Chronic Rhinosinusitis (Diagnosis)
Conditions
Brief summary
The objective of the ASCEND Study is to assess the safety, performance, and efficacy of the Intersect ENT UP Drug-Coated Device when used in chronic rhinosinusitis (CRS) patients undergoing balloon dilation of frontal sinus ostia (FSO)
Detailed description
This is a prospective, multicenter study enrolling two consecutive cohorts: PK cohort (N=5): A non-randomized cohort to assess the systemic safety and performance of the UP Drug-Coated Device for in-office bilateral dilation of the FSO (2 inflations in each FSO for a total of 4 inflations per device). Subsequently, the UP Drug-Coated Device may be used to dilate any sphenoid or maxillary sinuses. Randomized cohort (N=70): A randomized, intra-patient controlled, double-blind cohort of 70 subjects to assess the safety and efficacy of the UP Drug-Coated Device used for in-office dilation of the FSO. The FSO randomized to the treatment (Treatment) will undergo dilation using the UP Drug-Coated Device (2 inflations per device) while the contralateral FSO (Control) will be dilated with a UP Control Device (2 inflations per device).
Interventions
DEVICEDrug-Coated Device
3000 mcg mometasone furoate-coated sinus dilation device
DEVICEControl Device
Sinus dilation device without drug
Sponsors
Intersect ENT
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The randomized cohort is double-blinded, which both participants and outcome assessor being masked to treatment assignment
Intervention model description
A PK non-randomized cohort in 5 participants, followed by a randomized, intra-patient controlled double-blind cohort in 70 participants
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Confirmed diagnosis of CRS per the 2016, International Consensus Statement on Allergy and Rhinology definition. 2. Bilateral disease in the frontal sinuses (Lund-Mackay score ≥ 1 on each side) on CT scan within 30 days prior to enrollment in the PK cohort and prior to randomization in the randomized cohort. 3. Patient has bilateral obstruction of the frontal recess/FSO due to scarring and/or polypoid edema confirmed on endoscopy (patency grade of 0 or 1 for each FSO). 4. Balloon dilation of the FSO judged to be feasible and medically appropriate. 5. Patient has had prior ESS (\> 30 days with a healed mucosa) including bilateral ethmoidectomy (anterior or total) and uncinectomy for better visualization of the FSO. 6. Balloon dilation of the FSO with a 6 mm balloon is judged to be feasible (use light-assisted or image-guided instrument such as a frontal sinus seeker tip to confirm access of each FSO) and medically appropriate.
Exclusion criteria
1. Expanded amount of ethmoid polyposis (grade \> 2 PK cohort, grade ≥ 2 randomized cohort). 2. Complications from prior ESS or balloon dilation procedure (e.g., cerebrospinal fluid leak or injury to the skull base). 3. History of aspirin exacerbated respiratory disease (AERD). 4. Current smokers. 5. History of allergy or intolerance to mometasone furoate. 6. Oral-steroid dependent condition. 7. Evidence of acute rhinosinusitis, invasive fungal sinusitis or another disease or condition expected to compromise survival or ability to complete assessments during the 30-day follow-up period in the PK cohort and druing the 60-day follow-up period in the randomized cohort. 8. Use of parenteral and injected steroids (e.g., Kenalog) 30 days prior to the baseline procedure. 9. Use of oral steroids, budesonide or other sinus steroid irrigations/rinses or drops, nebulized steroids administered nasally 14 days prior to screening in the PK cohort and prior to baseline in the randomized cohort. 10. Glaucoma or posterior subcapsular cataract.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Randomized Cohort: Difference in Patency Grade of FSO | 30 days | Difference in the patency grade of the FSO between treatment sides at Day 30, as determined by an independent, blinded sinus surgeon based on the centralized video-endoscopy review. Patency of the FSO assessed endoscopically by probing with a 3-mm olive-shaped frontal sinus suction tip (suction tip) and graded on a 5-point scale as follows - 0: Occluded (no opening visible); 1: Significantly stenosed (not occluded, but unable to pass the 3-mm suction tip); 2: Moderately stenosed (able to easily pass the 3-mm suction tip with no additional space around it); 3: Minimally stenosed (able to easily pass the 3-mm suction tip with additional 1-2 mm space around it); 4: Completely patent (able to easily pass the 3-mm suction tip with additional \>2 mm space around it) |
