Download Balloon dilation versus functional endoscopic

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
1738-183-rB
Study sponsored by Entellus Medical, Inc.
Acknowledgement
REMODEL Principal Study Investigators:
Michael Armstrong, MD
Nadim Bikhazi, MD
Stephen Chandler, MD
Aliya Ferouz-Colborn, MD
Jeffrey Cutler, MD
James Gould, MD
Joshua Light, MD
Jeffrey Marvel, MD
Michael Schwartz, MD
Theodore Truitt, MD
Richmond ENT
Ogden Clinic
Montgomery Otolaryngology
San Diego Sleep and Sinus Clinic
Colorado Sinus Institute
Synergy ENT Specialists
ENT Associates of South FL; Boynton
Beach
Marvel Clinic
ENT Associates of South FL; West
Palm Beach
St. Cloud Ear, Nose and Throat
Study sponsored by Entellus Medical, Inc.
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 LongTerm Follow-Up
Study sponsored by Entellus Medical, Inc.
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
Study sponsored by Entellus Medical, Inc.
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
Study sponsored by Entellus Medical, Inc.
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)
Study sponsored by Entellus Medical, Inc.
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
Study sponsored by Entellus Medical, Inc.
Study End Points
• Primary Endpoints
– Long-term symptom improvement:
• 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
Study sponsored by Entellus Medical, Inc.
Study End Points
• Secondary Endpoints
– Post-discharge recovery outcomes
– Short-term symptom improvement
• Combined one-week & one-month changes in
SNOT-20 scores
– Complication rate
• Serious device-related or procedure related
adverse event
– Revision rate
Study sponsored by Entellus Medical, Inc.
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 0.025
• 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
Study sponsored by Entellus Medical, Inc.
RESULTS
Study sponsored by Entellus Medical, Inc.
Participant Flow
105 patients underwent
randomization
2
withdrew
before
treatment
52 assigned to
balloon dilation
53 assigned to
FESS
50 received
balloon dilation
42 received
FESS
49 completed
6-month visit
42 completed
6-month visit
11
withdrew
before
treatment
Summary: 91/92 patients treated (99%) completed the
six-month follow-up
Study sponsored by Entellus Medical, Inc.
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
Study sponsored by Entellus Medical, Inc.
Baseline Demographics & Characteristics
Characteristic
Age (years)
Gender
Female
Ethnicity
Caucasian
Smoking History
Never smoked
Allergies
All year
Seasonal
Asthma/bronchitis
Previous Nasal Surgery
Septal Deviation
Lund-MacKay Score
Sinuses Affected
Maxillary only
Maxillary and anterior ethmoid
Chronic Rhinosinusitis Diagnosis
Chronic (> 12 weeks duration)
Recurrent acute (≥ 4 episodes in 1 yr)
# Sinusitis episodes past yr
Duration of Sinusitis (yrs)
Balloon Dilation
(n = 50)
Mean ± SD or n (%)
47.0 ± 14.6
Control (FESS)
(n = 42)
Mean ± SD or n (%)
47.9 ± 14.5
34 (68.0%)
23 (54.8%)
42 (84.0%)
36 (85.7%)
29 (58.0%)
27 (64.3%)
21 (42.0%)
13 (26.0%)
8 (16.0%)
7 (14.0%)
30 (60.0%)
3.2 ± 3.2
17 (40.5%)
12 (28.6%)
8 (19.0%)
8 (19.0%)
25 (59.5%)
3.6 ± 3.5
NS
31 (62.0%)
19 (38.0%)
26 (61.9%)
16 (38.1%)
NS
34 (68.0%)
16 (32.0%)
4.5 ± 1.8
12.4 ± 13.0
29 (69.0%)
13 (31.0%)
5.2 ± 2.8
12.7 ± 13.9
NS
p-value
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
Study sponsored by Entellus Medical, Inc.
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
Study sponsored by Entellus Medical, Inc.
Mean SNOT-20 Score
Problem
as bad as
it can be
No
problem
Primary Endpoint
Change in SNOT-20 Score
5
Balloon Dilation
Control (FESS)
4
p<0.001
3
2
Δ = -1.7
Δ = -1.6
1
0
Baseline
6 Months
Baseline
6 Months
Conclusion: Balloon dilation is not inferior to FESS for symptom
improvement
Study sponsored by Entellus Medical, Inc.
