Chronic Sinusitis, Nasal Polyps
Conditions
Keywords
corticosteroid-eluting sinus implant, chronic rhinosinusitis, mometasone furoate, polyposis
Brief summary
The RESOLVE Study is a randomized controlled trial with the S8 Sinus Implant in 100 chronic sinusitis patients with recurrent nasal polyps.
Detailed description
RESOLVE is a randomized (1:1), sham-controlled, parallel group, double-blind multicenter study in 100 chronic sinusitis patients who had prior endoscopic sinus surgery and presented with recurrent nasal polyps. The objective of the study was to assess the safety and efficacy of the S8 Sinus Implant, a steroid-eluting sinus implant, consisting of a bioabsorbable self-expanding sinus implant coated with 1350 mcg of mometasone furoate (MF) and a single-use delivery system. Implant is placed in-office in the ethmoid sinus under local anesthesia. The coating on the S8 implant provides controlled release of MF to the sinus mucosa over 90 days, with the majority of drug released within 60 days.
Interventions
DRUGS8 Sinus Implant
In-office bilateral placement of the S8 Sinus Implant (mometasone furoate, 1350 mcg) in the ethmoid sinuses
PROCEDURESham procedure
In-office bilateral sham procedure
DRUGMometasone furoate nasal spray
Two sprays in each nostril once daily, totaling 200 mcg of mometasone furoate throughout Day 90
Sponsors
Intersect ENT
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Participants were blindfolded and earmuffed during the baseline procedure and follow-up endoscopic examinations. Implants were removed at Day 60 to allow blinded assessment of bilateral polyp grade at Day 90 by a centralized videoendoscopy review by a panel of 3 independent sinus surgeons.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Candidates for this study had to meet ALL of the following inclusion criteria: 1\. General Inclusion Criteria 1. Patient has provided written informed consent using a form approved by the reviewing IRB. 2. Patient is ≥ 18 years of age. 3. Patient is willing and able to comply with protocol requirements. 4. Patient has a previous confirmed diagnosis of CS defined as inflammation of the mucosa of the paranasal sinuses. 5. Patient has undergone bilateral total ethmoidectomy (must be at least 90 day beyond the date of last sinus surgery). 6. Patient has recurrent bilateral sinus obstruction due to polyposis (Grades 1 through 3 only). 7. Patient must have a Grade 2 polyposis on at least 1 ethmoid side. 8. Patient is able to tolerate the use of Nasonex topical intranasal steroid spray once daily. 9. Patient is indicated for a repeat ESS per the study definition. Patient must have: (i) a minimum symptom burden on the SNOT 22, consisting of a minimum score of 2 on at least 2 of the 5 hallmark symptoms of CS (nasal blockage, post-nasal discharge, thick nasal discharge, facial pain/pressure, and decreased sense of smell); (ii) persistent symptoms of CS despite ongoing treatment with topical intranasal steroid irrigations or sprays at least once daily for at least 2 weeks preceding enrollment; (iii) had treatment with a high-dose form of steroids (e.g., oral, parenteral, injection into polyps) and/or sinus steroid irrigations within the preceding 2 years, or refused such therapy due to intolerance/side effects; (iv) a known history of repeated courses of treatment with aggressive steroid therapy for recurrent sinusitis; and (v) endoscopic evidence of polyp recurrence, scarring, and/or obstructive mucosal edema. 10. Patient is able to tolerate use of topical/local anesthesia and the implant procedure in an office or clinic setting. 11. In the opinion of the physician, treatment with S8 Sinus Implant or sham procedure is technically feasible (able to pass 5-9 mm device into middle meatus) bilaterally. 12. Female patients of child-bearing potential must not be pregnant and must agree to not become pregnant during the course of the study. 13. Female patients of child-bearing potential must agree to use consistent and acceptable method/s of birth control during the course of the study.