| The Number of Participants in the PK Cohort With Successful Dilation of Attempted FSO at Baseline | Baseline | Successful dilation of attempted FSO using the Drug-Coated Device with no unanticipated serious adverse device effects. A successful dilation of the FSO is defined as insertion of the UP Drug-Coated Device into the targeted FSO followed by 2 consecutive, complete inflations of the balloon. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Randomized Cohort: Estimated Frontal Sinus Ostia (FSO) Diameter | 30 days | The smallest and largest diameters of the FSO determined by an independent, blinded sinus surgeon based on the centralized video-endoscopy review. FSO diameter estimated endoscopically by probing with a 3-mm olive-shaped frontal sinus suction tip and reported in mm. |
| PK Cohort: Estimated Largest Frontal Sinus Ostia (FSO) Diameter | Baseline to 30 days | The smallest and largest diameters of the FSO are estimated endoscopically by probing with a 3-mm olive-shaped frontal sinus suction tip and reported in mm. |
| PK Cohort: Estimated Smallest Frontal Sinus Ostia (FSO) Diameter | Baseline to 30 days | The smallest and largest diameters of the FSO are estimated endoscopically by probing with a 3-mm olive-shaped frontal sinus suction tip and reported in mm. |
| PK Cohort: Total Sino-Nasal Outcomes Test Score (SNOT-22) | Baseline, Day 14 and Day 30 | SNOT-22 is a validated, disease-specific, symptom-scoring instrument consisting of 22 questions, each scored by patient on a 6-point scale as follows: 0: No problem; 1: Very mild problem; 2: Mild or slight problem; 3: Moderate problem; 4: Severe problem; 5: Problem as bad as it can be. Sum of all 22 questions constitutes the total SNOT-22 score with a maximum total score equal to 110. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Randomized Cohort Randomized cohort (n=70) used a randomized intra-patient desgin which received Drug-Coated Device to dilate randomized frontal sinus ostium and control device in the randomized contralateral frontal sinus ostium.
Drug-Coated Device: 3000 mcg mometasone furoate-coated sinus dilation device. Control Device: Sinus dilation device without drug. | 70 |
| PK Cohort- Safety PK cohort (n=5) used a non-randomized design in which one Drug-Coated Device was used to dilate both frontal sinus ostia.
Drug-Coated Device: 3000 mcg mometasone furoate-coated sinus dilation device. | 5 |
| Total | 75 |
Baseline characteristics
| Characteristic | Randomized Cohort | PK Cohort- Safety | Total |
|---|---|---|---|
| Age, Continuous | 54.9 years STANDARD_DEVIATION 11.37 | 61.2 years STANDARD_DEVIATION 10.94 | 54.9 years STANDARD_DEVIATION 11.3 |
| CT Lund Mackay Score - Total | 8.6 Units on a scale STANDARD_DEVIATION 2.94 | 11.0 Units on a scale STANDARD_DEVIATION 2.92 | 9.8 Units on a scale STANDARD_DEVIATION 2.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 66 Participants | 5 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| History of Allergic Rhinitis No | 9 Participants | 1 Participants | 10 Participants |
| History of Allergic Rhinitis Yes | 61 Participants | 4 Participants | 65 Participants |
| History of Aspirin Intolerance or Allergy No | 68 Participants | 4 Participants | 72 Participants |
| History of Aspirin Intolerance or Allergy Yes | 2 Participants | 1 Participants | 3 Participants |
| History of Asthma No | 37 Participants | 4 Participants | 41 Participants |
| History of Asthma Yes | 33 Participants | 1 Participants | 34 Participants |
| History of Repeated Courses of Corticosteroids No | 35 Participants | 3 Participants | 38 Participants |
| History of Repeated Courses of Corticosteroids Yes | 35 Participants | 2 Participants | 37 Participants |
