Standalone balloon dilation versus sinus surgery for chronic rhinosinusitis: A prospective, multi-center, randomized, controlled trial

Transcription

1 Presented by Dr. Jeffrey Cutler at the Second Annual ARS Summer Sinus Symposium (July 19, 2013; Chicago, IL) Standalone balloon dilation versus sinus surgery for chronic rhinosinusitis: A prospective, multi-center, randomized, controlled trial rB

2 REMODEL Principal Study Investigators: Acknowledgement Michael Armstrong, MD Richmond ENT Nadim Bikhazi, MD Ogden Clinic Stephen Chandler, MD Montgomery Otolaryngology Aliya Ferouz-Colborn, MD San Diego Sleep and Sinus Clinic Jeffrey Cutler, MD Colorado Sinus Institute James Gould, MD Synergy ENT Specialists Joshua Light, MD ENT Associates of South FL; Boynton Beach Jeffrey Marvel, MD Marvel Clinic Michael Schwartz, MD ENT Associates of South FL; West Palm Beach Theodore Truitt, MD St. Cloud Ear, Nose and Throat

3 Background Many published studies of balloon dilation Case studies and single arm studies showing safety and efficacy Absence of adequately powered, prospective, multi-center, randomized control trials (RCT) comparing balloon dilation to FESS 2 published RCTs but not sufficiently powered First prospective study with sufficient statistical power to compare Balloon Dilation to FESS REMODEL: Randomized Evaluation of Maxillary Antrostomy Versus Ostial Dilation Efficacy Through Long- Term Follow-Up

4 Trial Design Study Design Prospective, multi-center, open-label, randomized controlled trial Treatment Balloon dilation of maxillary ostia & ethmoid infundibula in the clinic Control Maxillary antrostomy & uncinectomy with or without anterior ethmoidectomy Clinical Sites United States based Board Certified MDs in otolaryngology with experience in both balloon dilation and FESS

5 Trial Oversight An independent ENT physician blinded to treatment assignment reviewed: Postoperative debridement details Two independent ENT physicians audited: Completed study case report forms Data management processes & data accuracy Quality control measures Independent Statistician Generated randomization assignments stratified by sites to optimize balance at each site Calculated sample sizes and performed all statistical analyses

6 Study Population Inclusion Criteria Age 18 years Uncomplicated rhinosinusitis of the maxillary sinuses with or without anterior ethmoid disease Diagnosed with chronic or recurrent acute rhinosinusitis per the 2007 adult sinusitis clinical practice guidelines Met either the Anthem Coverage Guideline or BlueCross/BlueShield of North Carolina Corporate Medical Policy for medically necessary functional endoscopic sinus surgery (FESS)

7 Study Population Exclusion Criteria Evidence of posterior ethmoid, sphenoid or frontal sinusitis requiring FESS or balloon dilation Fungal disease Gross polypoid disease Require concurrent nasal surgery or have had previous sinus surgery Nasal surgery within 3 months prior to enrollment Severe septal deviation causing obstruction of the OMC Primary ciliary dysfunction Hemophilia Samter s Triad

8 Primary Endpoints Long-term symptom improvement: Study End Points Assessed by mean change in overall Sino-Nasal Outcome Test (SNOT-20) score between baseline and six-month follow-up Mean number of postoperative debridements Transnasal removal of dead, contaminated or adherent tissue or foreign material that may promote infection or impede healing throughout the study period

9 Secondary Endpoints Post-discharge recovery outcomes Short-term symptom improvement Study End Points Combined one-week & one-month changes in SNOT-20 scores Complication rate Serious device-related or procedure related adverse event Revision rate

10 Hypotheses & Sample Size Primary Endpoint Hypotheses 1. Long-term symptom improvement after balloon dilation is non-inferior to FESS 2. The number of postoperative debridements after balloon dilation is superior to FESS Sample Size Calculation Minimum of 36 patients in each arm to have 90% power to show non-inferiority of balloon dilation versus FESS for symptom improvement with one-sided alpha of Minimum of 23 patients in each arm to have 90% power to show superiority of balloon dilation verses FESS for debridements with one-sided alpha of 0.025

11 RESULTS

12 105 patients underwent randomization Participant Flow 2 withdrew before treatment 52 assigned to balloon dilation 50 received balloon dilation 53 assigned to FESS 42 received FESS 11 withdrew before treatment 49 completed 6-month visit 42 completed 6-month visit Summary: 91/92 patients treated (99%) completed the six-month follow-up