Exclusion criteria
Candidates were excluded if they met ANY of the following criteria: General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nasal Obstruction/Congestion Score | 90 days | Nasal Obstruction by patients using a paper questionnaire on a scale from 0 (no problem) to 5 (problem as bad as it can be). Negative values for change from baseline represented reduction (improvement) in |
| Bilateral Polyp Grade | 90 days | Polyp grade was determined by a panel of 3 independent sinus surgeons based on a centralized, blinded videoendoscopy review. Each sinus was graded from 0 (no visible polyps) to 4 (nasal polyps completely obstructing nasal cavity) and then the left and right values were added to obtain a total bilateral polyp grade, ranging from 0 to 8. Negative values for change from baseline represented reduction (improvement) in bilateral polyp grade. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ethmoid Sinus Obstruction | 90 days | Percentage of the ethmoid sinus volume obstructed by scarring, polyps, or edema on endoscopy, as determined by a panel of 3 independent sinus surgeons based on a centralized, blinded videoendoscopy review using a 100-mm visual analogue scale (VAS), ranging from 0 (absence of obstruction) to 100 (complete obstruction). Negative values for change from baseline represented reduction (improvement) in ethmoid sinus obstruction. |
| Bilateral Polyp Grade | 90 days, 6 months | Polyps were graded by clinical investigators on a scale from 0 (no visible polyps) to 4 (nasal polyps completely obstructing nasal cavity) and then the left and right values were added to obtain a total bilateral polyp grade, ranging from 0 to 8. Negative values for change from baseline indicate reduction (improvement) in nasal polyps. |
| Nasal Obstruction Symptom Evaluation (NOSE) Score | 6 months | NOSE scale is a validated symptom scoring instrument consisting of 5 questions each scored by patients on a 5-point Likert scale from 0 (not a problem) to 4 (severe problem), then multiplied by 5 and resulting in a total score ranging from 0 to 100. Negative values for change from baseline represented reduction (improvement) in NOSE score. |
| Percentage of Patients Indicated for Revision Endoscopic Sinus Surgery (RESS) | 90 days, 6 months | To be indicated for RESS, the following criteria had to be met: * Continued to use topical intranasal steroids daily; * Continued to complain of at least 2 symptoms of chronic sinusitis despite ongoing topical intranasal steroid use * Needed or had received at least 1 course of aggressive steroid therapy or had refused such therapy due to intolerance/side effects; and * Had endoscopic evidence of persisting ethmoid sinus obstruction (bilateral polyp grade \>=2 on at least one side) |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled between January 2013 and November 2013 at 18 clinical sites (12 private, 6 academic).
Pre-assignment details
A total of 100 patients were enrolled and randomized. met final eligibility. There was a 2-week run-in period before screening during which participants were required to use an intranasal corticosteroid spray.
Participants by arm
| Arm | Count |
|---|---|
| Treatment In-office bilateral placement of the S8 Sinus Implant (mometasone furoate, 1350 mcg) in the ethmoid sinuses
Mometasone furoate nasal spray (200mcg) once daily | 53 |
| Control In-office bilateral sham procedure
Mometasone furoate nasal spray (200mcg) once daily | 47 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Treatment | Total | Control |
|---|---|---|---|
| Age, Continuous | 47.8 years STANDARD_DEVIATION 12.61 | 49.6 years STANDARD_DEVIATION 12.93 | 51.6 years STANDARD_DEVIATION 13.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 95 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 8 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 47 Participants | 91 Participants | 44 Participants |
| Region of Enrollment United States | 53 Participants | 100 Participants | 47 Participants |
| Sex: Female, Male Female | 24 Participants | 40 Participants | 16 Participants |
| Sex: Female, Male Male | 29 Participants | 60 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 47 |
| other Total, other adverse events | 38 / 53 | 36 / 47 |
| serious Total, serious adverse events | 0 / 53 | 1 / 47 |
Outcome results
Primary
Bilateral Polyp Grade
Polyp grade was determined by a panel of 3 independent sinus surgeons based on a centralized, blinded videoendoscopy review. Each sinus was graded from 0 (no visible polyps) to 4 (nasal polyps completely obstructing nasal cavity) and then the left and right values were added to obtain a total bilateral polyp grade, ranging from 0 to 8. Negative values for change from baseline represented reduction (improvement) in bilateral polyp grade.
