Chronic Rhinosinusitis
Conditions
Brief summary
The purpose of this study is to treat patients with a diagnosis of chronic rhinosinusitis (CRS) and a history of bilateral endoscopic sinus surgery during times of worsening symptoms and signs of acute infection on nasal endoscopy with one of two treatments: (1) oral antibiotics and twice daily intranasal saline irrigations or (2) oral placebo and twice daily intranasal antibiotic irrigations. The two treatments will be compared to see if there is any difference in patient outcomes. This will help guide treatment strategies for patients with CRS in the future.
Detailed description
See brief summary.
Interventions
DRUGnebulized levofloxacin
Sponsors
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults (age ≥ 18). 2. Diagnosis of CRS. 3. Worsening sinonasal symptoms. 4. Previous bilateral endoscopic sinus surgery (ESS) (including maxillary antrostomy and anterior ethmoidectomy). 5. English speaking. 6. Open sinuses (open middle meatus bilaterally; determined on endoscopy). 7. Positive sinonasal culture (1+ or greater) with sensitivity to one of the pre-chosen antibiotic regimens.
Exclusion criteria
1. Patients \< 18 years of age. 2. Treatment with systemic or topical antibiotics within the last 1 month. 3. Pregnant women. 4. Non-English speaking persons. 5. Systemically ill at initial visit necessitating treatment prior to culture data. 6. Allergies to chosen susceptible antibiotics. 7. Sinonasal culture with less than 1+ growth. 8. Multiple organisms grown on culture that are not sensitive to a single antibiotic. 9. Patients with ciliary function disorders (cystic fibrosis, Kartagener's syndrome, ciliary dyskinesia). 10. Patients with immunodeficiencies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Rhinosinusitis Disability Index (RSDI) Score | Baseline and 14 days after treatment | The Rhinosinusitis Disability Index is a 30-item questionnaire completed by the patient or subject. Each item has a value of zero to four, a higher score indicates a self-perception of worse symptoms. The minimum score is zero and the maximum score is 120. The difference score here is the post-treatment score minus the pre-treatment score, with lower meaning more improvement |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sino-nasal Outcome Test (SNOT-22) Score | Baseline and 14 days after treatment | The Sino-nasal outcome test is a 22-item questionnaire completed by the patient or subject. Each item has a value of zero to five, a higher score indicates a self-perception of worse symptoms. The minimum score is zero and the maximum score is 110. The difference score here is the post-treatment score minus the pre-treatment score, with lower meaning more improvement |
| Change in Bilateral Endoscopy Findings Using POSE Score | Baseline and 14 days after treatment | The Perioperative Sinus Endoscopy (POSE) instrument is a specific tool to endoscopically assess the sinus cavities of patients who have undergone endoscopic sinus surgery. Each POSE score has a minimum of 0 and a maximum of 16, with a higher score indicating a worse outcome. Here, the Left and Right POSE scores are summed and the difference between baseline and the 14 day after treatment is reported. The change in bilateral POSE score can in principle be -32 to +32, with increased scores indicating worse outcome and negative scores indicating improvement over the treatment period. |
| Number of Participants With Post-treatment Culture Negativity | 14 days after treatment | Post-treatment culture negativity, defined as less than 1+ growth of organisms. A subject is counted '1' if both nares are free of bacterial growth, and '0' if growth is 1+ of more |
| Mean Change in the Total Bacterial Community | Baseline and 14 days after treatment | The bacterial community was determined using a 16S rRNA quantitative PCR processed using Quantitative Insights into Microbial Ecology (QIIME) software, version 1.8 to yield the number of operational taxonomic units in each subject sample. The count has a minimum of zero with an increasing score indicating a larger number of distinct bacterial species. |
Countries
United States
Participant flow
Pre-assignment details
8 participants screen failed before randomization to the intervention.