Primary Endpoint:
Debridements Per Study Arm
Mean /patient
1.2 ± 0.9
Total # of Debridements
Balloon Dilation
50
p<0.0001
Control (FESS)
40
30
20
Mean /patient
0.1 ± 0.6
10
0
Balloon Dilation
Control (FESS)
Conclusion: Balloon dilation is superior to FESS for postoperative
debridements
Study sponsored by Entellus Medical, Inc.
Debridement Details By Study Arm
100
90
92%
Balloon Dilation
Control (FESS)
Percent of Patients
80
70
55%
60
50
43%
40
30
26%
26%
14%
20
4%
10
0%
0
None
p<0.001
Removed
fibrin clots
Removed
scabs
2%
Cleared early
synechiae
0%
Removed
crusting
2%
5%
Cleared scar
tissue
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
Study sponsored by Entellus Medical, Inc.
Secondary Endpoint:
Procedure Recovery Outcomes
60
55%
Percentage of Patients
Balloon Dilation
50
Control (FESS)
40
28%
30
p=0.011
p=NS
20
10
17%
6%
0
Post-discharge nausea
Discharged with nasal bleeding
Conclusion: Post-op nasal bleeding significantly better for balloon
versus FESS
Study sponsored by Entellus Medical, Inc.
Secondary Endpoint:
Procedure Recovery Outcomes
Mean Number of Days
6
Balloon Dilation
p=0.002
Control (FESS)
4.8
5
p<0.001
4
2.8
3
2
1.6
p=NS
2.7
1.6
0.9
1
0
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
Study sponsored by Entellus Medical, Inc.
Secondary Endpoint:
Short Term SNOT-20 Scores
Control (FESS)
Balloon Dilation (BD)
FollowUp
Interval
n
Mean Change
± SD
n
Mean Change
± SD
1 Week
48
-1.5 +/-0.9
41
-1.0 ± 1.1
1 Month
49
-1.7 ± 1.0
40
-1.6 ± 1.0
Difference
BD-FESS p-value
(95% CI)
-0.3
(-0.5, -0.1)
0.014
Conclusion: Short-term symptom improvement is significantly
better for balloon dilation versus FESS
Study sponsored by Entellus Medical, Inc.
Secondary Endpoints
• Complications:
– No complications occurred in balloon dilation
arm or FESS arm
• Revision Surgeries:
– Balloon dilation: 2% (1 patient)
– FESS: 2.4% (1 patient)
Study sponsored by Entellus Medical, Inc.
Subgroup Analyses
Subgroup Analyses of Change in SNOT-20 Score at Six-months
Subgroup
Diseased Sinuses
Maxillary only
Maxillary & anterior ethmoid
Accessory Ostium
Yes
No
Septal Deviation
Yes
Balloon Dilation
Mean Change
n
± SD
Control (FESS)
Mean Change
n
± SD
30
18
-1.6 ± 1.1
-1.7 ± 1.0
25
16
-1.6 ± 1.0
-1.6 ± 0.9
NS
NS
17
-1.8 ± 1.4
9
-1.9 ± 0.6
NS
31
-1.6 ± 0.9
32
-1.5 ± 1.0
NS
28
-1.7 ± 1.2
24
-1.6 ± 1.0
NS
-1.7 ± 1.0
17
-1.7 ± 1.0
NS
-1.7 ± 1.1
28
-1.6 ± 1.0
NS
-1.6 ± 1,1
13
-1.6 ± 0.9
NS
No
20
Chronic Rhinosinusitis Diagnosis
32
Chronic (> 12 weeks duration)
Recurrent acute (≥ 4 episodes
16
in 1 year)
pvalue
Conclusion: Results are similar within and between study arms for all subgroups
Study sponsored by Entellus Medical, Inc.
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
Study sponsored by Entellus Medical, Inc.
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.
Study sponsored by Entellus Medical, Inc.
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.
Study sponsored by Entellus Medical, Inc.
Thank You
Study sponsored by Entellus Medical, Inc.
Additional Information
Study sponsored by Entellus Medical, Inc.
2007 Guideline
Definitions of CRS/RARS
Term
Definition
Chronic
Rhinosinusitis
(CRS)
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
Recurrent Acute
Rhinosinusitis
(RARS)
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)
Study sponsored by Entellus Medical, Inc.
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.
Study sponsored by Entellus Medical, Inc.
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.
Study sponsored by Entellus Medical, Inc.