| Number of Prior Endoscopic Sinus Surgery 1 | 32 Participants | 1 Participants | 33 Participants |
| Number of Prior Endoscopic Sinus Surgery 2 | 20 Participants | 2 Participants | 22 Participants |
| Number of Prior Endoscopic Sinus Surgery 3 | 10 Participants | 0 Participants | 10 Participants |
| Number of Prior Endoscopic Sinus Surgery 4 or more | 8 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 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 | 64 Participants | 4 Participants | 68 Participants |
| Sex: Female, Male Female | 26 Participants | 1 Participants | 27 Participants |
| Sex: Female, Male Male | 44 Participants | 4 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 5 |
| other Total, other adverse events | 11 / 70 | 2 / 5 |
| serious Total, serious adverse events | 1 / 70 | 0 / 5 |
Outcome results
Primary
Randomized Cohort: Difference in Patency Grade of FSO
Difference in the patency grade of the FSO between treatment sides at Day 30, as determined by an independent, blinded sinus surgeon based on the centralized video-endoscopy review. Patency of the FSO assessed endoscopically by probing with a 3-mm olive-shaped frontal sinus suction tip (suction tip) and graded on a 5-point scale as follows - 0: Occluded (no opening visible); 1: Significantly stenosed (not occluded, but unable to pass the 3-mm suction tip); 2: Moderately stenosed (able to easily pass the 3-mm suction tip with no additional space around it); 3: Minimally stenosed (able to easily pass the 3-mm suction tip with additional 1-2 mm space around it); 4: Completely patent (able to easily pass the 3-mm suction tip with additional \>2 mm space around it)
Time frame: 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized Cohort - Treatment Arm | Randomized Cohort: Difference in Patency Grade of FSO | 1.6 score on a scale | Standard Deviation 1 |
| Randomized Cohort - Control Arm | Randomized Cohort: Difference in Patency Grade of FSO | 1.5 score on a scale | Standard Deviation 1.07 |
Primary
The Number of Participants in the PK Cohort With Successful Dilation of Attempted FSO at Baseline
Successful dilation of attempted FSO using the Drug-Coated Device with no unanticipated serious adverse device effects. A successful dilation of the FSO is defined as insertion of the UP Drug-Coated Device into the targeted FSO followed by 2 consecutive, complete inflations of the balloon.
Time frame: Baseline
Population: 'Analysis per patient.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Randomized Cohort - Treatment Arm | The Number of Participants in the PK Cohort With Successful Dilation of Attempted FSO at Baseline | 10 frontal sinus ostia |
Secondary
PK Cohort: Estimated Largest Frontal Sinus Ostia (FSO) Diameter
The smallest and largest diameters of the FSO are estimated endoscopically by probing with a 3-mm olive-shaped frontal sinus suction tip and reported in mm.
Time frame: Baseline to 30 days
Population: Analysis per patient.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Cohort - Treatment Arm | PK Cohort: Estimated Largest Frontal Sinus Ostia (FSO) Diameter | Day 7 | 4.1 mm | Standard Deviation 2.02 |
| Randomized Cohort - Treatment Arm | PK Cohort: Estimated Largest Frontal Sinus Ostia (FSO) Diameter | Baseline pre-dilation | 1.2 mm | Standard Deviation 0.92 |
| Randomized Cohort - Treatment Arm | PK Cohort: Estimated Largest Frontal Sinus Ostia (FSO) Diameter | Baseline post-dilation | 3.3 mm | Standard Deviation 2.31 |
| Randomized Cohort - Treatment Arm | PK Cohort: Estimated Largest Frontal Sinus Ostia (FSO) Diameter | Day 14 | 3.3 mm | Standard Deviation 2 |
| Randomized Cohort - Treatment Arm | PK Cohort: Estimated Largest Frontal Sinus Ostia (FSO) Diameter | Day 21 | 2.4 mm | Standard Deviation 2.22 |
| Randomized Cohort - Treatment Arm | PK Cohort: Estimated Largest Frontal Sinus Ostia (FSO) Diameter | Day 30 | 2.6 mm | Standard Deviation 2.12 |
Secondary
PK Cohort: Estimated Smallest Frontal Sinus Ostia (FSO) Diameter
The smallest and largest diameters of the FSO are estimated endoscopically by probing with a 3-mm olive-shaped frontal sinus suction tip and reported in mm.