Participants by arm
| Arm | Count |
|---|---|
| Oral Placebo With Nebulized Intranasal Levofloxacin Placebo oral tablet by mouth daily for 14 consecutive days along with nebulized levofloxacin 125 mg twice daily for 14 consecutive days
oral levofloxacin
nebulized levofloxacin | 12 |
| Oral Antibiotics With Nebulized Intranasal Placebo Levofloxacin 500 mg by mouth once daily for 14 consecutive days, along with intranasal placebo solution twice daily for 14 consecutive days.
oral levofloxacin
nebulized levofloxacin | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Oral Placebo With Nebulized Intranasal Levofloxacin | Oral Antibiotics With Nebulized Intranasal Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 4 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12 Participants | 13 Participants | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 12 Participants | 13 Participants | 25 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 12 participants | 13 participants | 25 participants |
| Sex: Female, Male Female | 11 Participants | 13 Participants | 24 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 13 |
| other Total, other adverse events | 5 / 12 | 9 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 |
Outcome results
Primary
Change in Rhinosinusitis Disability Index (RSDI) Score
The Rhinosinusitis Disability Index is a 30-item questionnaire completed by the patient or subject. Each item has a value of zero to four, a higher score indicates a self-perception of worse symptoms. The minimum score is zero and the maximum score is 120. The difference score here is the post-treatment score minus the pre-treatment score, with lower meaning more improvement
Time frame: Baseline and 14 days after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Placebo With Nebulized Intranasal Levofloxacin | Change in Rhinosinusitis Disability Index (RSDI) Score | -8.000 units on a scale | Standard Deviation 29.47 |
| Oral Antibiotics With Nebulized Intranasal Placebo | Change in Rhinosinusitis Disability Index (RSDI) Score | -14.82 units on a scale | Standard Deviation 13.49 |
p-value: 0.505ANOVA
Secondary
Change in Bilateral Endoscopy Findings Using POSE Score
The Perioperative Sinus Endoscopy (POSE) instrument is a specific tool to endoscopically assess the sinus cavities of patients who have undergone endoscopic sinus surgery. Each POSE score has a minimum of 0 and a maximum of 16, with a higher score indicating a worse outcome. Here, the Left and Right POSE scores are summed and the difference between baseline and the 14 day after treatment is reported. The change in bilateral POSE score can in principle be -32 to +32, with increased scores indicating worse outcome and negative scores indicating improvement over the treatment period.
Time frame: Baseline and 14 days after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Placebo With Nebulized Intranasal Levofloxacin | Change in Bilateral Endoscopy Findings Using POSE Score | -2.889 units on a scale | Standard Deviation 5.442 |
| Oral Antibiotics With Nebulized Intranasal Placebo | Change in Bilateral Endoscopy Findings Using POSE Score | -4.545 units on a scale | Standard Deviation 2.806 |
p-value: 0.39ANOVA
Secondary
Change in Sino-nasal Outcome Test (SNOT-22) Score
The Sino-nasal outcome test is a 22-item questionnaire completed by the patient or subject. Each item has a value of zero to five, a higher score indicates a self-perception of worse symptoms. The minimum score is zero and the maximum score is 110. The difference score here is the post-treatment score minus the pre-treatment score, with lower meaning more improvement
Time frame: Baseline and 14 days after treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Placebo With Nebulized Intranasal Levofloxacin | Change in Sino-nasal Outcome Test (SNOT-22) Score | -2.333 units on a scale | Standard Deviation 33.02 |
| Oral Antibiotics With Nebulized Intranasal Placebo | Change in Sino-nasal Outcome Test (SNOT-22) Score | -18.73 units on a scale | Standard Deviation 12.37 |
Secondary
Mean Change in the Total Bacterial Community
The bacterial community was determined using a 16S rRNA quantitative PCR processed using Quantitative Insights into Microbial Ecology (QIIME) software, version 1.8 to yield the number of operational taxonomic units in each subject sample. The count has a minimum of zero with an increasing score indicating a larger number of distinct bacterial species.
Time frame: Baseline and 14 days after treatment
Population: Data was only collected on the first consecutive 8 randomized participants and had equal numbers in each group
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Placebo With Nebulized Intranasal Levofloxacin | Mean Change in the Total Bacterial Community | 17.40 operational taxonomic units | Standard Deviation 9.53 |
| Oral Antibiotics With Nebulized Intranasal Placebo | Mean Change in the Total Bacterial Community | 6.700 operational taxonomic units | Standard Deviation 7.404 |
Secondary
Number of Participants With Post-treatment Culture Negativity
Post-treatment culture negativity, defined as less than 1+ growth of organisms. A subject is counted '1' if both nares are free of bacterial growth, and '0' if growth is 1+ of more
Time frame: 14 days after treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Placebo With Nebulized Intranasal Levofloxacin | Number of Participants With Post-treatment Culture Negativity | 5 Participants |
| Oral Antibiotics With Nebulized Intranasal Placebo | Number of Participants With Post-treatment Culture Negativity | 2 Participants |
p-value: 0.036ANOVA