Chronic Rhinosinusitis, Endoscopic Sinus Surgery
Conditions
Brief summary
Endoscopic sinus surgery (ESS) is widely considered to be the gold standard in the surgical management of chronic rhinosinusitis (CRS) that has failed maximal medical therapy. Nevertheless, the postoperation medical therapy was considered as a crucial procedure for the success of ESS. Both glucocorticoids and macrolide antibiotics have been recommended for the treatment of CRS, but their effect as postoperation medical therapies of ESS need more clinical data to clarify. The purpose of this prospective, randomized,study is to determine the effect of glucocorticoids and macrolide antibiotics for the postoperation medical therapy of ESS in different subtypes of CRS.
Detailed description
Chronic rhinosinusitis (CRS) is a multifactorial inflammatory disorder that causes various symptoms including nasal obstruction, rhinorrhea, olfactory dysfunction, facial pain, and headache . Endoscopic sinus surgery (ESS) is usually recommended for patients who do not response well to conservative treatments. Although surgery is effective to alleviate symptoms and improve the quality of life of CRS patients, a followed long-term postoperative medical treatment is indispensable. Current European and American guidelines recommend glucocorticoids and antibiotics as the primary pharmacotherapeutic approaches for CRS before and after ESS. However, there are a number of CRS patients not responding well to glucocorticoid treatment and conflicting results exist regarding the efficacy of long-term, low-dose macrolide treatment. One potential reason is that CRS is a heterogeneous group of disorders unified by similar clinical presentations and its phenotypes and/or endotypes may be important factors determining the efficacy of treatments.
Interventions
DRUGClarithromycin
Clarithromycin 250 mg tablet once daily for 3 months
DRUGGlucocorticoid
Fluticasone propionate nasal spray 200 μg/d for 3 months
Sponsors
National Natural Science Foundation of China
Zheng Liu
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Meeting the CRS diagnostic criteria including CRSsNP and CRSwNP based on the EP3OS definition * Age ≥16 and ≤70 years * Chinese of either sex * Failure to conventional medical therapies according to EP3OS recommendation
Exclusion criteria
* Pregnant or breast-feeding women * Cystic fibrosis * Congenital ciliary dyskinesia * Sinonasal fungal disease * Systemic vasculitis * Granulomatous disease * Tumor * Immunodeficiency * Allergic to clarithromycin or topical corticosteroid * With an upper respiratory tract infection within 4 weeks of entering the study * With serious metabolic, cardiovascular, autoimmune, neurology, blood, digestive, cerebrovascular, respiratory system disease, or any disease interfering with the evaluation of results or affecting subjects' safety such as glaucoma and tuberculosis * With emotional or mental problems * Have received immunotherapy within the previous 3 months * Have had a history of local or systemic medications, such as glucocorticoids and macrolides within 4 weeks * Have had an acute asthmatic within the 4 weeks before entering the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Subjective Symptoms Visual Analog Scores (VAS) | Scores will be recorded just before ESS and at 1-, 3-, 6- and 12-month follow-up visit. | The treatment will begin one week after ESS. Symptoms visual analog scores (VAS) were recorded just before ESS and at 1-, 3-, 6- and 12-month follow-up visit. All of the patients were assessed by using symptom questionnaire after enrollment and at follow-up visits. Subjective symptoms were scored by patients on a VAS of 0-10, with 0 being no complaint whatsoever and 10 being the worst imaginable complaint.Five major symptoms were focused on: nasal obstruction, rhinorrhea, loss of sense of smell, facial pain or pressure, and headache. Total VAS score was calculated based