Time frame: 90 days
Population: Intent-to-treat population. Values were adjusted for steroid and surgical interventions by LOCF approach. There were 2 (2%) participants (2 treatment, 0 control) with missing values. No imputation of missing values was performed. Negative values for change from baseline represent improvement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Bilateral Polyp Grade | Baseline | 4.90 units on a scale | Standard Deviation 0.918 |
| Treatment | Bilateral Polyp Grade | Day 90 | 4.12 units on a scale | Standard Deviation 1.162 |
| Treatment | Bilateral Polyp Grade | Change from baseline | -0.76 units on a scale | Standard Deviation 0.875 |
| Control | Bilateral Polyp Grade | Baseline | 4.39 units on a scale | Standard Deviation 1.448 |
| Control | Bilateral Polyp Grade | Day 90 | 4.00 units on a scale | Standard Deviation 1.72 |
| Control | Bilateral Polyp Grade | Change from baseline | -0.38 units on a scale | Standard Deviation 0.998 |
p-value: 0.0985ANCOVA
Comparison: Bilateral polyp grade change in a subset of 67 patients with higher polyp burden at baseline (grade 2 or higher on each side confirmed by the independent panel)p-value: 0.049ANOVA
Primary
Nasal Obstruction/Congestion Score
Nasal Obstruction by patients using a paper questionnaire on a scale from 0 (no problem) to 5 (problem as bad as it can be). Negative values for change from baseline represented reduction (improvement) in
Time frame: 90 days
Population: Intent-to-treat population. Values were adjusted for steroid and surgical interventions by LOCF approach. There were 3 (3%) participants (1 treatment, 2 control) with missing values at Day 90. No imputation of missing values was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Nasal Obstruction/Congestion Score | Baseline | 3.62 units on a scale | Standard Deviation 1.18 |
| Treatment | Nasal Obstruction/Congestion Score | Day 90 | 2.31 units on a scale | Standard Deviation 1.422 |
| Treatment | Nasal Obstruction/Congestion Score | Change from baseline | -1.33 units on a scale | Standard Deviation 1.465 |
| Control | Nasal Obstruction/Congestion Score | Baseline | 3.30 units on a scale | Standard Deviation 1.159 |
| Control | Nasal Obstruction/Congestion Score | Day 90 | 2.62 units on a scale | Standard Deviation 1.336 |
| Control | Nasal Obstruction/Congestion Score | Change from baseline | -0.67 units on a scale | Standard Deviation 1.446 |
p-value: 0.1365ANCOVA
Comparison: The change from baseline to Day 90 in Nasal Obstruction/Congestion score in the subset of participants with higher polyp burden at baseline (grade 2 or higher polyps on each side; N=67).p-value: 0.0505ANCOVA
Secondary
Bilateral Polyp Grade
Polyps were graded by clinical investigators on a scale from 0 (no visible polyps) to 4 (nasal polyps completely obstructing nasal cavity) and then the left and right values were added to obtain a total bilateral polyp grade, ranging from 0 to 8. Negative values for change from baseline indicate reduction (improvement) in nasal polyps.
Time frame: 90 days, 6 months
Population: Intent-to-treat population. Values were adjusted for steroid and surgical interventions by LOCF approach. There were 3 (3.0%) participants (1 treatment, 2 control) with missing values at 90 days and 4 (4.0%) participants (2 treatment, 2 control) with missing values at Month 6. No imputation of missing values was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Bilateral Polyp Grade | 90 days | 3.65 units on a scale | Standard Error 1.655 |
| Treatment | Bilateral Polyp Grade | Month 6 | 3.96 units on a scale | Standard Error 1.587 |
| Treatment | Bilateral Polyp Grade | Change from baseline to 90 days | -1.04 units on a scale | Standard Error 1.68 |
| Treatment | Bilateral Polyp Grade | Change from baseline to 6 months | -0.71 units on a scale | Standard Error 1.527 |
| Treatment | Bilateral Polyp Grade | Baseline | 4.68 units on a scale | Standard Error 0.956 |
| Control | Bilateral Polyp Grade | Change from baseline to 6 months | 0.02 units on a scale | Standard Error 1.158 |
| Control | Bilateral Polyp Grade | Baseline | 4.32 units on a scale | Standard Error 1.105 |
| Control | Bilateral Polyp Grade | 90 days | 4.24 units on a scale | Standard Error 1.667 |
| Control | Bilateral Polyp Grade | Change from baseline to 90 days | -0.09 units on a scale | Standard Error 1.203 |
| Control | Bilateral Polyp Grade | Month 6 | 4.36 units on a scale | Standard Error 1.708 |
p-value: 0.0162ANCOVA
p-value: 0.0175ANCOVA
Secondary
Ethmoid Sinus Obstruction
Percentage of the ethmoid sinus volume obstructed by scarring, polyps, or edema on endoscopy, as determined by a panel of 3 independent sinus surgeons based on a centralized, blinded videoendoscopy review using a 100-mm visual analogue scale (VAS), ranging from 0 (absence of obstruction) to 100 (complete obstruction). Negative values for change from baseline represented reduction (improvement) in ethmoid sinus obstruction.
