dilation

46 31 36 67 21 64 75 340

⫺1.64 ⫺1.06 ⫺1.3 ⫺1.8 ⫺1.43 ⫺1.2 ⫺1.57 ⫺1.47

⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.0001 ⬍0.001 ⬍0.0001 ⬍0.0001 ⬍0.0001

FESS REMODEL Colclasure18 Deal19 Bradley20 Lee21 Total FESS

41 56 123 113 14 347

⫺1.65 ⫺1.12 ⫺1.08 ⫺1.19 ⫺1.51 ⫺1.15

⬍0.0001 ⬍0.001 ⬍0.0001 ⬍0.0001 0.001 ⬍0.0001

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*The p value from paired t-test. FESS ⫽ functional endoscopic sinus surgery; SNOT-20 ⫽ 20-item SinoNasal Outcome Test.

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study reported 96% patency 3 months after standalone balloon dilation of maxillary ostia/ethmoid infundibula.32 Two additional prospective studies reported 92% patency of multisinuses 1 year after balloon dilation hybrid procedures.12,27 In this randomized study, we reported a similarly high patency rate (96.7%) of the maxillary ostia/ ethmoid infundibula 1 year after standalone balloon dilation. Maxillary antrostomy patency in the FESS treatment arm was also very high (98.7%) and there was no difference compared with the balloon arm (p ⫽ NS). Our data further show that uncinate-preserving remodeling of the bony structures within the maxillary ostium and ethmoid infundibulum is sustained through 1 year with only a 3% likelihood of recurring obstruction. This study has some limitations. QOL questionnaires may be subject to recall bias because they are based on patient-reported events. However, QOL surveys such as the SNOT-20 that assess static (i.e., specific point in time) symptom severity rather than symptom severity relative to a previous point in time are less likely to be impacted by recall bias. In addition, recall bias in this study appears to be unlikely because of the consistency of longitudinally reported SNOT-20 scores at 1 and 6 months and 1-year follow-up as shown in Fig. 3. Although blinding in a randomized study is preferred, this has not been the standard in studies comparing FESS with medical management, and patient blinding in our study was not possible to do because the balloon dilation group was treated while awake during local anesthesia and the FESS group was commonly treated using general anesthesia. In addition to reporting on the 1-year outcomes, a summary of all statistical analyses and outcomes of this study from short-term follow-up through 1 year is provided in Table 4.1 With 92 treated patients of which 89 (96.7%) were followed through 1 year, our evaluable sample size was 17 patients (24%) greater than the 36 per arm required to test the SNOT-20 primary endpoint with 90% power. The multiple efficacy endpoints in this study provide a belt and suspenders approach for evaluating the effectiveness of standalone balloon dilation compared with FESS. Both study arms showed a similar level of statistically significant improvement in each of the four SNOT-20 subscales and the overall SNOT-20 score that was twice the clinically meaningful threshold, and by standardized measures, showed a large treatment effect. Adding to the large treatment effect

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Table 4 REMODEL trial overall outcomes by study arm REMODEL Study Overall Outcomes

Balloon Dilation Control (FESS) p Value* Mean or % Mean or %

Primary end points 6-mo change in SNOT-20 1-yr change in SNOT-20 Number of debridements per patient Secondary outcomes (recovery and short term) Patients discharged with nasal bleeding Recovery time (days) Duration of prescription pain medications (days) Short-term change in SNOT-20 (1 wk/1 mo) Secondary outcomes (1 yr) Change in number of rhinosinusitis episodes per patient Ostial patency Mean reduction of activity impairment due to CRS Mean reduction in overall work impairment because of CRS Complications Revision surgery rate

⫺1.67 ⫺1.64 0.1

⫺1.60 ⫺1.65 1.2

28% 1.6 0.9

55% 4.8 2.8

⫺1.49/⫺1.70 ⫺4.2

Balloon Dilation vs Control (FESS)

⬍0.001 Balloon dilation noninferior to FESS ⬍0.001 Balloon dilation noninferior to FESS ⬍0.0001 Balloon dilation superior to FESS

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0.011 0.002 ⬍0.001

Balloon dilation significantly better than FESS Balloon dilation significantly better than FESS Balloon dilation significantly better than FESS

