Chronic Sinusitis, Nasal Polyposis
Conditions
Keywords
MEDIHONEY, Chronic Rhinosinusitis With Nasal Polyposis, Functional Endoscopic Sinus Surgery
Brief summary
This study will assess the effectiveness of MEDIHONEY® sinus rinses (alone or in combination with intranasal corticosteroids) vs. intranasal corticosteroid sinus rinses on mucosal healing and polyp recurrence in the post-operative period following functional endoscopic sinus surgery.
Detailed description
In patients with refractory CRSwNP, functional endoscopic sinus surgery (FESS), is intended to restore physiologic sinus ventilation and drainage, which can facilitate the gradual resolution of mucosal disease. However, because FESS does not directly treat the underlying inflammatory disorder, a successful sinus surgery must be followed by medical maintenance therapy to control inflammatory processes. The current mainstay of treatment of CRSwNP includes antibiotics and topical and systemic steroids. There is evidence that administration of systemic steroids in the postoperative period for patients who have polyps may have a significant impact on their postoperative course. However, the chance of significant side effects increases with the dose and duration of treatment and therefore the minimum dose necessary to control the disease should be given. Antibiotics also have their limited but documented side effects and can induce resistance. A semi-natural product like manuka honey (brand name MEDIHONEY®), with antibacterial and anti-inflammatory properties, might prove as a useful alternative since it has no major adverse events documented in the literature, does not induce resistance and is effective against resistant pathogens common in this patient population. This study is a prospective, randomized, pilot clinical trial that will determine if the use of MEDIHONEY® sinus rinses (alone or in combination with intranasal steroids) in the postoperative period enhances recovery and prevents polyp recurrence in patients after functional endoscopic sinus surgery (FESS), compared with the standard regimen of topical corticosteroid sinus rinses. The study will collect and compare subjective and objective efficacy assessments of both types of rinses.
Interventions
DEVICEMEDIHONEY®
MEDIHONEY® is a seminatural product with antibacterial and anti-inflammatory properties
DRUGBudesonide
Topical steroid
DRUGNormal saline sinus rinse
8 oz or 4 oz of normal saline with NeilMed sinus rinse bottle
DRUGPrednisone
Post-operatively, 40 mg daily for 7 days
PROCEDUREEndoscopic sinus surgery
Endoscopic sinus surgery to debride polyps and establish adequate sinus drainage
saline nasal mist every hour while awake
Sponsors
University of Vermont Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1\. Age 18 years or older; 2\. Diagnosis of CRSwNP based on the following criteria: * Pattern of symptoms: i. Symptoms present for ≥12 wk * Symptoms for diagnosis: Requires ≥2 of the following symptoms: i. Anterior and/or posterior mucopurulent drainage; ii. Nasal obstruction; iii. Facial pain/pressure/fullness; * Objective documentation: Requires both: 1. Endoscopy to verify the presence of polyps in middle meatus and document presence of inflammation, such as discolored mucus or edema of middle meatus or ethmoid area; and 2. Evidence of rhinosinusitis on imaging by CT (1 obvious polypoid tissue or sinus opacification and/or at least 2mm of mucosal thickening). * Failed medical management (i.e. refractory CRSwNP) and eligible for FESS.
Exclusion criteria
1. Contraindications to oral prednisone or known hypersensitivity to any study medications; 2. Churg Strauss disorder; 3. abnormalities of mucociliary clearance (cystic fibrosis, primary ciliary dyskinesia and Young's syndrome); 4. Diagnosed immunodeficiency; 5. Aspirin-induced asthma (ASA) (aka Samter triad) (a triad of asthma, aspirin and NSAID sensitivity, and nasal/ethmoidal polyposis).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Lund-Kennedy Endoscopic Scores | 119 days | Characteristics of each sinonasal cavity are assessed endoscopically to provide a score based on polyp disease, mucosal edema/crusting/scarring and nasal secretions. A score is provided for the left and right. The scores are totaled to provide a number between 0 and 20. Polyps: 0 = absence of polyp; 1 = polyps in middle meatus only; 2 = polyps beyond middle meatus Edema: 0 = absent; 1 = mild; 2 = severe Discharge: 0 = no discharge; 1 = clear, thin discharge; 2 = thick, purulent discharge Scarring: 0 = absent; 1 = mild; 2 = severe Crusting: 0 = absent; 1 = mild; 2 = severe This scoring system has since been the instrument of choice to endoscopically evaluate outcomes of interventions in non-neoplastic sinonasal disease prospectively over time in research and clinical practice. The higher the score, the worse the outcome. Endoscopy scores from the 3 study groups are compared for the average unit change between baseline and day 119. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nasal Drainage Cultures | 35 days | Nasal drainage cultures from the 3 study groups will be compared for the average percent change between a patient's positive intraoperative cultures compared to the patient's cultures at day 35. |
| Change in Sinonasal Outcome Test (SNOT-22) Questionnaire Score | 119 days | The SNOT-22 consists of 22 questions; items 1 to 12 represent the physical problems associated with rhinosinusitis, items 13 to 18 represent the functional limitations, and items 20 to 22 represent the emotional consequences. Each question is scored by the patient from 0 (no problem) to 5 (the problem is as bad as it can be). The overall score can theoretically range from 0 to 110, with higher scores reflecting more severe quality of life impairment as subjectively reported by the patient. Overall SNOT-22 scores from the 3 study groups are compared for the average change in score from baseline to day 119. |
| Change in SNOT-22 Nasal Symptom Scores | 119 days | The SNOT-22 consists of 22 questions; items 1 to 12 represent the physical problems associated with rhinosinusitis, items 13 to 18 represent the functional limitations, and items 20 to 22 represent the emotional consequences. Each question is scored by the patient from 0 (no problem) to 5 (the problem is as bad as it can be). The first seven questions relate to nasal symptoms. The nasal symptoms score is calculated by summing the scores for these first seven questions. The range is 0 to 35. Higher scores reflect more severe quality of life impairment as subjectively reported by the patient. The nasal symptom scores from the 3 study groups are compared for the average change in score from baseline to day 119. |
Countries
United States
Participant flow
Pre-assignment details
All subjects were enrolled prior to surgery (day 0). Days 0-7 all subjects were treated with oral prednisone once daily, nasal saline irrigation four times daily, and nasal saline misting hourly while awake. Assignment to each arm occurred on day 7. Three enrolled subjects withdrew prior to assignment because they elected to not undergo surgery.