on the sum of VAS scores of these five symptom domains. Total subjective symptoms VAS range: 0\ 50, with higher scores indicating greater severity of symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Nasal Endoscopic Scores | Scores will be recorded just before ESS and at 1-, 3-, 6- and 12-month follow-up visit. | Nasal endoscopic evaluation was performed by the senior investigator who remained blinded to the treatment, including poly size: 0, absence of polyps; 1, polyps in middle meatus only; 2, polyps beyond middle meatus but not blocking the nose completely; and 3, polyps completely obstructing the nose; discharge: 0, no discharge; 1, clear thin discharge; 2, thick purulent discharge; edema: 0, no edema; 1, mild edema; 2, severe edema; crusting: 0, no crusting; 1, mild crusting; 2, severe crusting; scarring: 0, no scarring; 1, mild scarring; 2, severe scarring). Each side was graded separately, and the scores from both sides were added to determine the overall scores for a particular domain. The total endoscopy score was calculated based on the sum of scores of these endoscopic domains. Endoscopic scores were also recorded before ESS (baseline) and at 1-, 3-, 6- and 12-month follow-up visits. Total endoscopy score range: 0\ 22, with higher scores indicating greater severity. |
Other
| Measure | Time frame |
|---|---|
| Measurement of Protein Levels of Inflammatory Molecules in Tissues | Polyp tissues from CRSwNP patients and diseased sinus mucosa from CRSsNP patients will be collected during surgery. |
Countries
China
Participant flow
Pre-assignment details
Patients meeting the Chronic rhinosinusitis (CRS) diagnostic criteria outlined in the European Position Paper on Rhinosinusitis and Nasal polyps (EP3OS) definition were enrolled. Three subtypes CRS included: CRS without nasal polyps (CRSsNP); non-eosinophilic CRS with nasal polyps (Non-Eos CRSwNP); eosinophilic CRS with nasal polyps (Eos CRSwNP).
Participants by arm
| Arm | Count |
|---|---|
| Glucocorticoid Fluticasone propionate nasal spray
Glucocorticoid: Fluticasone propionate nasal spray 200 μg/d for 3 months | 93 |
| Clarithromycin Clarithromycin tablet
Clarithromycin: Clarithromycin 250 mg tablet once daily for 3 months | 94 |
| Total | 187 |
Baseline characteristics
| Characteristic | Clarithromycin | Glucocorticoid | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 7 Participants | 12 Participants |
| Age, Categorical >=65 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 86 Participants | 84 Participants | 170 Participants |
| Age, Continuous | 39.9 years STANDARD_DEVIATION 14.2 | 40.4 years STANDARD_DEVIATION 12.6 | 40.2 years STANDARD_DEVIATION 13.4 |
| Region of Enrollment China | 94 participants | 93 participants | 187 participants |
| Sex: Female, Male Female | 42 Participants | 38 Participants | 80 Participants |
| Sex: Female, Male Male | 52 Participants | 55 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 93 | 5 / 94 |
| serious Total, serious adverse events | 0 / 93 | 0 / 94 |
Outcome results
Primary
Total Subjective Symptoms Visual Analog Scores (VAS)
The treatment will begin one week after ESS. Symptoms visual analog scores (VAS) were recorded just before ESS and at 1-, 3-, 6- and 12-month follow-up visit. All of the patients were assessed by using symptom questionnaire after enrollment and at follow-up visits. Subjective symptoms were scored by patients on a VAS of 0-10, with 0 being no complaint whatsoever and 10 being the worst imaginable complaint.Five major symptoms were focused on: nasal obstruction, rhinorrhea, loss of sense of smell, facial pain or pressure, and headache. Total VAS score was calculated based on the sum of VAS scores of these five symptom domains. Total subjective symptoms VAS range: 0\ 50, with higher scores indicating greater severity of symptoms.
Time frame: Scores will be recorded just before ESS and at 1-, 3-, 6- and 12-month follow-up visit.