⫺0.96/⫺1.62

0.014

Balloon dilation significantly better than FESS

⫺3.5

NS

No significant difference between study arms

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96.7% 78%

98.7% 79%

NS NS

No significant difference between study arms No significant difference between study arms

81%

78%

NS

No significant difference between study arms

NS NS

No significant difference between study arms No significant difference between study arms

0% 2.1%

0% 2.4%

*Comparison of difference between study arms. CRS chronic rhinosinusitis; FESS ⫽ functional endoscopic sinus surgery; SNOT-20 ⫽ 20-item Sino-Nasal Outcome Test; NS ⫽ not significant.

seen with the SNOT-20 survey, there was a significant reduction in the number of reported rhinosinusitis episodes and very low surgical revision rates in the year after treatment. This further verifies the comparative effectiveness and durability of the balloon procedure relative to FESS. Because CRS has a significant impact on a person’s QOL and activities, the WPAI survey provided additional efficacy by showing a 78–81% reduction in activity impairment and work impairment, respectively, after balloon dilation treatment. The surgical revision rate stayed constant from 6 months to 1 year at a very low rate of 2%. Finally, objective evidence from computed tomography scans showing 97% ostial patency at 1 year further supports the patient reports of symptom improvement and the efficacy of balloon sinus dilation. Notably, in each instance where a statistical finding favored a treatment arm, it was in favor of the balloon group. The 1-year data from this well-powered randomized study affirms a large treatment effect from standalone balloon sinus dilation in patients with maxillary sinus disease with or without anterior ethmoid disease, providing further evidence of clinically significant symptom improvement that is similar in significance and magnitude as FESS as well as similar to the outcomes from six previous nonrandomized prospective studies of standalone balloon multisinus dilation that show highly significant (p ⬍ 0.0001) symptom improvement 1 year after standalone balloon dilation (Table 3).12–21

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CONCLUSION

This prospective, multicenter, randomized trial, now with 1-year results in addition to the 6-month results, shows that standalone balloon dilation performed in the physician office is proven to be safe, effective, and a beneficial alternative to FESS in patients with maxillary sinus disease with or without anterior ethmoid disease who fail medical management and meet the surgical criteria for uncomplicated CRS. The benefits of balloon dilation arise from faster patient recovery, fewer debridements, less bleeding, reduced use of postoperative pain medication, and occur in conjunction with comparable efficacy as FESS in terms of symptom improvement, ostial patency, reduction of rhinosinusitis episodes, and very low surgical revision rates at 1-year follow-up.

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ACKNOWLEDGMENTS

All balloon devices used in the study (XprESS and FinESS) were manufactured by Entellus Medical, Inc. (Plymouth, MN). The REMODEL Principal Study Investigators include Michael Armstrong, M.D., Richmond ENT, Richmond, VA; Nadim Bikhazi, M.D., Ogden Clinic, Ogden, UT; Stephen Chandler, M.D., Montgomery Otolaryngology, Montgomery, AL; Jeffrey Cutler, M.D., Associates of Otolaryngology, Denver, CO; Aliya Ferouz-Colborn, M.D., San Diego Sleep and Sinus Clinic, San Diego, CA; James Gould, M.D., Synergy ENT Specialists, St. Louis, MO; Neeta Kohli-Dang, M.D., Huntsville Ear Nose and Throat PC, Huntsville, AL; Joshua Light, M.D., Ear, Nose and Throat Associates of South Florida, Boynton Beach, FL; Jeffrey Marvel, M.D., Marvel Clinic, Tullahoma, TN; C.T. Nguyen, M.D., Houston Sinus and Allergy, Houston, TX; J. Lewis Romett, M.D., CO ENT and Allergy, Colorado Springs, CO; Michael Schwartz, M.D., Ear, Nose and Throat Associates of South Florida, West Palm Beach, FL; Theodore Truitt, M.D., St. Cloud Ear, Nose and Throat, St. Cloud, MN; Manish Wani, M.D., TX Ear, Nose and Throat Specialist, P.A., Houston, TX.

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Standalone balloon dilation versus sinus surgery for chronic rhinosinusitis: a prospective, multicenter, randomized, controlled trial with 1-year follow-up.

The objective of this prospective, multicenter, randomized trial was to evaluate and compare 1-year outcomes from the REMODEL study between office bal...
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