13 Withdrawn Patients Balloon Dilation Arm 2 withdrew before treatment 1 did not want to undergo in-office balloon dilation 1 needed cholecystectomy & didn t want to continue study FESS Arm 11 withdrew before treatment 8 did not want FESS 1 unable to comply with protocol follow-up requirements due to busy internship schedule 1 had severe, obstructive septal deviation 1 hospitalized with chest pain and MD did not want to treat under general anesthesia

14 Baseline Demographics & Characteristics Characteristic Balloon Dilation (n = 50) Control (FESS) (n = 42) p-value Mean ± SD or n (%) Mean ± SD or n (%) Age (years) 47.0 ± ± 14.5 NS Gender Female 34 (68.0%) 23 (54.8%) NS Ethnicity Caucasian 42 (84.0%) 36 (85.7%) NS Smoking History NS Never smoked 29 (58.0%) 27 (64.3%) Allergies All year 21 (42.0%) 17 (40.5%) NS Seasonal 13 (26.0%) 12 (28.6%) Asthma/bronchitis 8 (16.0%) 8 (19.0%) NS Previous Nasal Surgery 7 (14.0%) 8 (19.0%) NS Septal Deviation 30 (60.0%) 25 (59.5%) NS Lund-MacKay Score 3.2 ± ± 3.5 NS Sinuses Affected Maxillary only Maxillary and anterior ethmoid Chronic Rhinosinusitis Diagnosis Chronic (> 12 weeks duration) 31 (62.0%) 19 (38.0%) 26 (61.9%) 16 (38.1%) 34 (68.0%) 29 (69.0%) NS Recurrent acute ( 4 episodes in 1 yr) 16 (32.0%) 13 (31.0%) # Sinusitis episodes past yr 4.5 ± ± 2.8 NS Duration of Sinusitis (yrs) 12.4 ± ± 13.9 NS NS

15 Treatments Balloon Dilation (50 patients) 97 of 98 attempted dilations of the maxillary ostia and ethmoid infundibula were successfully completed for technical success rate of 99% 3 unilateral; 47 bilateral FESS (42 patients) 80 of 81 attempted maxillary antrostomies with uncinectomies were successfully completed for technical success rate of 99% 4 unilateral, 38 bilateral maxillary treatments 41 concomitant anterior ethmoidectomies (3 unilateral, 19 bilateral) were performed in 22 patients

16 Mean SNOT-20 Score Problem as bad as it can be 5 4 Primary Endpoint Change in SNOT-20 Score Balloon Dilation Control (FESS) 3 p< Δ = -1.7 Δ = No problem 0 Baseline 6 Months Baseline 6 Months Conclusion: Balloon dilation is not inferior to FESS for symptom improvement

17 Total # of Debridements Primary Endpoint: Debridements Per Study Arm Mean /patient 1.2 ± p< Mean /patient 0.1 ± 0.6 Balloon Dilation Control (FESS) 0 Balloon Dilation Control (FESS) Conclusion: Balloon dilation is superior to FESS for postoperative debridements

18 Percent of Patients Debridement Details By Study Arm % None 26% p< % 55% Removed fibrin clots 4% 43% Removed scabs 2% 26% Cleared early synechiae 0% Balloon Dilation Control (FESS) 14% Removed crusting Conclusion: Significantly more balloon patients (92%) did not require a debridement compared to FESS patients (26%) Note: Multiple maneuvers were often performed in a single debridement 2% 5% Cleared scar tissue

19 Percentage of Patients Secondary Endpoint: Procedure Recovery Outcomes Balloon Dilation Control (FESS) 55% p=ns 6% 17% 28% p= Post-discharge nausea Discharged with nasal bleeding Conclusion: Post-op nasal bleeding significantly better for balloon versus FESS

20 Mean Number of Days Secondary Endpoint: Procedure Recovery Outcomes 6 5 p= Balloon Dilation Control (FESS) 4 3 p< p=ns Recovery time Duration of Rx pain meds Duration of OTC pain meds Conclusion: Recovery time and duration of Rx pain medications significantly better for balloon versus FESS

21 Secondary Endpoint: Short Term SNOT-20 Scores Follow- Up Interval Balloon Dilation (BD) n Mean Change ± SD n Control (FESS) Mean Change ± SD Difference BD-FESS (95% CI) p-value 1 Week / ± Month ± ± (-0.5, -0.1) Conclusion: Short-term symptom improvement is significantly better for balloon dilation versus FESS

