Cystic Fibrosis, Sinusitis
Conditions
Keywords
Cystic fibrosis, chronic sinusitis, mucolytic
Brief summary
Chronic sinusitis is a frequent complication in cystic fibrosis. The aim of this study is to determine whether Pulmozyme(dornase alfa) would maintain sinus health (compared to placebo) in patients with cystic fibrosis who have recently undergone sinus surgery.
Detailed description
AIM: To evaluate the effectiveness of Pulmozyme(dornase alfa) in decreasing post-operative sinusitis symptoms in patients with cystic fibrosis (CF) PROCEDURES: 20 patients with CF will be randomized to receive either Pulmozyme or placebo via nasal inhalation daily for 12 months. Consent will be obtained following surgery and treatment will begin 1 week post-operatively. Monitoring will include examination and recording of adverse effects and follow up weekly for one month and then at 2.5, 6, 9 and 12 months. Outcome measures will include ciliary function testing, pulmonary function testing, sinus questionnaires and CT scan.
Interventions
DRUGPulmozyme (dornase alfa)
2.5 mg/2.5 mL of Pulmozyme (dornase alfa) delivered via Sinustar nasal nebulizer device
DRUGPlacebo
2.5 mL of placebo delivered via Sinustar nebulizer device
Sponsors
Genentech, Inc.
University of Vermont
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical and laboratory diagnosis of cystic fibrosis * Age greater than or equal to 5 years * Forced expiratory volume in 1 second (FEV1) greater than or equal to 40% predicted * Sinus surgery within one week of enrollment
Exclusion criteria
* Pregnancy * Intolerance of orally inhaled Pulmozyme (dornase alfa)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Computed Tomography Evidence of Less Sinus Disease | baseline and 1 year | compare sinus CT pre-op (baseline) to one year after initiation of study drug Difference in pre and post scores by Lund-McKay scoring system are reported (1 year minus baseline) The Lund-Mackay scoring system was used to evaluate the extent and severity of sinusitis. The scale ranges from 0 (best possible outcome with complete lucency of all sinuses) to 24 (worst possible outcome with complete opacification of all sinuses) |
| Improvement in Appearance of Nasal Passages/Sinuses | baseline and 1 year | periodic endoscopic photos of sinuses by ear-nose-throat (ENT) surgeon. The scale for scoring severity of disease ranges from 0 (best possible outcome) to 2 (worst possible outcome). independent blinded scoring by 2 surgeons difference in scores pre and post are reported (1 year minus baseline) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Chronic Sinusitis Survey Score | baseline and 1 year | pre-surgery and end of trial (12 months) Reduction in scores (baseline minus 1 year) are recorded The chronic sinusitis survey consists of 6 questions, ranges from 0-24, a lower score indicates the best possible outcome. |
| Pulmonary Function | baseline and 1 year | prior to surgery and end of study spirometry as measured by forced expiratory volume in 1 second (FEV1) percent predicted. The change over the course of the study (1 year minus baseline) is reported. A higher value indicates a better outcome. |
Countries
United States
Participant flow
Recruitment details
Patients undergoing sinus surgery meeting inclusion criteria were approached in the outpatient or hospital setting
Pre-assignment details
upon providing informed consent, subjects were randomized and blinded to treatment or placebo groups
Participants by arm
| Arm | Count |
|---|---|
| Pulmozyme (Dornase Alfa) 2.5 mg/2.5 mL of intranasal Pulmozyme | 8 |
| Placebo 2.5 mL of placebo comparator | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Pulmozyme (Dornase Alfa) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 6 Participants | 9 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 2 Participants | 7 Participants |
| Region of Enrollment United States | 8 participants | 8 participants | 16 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 8 | 0 / 8 |
| serious Total, serious adverse events | 1 / 8 | 2 / 8 |
Outcome results
Primary
Computed Tomography Evidence of Less Sinus Disease
compare sinus CT pre-op (baseline) to one year after initiation of study drug Difference in pre and post scores by Lund-McKay scoring system are reported (1 year minus baseline) The Lund-Mackay scoring system was used to evaluate the extent and severity of sinusitis. The scale ranges from 0 (best possible outcome with complete lucency of all sinuses) to 24 (worst possible outcome with complete opacification of all sinuses)
Time frame: baseline and 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pulmozyme | Computed Tomography Evidence of Less Sinus Disease | 5.875 units on a scale |
| Placebo | Computed Tomography Evidence of Less Sinus Disease | 3 units on a scale |
p-value: 0.2t-test, 2 sided
Primary
Improvement in Appearance of Nasal Passages/Sinuses
periodic endoscopic photos of sinuses by ear-nose-throat (ENT) surgeon. The scale for scoring severity of disease ranges from 0 (best possible outcome) to 2 (worst possible outcome). independent blinded scoring by 2 surgeons difference in scores pre and post are reported (1 year minus baseline)
Time frame: baseline and 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pulmozyme | Improvement in Appearance of Nasal Passages/Sinuses | 0.2 units |
| Placebo | Improvement in Appearance of Nasal Passages/Sinuses | -1 units |
p-value: 0.048t-test, 2 sided
Secondary
Chronic Sinusitis Survey Score
pre-surgery and end of trial (12 months) Reduction in scores (baseline minus 1 year) are recorded The chronic sinusitis survey consists of 6 questions, ranges from 0-24, a lower score indicates the best possible outcome.
Time frame: baseline and 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pulmozyme | Chronic Sinusitis Survey Score | 8.5 units on a scale |
| Placebo | Chronic Sinusitis Survey Score | 3 units on a scale |
p-value: 0.003t-test, 2 sided
Secondary
Pulmonary Function
prior to surgery and end of study spirometry as measured by forced expiratory volume in 1 second (FEV1) percent predicted. The change over the course of the study (1 year minus baseline) is reported. A higher value indicates a better outcome.
Time frame: baseline and 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pulmozyme | Pulmonary Function | 0.8 percentage of predicted FEV1 |
| Placebo | Pulmonary Function | 5.4 percentage of predicted FEV1 |
p-value: 0.4t-test, 2 sided