Time frame: 90 days
Population: Intent-to-treat population. Values were adjusted for steroid and surgical interventions by LOCF approach. There was1 (1.0%) participant (treatment) with missing values at baseline and Day 90. No imputation of missing values was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Ethmoid Sinus Obstruction | Baseline | 70.59 units on a scale | Standard Deviation 18.201 |
| Treatment | Ethmoid Sinus Obstruction | Day 90 | 53.54 units on a scale | Standard Deviation 20.14 |
| Treatment | Ethmoid Sinus Obstruction | Change from baseline | -17.05 units on a scale | Standard Deviation 19.361 |
| Control | Ethmoid Sinus Obstruction | Change from baseline | -5.57 units on a scale | Standard Deviation 18.279 |
| Control | Ethmoid Sinus Obstruction | Baseline | 62.74 units on a scale | Standard Deviation 25.673 |
| Control | Ethmoid Sinus Obstruction | Day 90 | 57.17 units on a scale | Standard Deviation 28.516 |
p-value: 0.0099ANCOVA
Secondary
Nasal Obstruction Symptom Evaluation (NOSE) Score
NOSE scale is a validated symptom scoring instrument consisting of 5 questions each scored by patients on a 5-point Likert scale from 0 (not a problem) to 4 (severe problem), then multiplied by 5 and resulting in a total score ranging from 0 to 100. Negative values for change from baseline represented reduction (improvement) in NOSE score.
Time frame: 6 months
Population: Intent-to-treat population. Values were adjusted for steroid and surgical interventions by LOCF approach. There were 3 (3.0%) participants (1 treatment, 2 control) with missing values at Month 6. No imputation of missing values was performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Nasal Obstruction Symptom Evaluation (NOSE) Score | Baseline | 66.79 units on a scale | Standard Deviation 26.658 |
| Treatment | Nasal Obstruction Symptom Evaluation (NOSE) Score | Month 6 | 41.83 units on a scale | Standard Deviation 24.395 |
| Treatment | Nasal Obstruction Symptom Evaluation (NOSE) Score | Change from baseline | -25.58 units on a scale | Standard Deviation 28.174 |
| Control | Nasal Obstruction Symptom Evaluation (NOSE) Score | Baseline | 63.19 units on a scale | Standard Deviation 23.943 |
| Control | Nasal Obstruction Symptom Evaluation (NOSE) Score | Month 6 | 50.67 units on a scale | Standard Deviation 25.597 |
| Control | Nasal Obstruction Symptom Evaluation (NOSE) Score | Change from baseline | -12.22 units on a scale | Standard Deviation 23.874 |
p-value: 0.0209ANCOVA
Secondary
Percentage of Patients Indicated for Revision Endoscopic Sinus Surgery (RESS)
To be indicated for RESS, the following criteria had to be met: * Continued to use topical intranasal steroids daily; * Continued to complain of at least 2 symptoms of chronic sinusitis despite ongoing topical intranasal steroid use * Needed or had received at least 1 course of aggressive steroid therapy or had refused such therapy due to intolerance/side effects; and * Had endoscopic evidence of persisting ethmoid sinus obstruction (bilateral polyp grade \>=2 on at least one side)
Time frame: 90 days, 6 months
Population: Intent-to-treat population consisted of all patients in whom an implant or sham procedure was attempted. There were 2 (2.0%) participants (1 treatment, 1 control) who withdrew from the study prior to Day 90. No imputation of missing values was performed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Percentage of Patients Indicated for Revision Endoscopic Sinus Surgery (RESS) | Baseline | 53 Participants |
| Treatment | Percentage of Patients Indicated for Revision Endoscopic Sinus Surgery (RESS) | Day 90 | 25 Participants |
| Treatment | Percentage of Patients Indicated for Revision Endoscopic Sinus Surgery (RESS) | Month 6 | 36 Participants |
| Control | Percentage of Patients Indicated for Revision Endoscopic Sinus Surgery (RESS) | Baseline | 47 Participants |
| Control | Percentage of Patients Indicated for Revision Endoscopic Sinus Surgery (RESS) | Day 90 | 36 Participants |
| Control | Percentage of Patients Indicated for Revision Endoscopic Sinus Surgery (RESS) | Month 6 | 41 Participants |