22 Complications: Secondary Endpoints No complications occurred in balloon dilation arm or FESS arm Revision Surgeries: Balloon dilation: 2% (1 patient) FESS: 2.4% (1 patient)

23 Subgroup Balloon Dilation Mean Change ± SD n Subgroup Analyses Subgroup Analyses of Change in SNOT-20 Score at Six-months n Control (FESS) Mean Change ± SD p- value Diseased Sinuses Maxillary only ± ± 1.0 NS Maxillary & anterior ethmoid ± ± 0.9 NS Accessory Ostium Yes ± ± 0.6 NS No ± ± 1.0 NS Septal Deviation Yes ± ± 1.0 NS No ± ± 1.0 NS Chronic Rhinosinusitis Diagnosis Chronic (> 12 weeks duration) ± ± 1.0 NS Recurrent acute ( 4 episodes in 1 year) ± 1, ± 0.9 NS Conclusion: Results are similar within and between study arms for all subgroups

24 Study Limitations Patients were not blinded to treatment Would have required all procedures to be conducted under general anesthesia, eliminating the possibility of studying one of the benefits of office balloon dilation Physicians were not blinded to treatment Post-procedure sinus medication usage was not controlled

25 Summary This is the first prospective, multi-center, randomized controlled trial with sufficient statistical power to compare sinus ostial balloon dilation to FESS for the treatment of medically refractory chronic rhinosinusitis. No differences between study arms in baseline demographics, co-morbidities, disease severity, or QOL scores. 99% follow up (91/92 patients) at 6 months. These data provide a sound basis for assessing outcome differences between FESS and balloon dilation in this population.

26 Conclusions Adult patients with maxillary/anterior ethmoid disease with uncomplicated chronic rhinosinusitis who fail medical management and meet criteria for FESS experience symptom improvement following balloon dilation that is non-inferior to the improvement also occurring after FESS. Balloon dilation results in fewer postoperative debridements than FESS, demonstrating superiority of the balloon arm. Both treatments are safe as neither arm produced any serious adverse events and the durability of each has been established through very low reported rates of revision surgery.

27 Thank You

28 Additional Information

29 2007 Guideline Definitions of CRS/RARS Term Chronic Rhinosinusitis (CRS) Recurrent Acute Rhinosinusitis (RARS) Definition Twelve weeks or longer of two or more of the following symptoms: Mucopurulent drainage Nasal congestion/obstruction Facial pain/pressure/ fullness Decreased sense of smell AND inflammation is documented by one of the following: Purulent mucous or edema of the middle meatus or ethmoid region Radiographic imaging showing inflammation of the paranasal sinuses Four or more episodes per year of ABRS without signs or symptoms of rhinosinusitis between episodes. Symptoms or signs are present 10 days or more beyond the onset of upper respiratory symptoms or Symptoms or signs worsen within 10 days after an initial improvement (double worsening)

30 Policies for Medically Necessary FESS: BlueCross BlueShield of N. Carolina (August 2011) Uncomplicated sinusitis and all of the following: Either four or more documented episodes of acute rhinosinusitis in one year, or chronic sinusitis that interferes with lifestyle; and Optimal medical therapy has been attempted and failed, as indicated by all of the following: Allergic evaluation and treatment when indicated, Decongestants when indicated, Topical and/or systemic steroids when indicated, Treatment of rhinitis medicamentosa, when present, Education on environmental irritants including tobacco smoke, Antibiotic therapy consisting of 3 consecutive weeks of appropriate antibiotic drugs, or multiple 2 to 3 week courses of appropriate antibiotic drugs during the symptomatic periods. For chronic rhinosinusitis, documentation of coronal CT and/or nasal endoscopy following optimal medical therapy showing persistent sinus pathology. For recurrent acute rhinosinusitis, coronal CT and nasal endoscopy may be normal after treatment. However, CT and/or nasal endoscopy during acute rhinosinusitis should document sinus pathology amenable to surgical treatment.

31 Policies for Medically Necessary FESS: Anthem (CG-SURG-24; December 2011) Uncomplicated sinusitis confined to the paranasal sinuses without adjacent involvement of neurologic, soft tissue, or bony structures and all of the following: Either four or more documented episodes of acute rhinosinusitis (i.e., less than 4 weeks duration) in one year, or chronic sinusitis (i.e., greater than 12 weeks duration) that interferes with lifestyle; and Maximal medical therapy has been attempted, as indicated by all of the following: Antibiotic therapy for at least 4 weeks; and Trial of inhaled steroids; and Nasal lavage Allergy assessment.