Population: A total of 187 patients met the study eligibility criteria. Seven patients in fluticasone propionate group and 8 patients in clarithromycin group dropped out because of nonadherence.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glucocorticoid | Total Subjective Symptoms Visual Analog Scores (VAS) | 6-month | 5.9 score on a scale | Standard Deviation 4.5 |
| Glucocorticoid | Total Subjective Symptoms Visual Analog Scores (VAS) | Baseline | 20.4 score on a scale | Standard Deviation 8.1 |
| Glucocorticoid | Total Subjective Symptoms Visual Analog Scores (VAS) | 1-month | 9.7 score on a scale | Standard Deviation 5.2 |
| Glucocorticoid | Total Subjective Symptoms Visual Analog Scores (VAS) | 12-month | 5.6 score on a scale | Standard Deviation 5.3 |
| Glucocorticoid | Total Subjective Symptoms Visual Analog Scores (VAS) | 3-month | 7.0 score on a scale | Standard Deviation 4.2 |
| Clarithromycin | Total Subjective Symptoms Visual Analog Scores (VAS) | 12-month | 4.8 score on a scale | Standard Deviation 5 |
| Clarithromycin | Total Subjective Symptoms Visual Analog Scores (VAS) | 3-month | 5.8 score on a scale | Standard Deviation 4.3 |
| Clarithromycin | Total Subjective Symptoms Visual Analog Scores (VAS) | 6-month | 4.7 score on a scale | Standard Deviation 4.2 |
| Clarithromycin | Total Subjective Symptoms Visual Analog Scores (VAS) | Baseline | 20.7 score on a scale | Standard Deviation 7.8 |
| Clarithromycin | Total Subjective Symptoms Visual Analog Scores (VAS) | 1-month | 8.9 score on a scale | Standard Deviation 5 |
Secondary
Total Nasal Endoscopic Scores
Nasal endoscopic evaluation was performed by the senior investigator who remained blinded to the treatment, including poly size: 0, absence of polyps; 1, polyps in middle meatus only; 2, polyps beyond middle meatus but not blocking the nose completely; and 3, polyps completely obstructing the nose; discharge: 0, no discharge; 1, clear thin discharge; 2, thick purulent discharge; edema: 0, no edema; 1, mild edema; 2, severe edema; crusting: 0, no crusting; 1, mild crusting; 2, severe crusting; scarring: 0, no scarring; 1, mild scarring; 2, severe scarring). Each side was graded separately, and the scores from both sides were added to determine the overall scores for a particular domain. The total endoscopy score was calculated based on the sum of scores of these endoscopic domains. Endoscopic scores were also recorded before ESS (baseline) and at 1-, 3-, 6- and 12-month follow-up visits. Total endoscopy score range: 0\ 22, with higher scores indicating greater severity.
Time frame: Scores will be recorded just before ESS and at 1-, 3-, 6- and 12-month follow-up visit.
Population: A total of 187 patients met the study eligibility criteria. Seven patients in fluticasone propionate group and 8 patients in clarithromycin group dropped out because of nonadherence.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glucocorticoid | Total Nasal Endoscopic Scores | 3-month | 3.7 score on a scale | Standard Deviation 2.8 |
| Glucocorticoid | Total Nasal Endoscopic Scores | 6-month | 3.1 score on a scale | Standard Deviation 2.6 |
| Glucocorticoid | Total Nasal Endoscopic Scores | 1-month | 5.3 score on a scale | Standard Deviation 2.3 |
| Glucocorticoid | Total Nasal Endoscopic Scores | 12-month | 2.7 score on a scale | Standard Deviation 2.6 |
| Glucocorticoid | Total Nasal Endoscopic Scores | Baseline | 8.2 score on a scale | Standard Deviation 2.9 |
| Clarithromycin | Total Nasal Endoscopic Scores | 12-month | 2.1 score on a scale | Standard Deviation 2.4 |
| Clarithromycin | Total Nasal Endoscopic Scores | Baseline | 7.6 score on a scale | Standard Deviation 2.9 |
| Clarithromycin | Total Nasal Endoscopic Scores | 1-month | 4.7 score on a scale | Standard Deviation 2.2 |
| Clarithromycin | Total Nasal Endoscopic Scores | 6-month | 2.1 score on a scale | Standard Deviation 2.2 |
| Clarithromycin | Total Nasal Endoscopic Scores | 3-month | 3 score on a scale | Standard Deviation 2.4 |
Other Pre-specified
Measurement of Protein Levels of Inflammatory Molecules in Tissues
Time frame: Polyp tissues from CRSwNP patients and diseased sinus mucosa from CRSsNP patients will be collected during surgery.