Time frame: Baseline to 30 days
Population: Analysis per patient.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Cohort - Treatment Arm | PK Cohort: Estimated Smallest Frontal Sinus Ostia (FSO) Diameter | Baseline pre-dilation | 1.1 mm | Standard Deviation 0.88 |
| Randomized Cohort - Treatment Arm | PK Cohort: Estimated Smallest Frontal Sinus Ostia (FSO) Diameter | Baseline post-dilation | 2.9 mm | Standard Deviation 1.85 |
| Randomized Cohort - Treatment Arm | PK Cohort: Estimated Smallest Frontal Sinus Ostia (FSO) Diameter | Day 7 | 3.2 mm | Standard Deviation 1.75 |
| Randomized Cohort - Treatment Arm | PK Cohort: Estimated Smallest Frontal Sinus Ostia (FSO) Diameter | Day 14 | 3.1 mm | Standard Deviation 1.91 |
| Randomized Cohort - Treatment Arm | PK Cohort: Estimated Smallest Frontal Sinus Ostia (FSO) Diameter | Day 21 | 2.1 mm | Standard Deviation 1.97 |
| Randomized Cohort - Treatment Arm | PK Cohort: Estimated Smallest Frontal Sinus Ostia (FSO) Diameter | Day 30 | 2.2 mm | Standard Deviation 1.81 |
Secondary
PK Cohort: Total Sino-Nasal Outcomes Test Score (SNOT-22)
SNOT-22 is a validated, disease-specific, symptom-scoring instrument consisting of 22 questions, each scored by patient on a 6-point scale as follows: 0: No problem; 1: Very mild problem; 2: Mild or slight problem; 3: Moderate problem; 4: Severe problem; 5: Problem as bad as it can be. Sum of all 22 questions constitutes the total SNOT-22 score with a maximum total score equal to 110.
Time frame: Baseline, Day 14 and Day 30
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Cohort - Treatment Arm | PK Cohort: Total Sino-Nasal Outcomes Test Score (SNOT-22) | Baseline | 45.0 units on a scale | Standard Deviation 10.02 |
| Randomized Cohort - Treatment Arm | PK Cohort: Total Sino-Nasal Outcomes Test Score (SNOT-22) | Day 14 | 21.2 units on a scale | Standard Deviation 13.9 |
| Randomized Cohort - Treatment Arm | PK Cohort: Total Sino-Nasal Outcomes Test Score (SNOT-22) | Day 30 | 27.6 units on a scale | Standard Deviation 9.13 |
Secondary
Randomized Cohort: Estimated Frontal Sinus Ostia (FSO) Diameter
The smallest and largest diameters of the FSO determined by an independent, blinded sinus surgeon based on the centralized video-endoscopy review. FSO diameter estimated endoscopically by probing with a 3-mm olive-shaped frontal sinus suction tip and reported in mm.
Time frame: 30 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Cohort - Treatment Arm | Randomized Cohort: Estimated Frontal Sinus Ostia (FSO) Diameter | Largest Diameter | 2.8 mm | Standard Deviation 1.86 |
| Randomized Cohort - Treatment Arm | Randomized Cohort: Estimated Frontal Sinus Ostia (FSO) Diameter | Smallest Diameter | 2.2 mm | Standard Deviation 1.44 |
| Randomized Cohort - Control Arm | Randomized Cohort: Estimated Frontal Sinus Ostia (FSO) Diameter | Largest Diameter | 2.6 mm | Standard Deviation 1.61 |
| Randomized Cohort - Control Arm | Randomized Cohort: Estimated Frontal Sinus Ostia (FSO) Diameter | Smallest Diameter | 2.1 mm | Standard Deviation 1.31 |