Participants by arm
| Arm | Count |
|---|---|
| Budesonide Rinse Group 1a. Days 0-7: 40 mg prednisone daily, saline sinus rinse 4 times daily, nasal saline spray hourly while awake b. Days 7-91: 8oz saline/budesonide sinus rinse BID c. After day 91: i. In case endoscopy shows any polyps, edema or discharge: Decrease volume to 4 oz budesonide/saline rinse BID. Continue until day 182 ii. In case endoscopy shows no polyps, edema and discharge: Decrease volume to 4 oz budesonide/saline rinse once daily.
Reevaluate at day 119:
1. In case endoscopy shows any polyps, edema or discharge: Return to the initial regimen as per 1.c.i till day 182.
2. In case endoscopy shows no polyps, edema and discharge: Continue as per 1.c.ii till day 182.
Budesonide: Topical steroid Normal saline sinus rinse: 8 oz or 4 oz normal saline with NeilMed sinus rinse bottle Prednisone: Post-operatively 40 mg daily for 7 days Endoscopic sinus surgery: Surgery to debride polyps and establish adequate sinus drainage Nasal saline spray: saline nasal mist every hour while awake | 13 |
| MEDIHONEY® Rinse Alone Group 1. Days 0-7: Same as 1a
2. Days 7-91: 8oz saline sinus rinse followed with 0.5oz of MEDIHONEY® in 50 cc of normal saline
3. After day 91:
i. In case endoscopy shows any polyps, edema or discharge: Decrease volume to 4 oz saline rinse followed with the 50cc of MEDIHONEY® rinse BID. Continue until day 182 ii. In case endoscopy shows no polyps, edema and discharge: Decrease volume to 4 oz saline rinse followed with the 50cc of MEDIHONEY® rinse once daily.
Reevaluate at day 119:
1. In case endoscopy shows any polyps, edema or discharge: Return to the initial regimen as per 1.c.i until day 182
2. In case endoscopy shows no polyps, edema and discharge: Continue as per 1.c.ii till day 182
MEDIHONEY®: A seminatural product with antibacterial and anti-inflammatory properties | 12 |
| MEDIHONEY® and Budesonide Rinse Group 1. Days 0-7: Same as 1a
2. Days 7-91: 8oz saline/budesonide sinus rinse followed by 0.5oz of MEDIHONEY® in 50 cc of normal saline BID
3. After day 91:
i. In case endoscopy shows any polyps, edema or discharge: Decrease volume to 4 oz budesonide/saline rinse followed with 50cc of the MEDIHONEY® rinse BID. Continue with this regimen till day 182.
ii. In case endoscopy shows no polyps, edema and discharge: Decrease volume to 4 oz budesonide/saline rinse followed with 50cc of the MEDIHONEY® rinse once a day.
Reevaluate at day 119:
1. In case endoscopy shows any polyps, edema or discharge: Return to the initial regimen as per 3.c.i till day 182.
2. In case endoscopy shows no polyps, edema and discharge: Continue as per 3.c.ii till day 182. | 12 |
| Total | 37 |
Baseline characteristics
| Characteristic | MEDIHONEY® Rinse Alone Group | Total | Budesonide Rinse Group | MEDIHONEY® and Budesonide Rinse Group |
|---|---|---|---|---|
| Age, Continuous | 51 years STANDARD_DEVIATION 14 | 56 years STANDARD_DEVIATION 14 | 53 years STANDARD_DEVIATION 19 | 58 years STANDARD_DEVIATION 8 |
| Baseline Surgery Score | 13.0 units on a scale STANDARD_DEVIATION 1 | 13.1 units on a scale STANDARD_DEVIATION 1 | 12.8 units on a scale STANDARD_DEVIATION 1 | 13.5 units on a scale STANDARD_DEVIATION 0.9 |
| Current Smoker | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Former Smoker | 4 Participants | 13 Participants | 5 Participants | 4 Participants |
| History of Asthma | 6 Participants | 19 Participants | 7 Participants | 6 Participants |
| History of Bronchiectasis | 1 Participants | 4 Participants | 1 Participants | 2 Participants |
| History of Diabetes | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| History of Environmental Allergies | 7 Participants | 22 Participants | 8 Participants | 7 Participants |
| Lund-Mackay Radiographic Score | 14.8 units on a scale STANDARD_DEVIATION 5.6 | 15.6 units on a scale STANDARD_DEVIATION 6.7 | 15.8 units on a scale STANDARD_DEVIATION 6.6 | 18.3 units on a scale STANDARD_DEVIATION 5.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 37 Participants | 13 Participants | 12 Participants |
| Region of Enrollment United States | 12 participants | 37 participants | 13 participants | 12 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 8 Participants | 30 Participants | 11 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 1 / 12 | 0 / 12 |
| other Total, other adverse events | 1 / 13 | 2 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Change in Lund-Kennedy Endoscopic Scores
Characteristics of each sinonasal cavity are assessed endoscopically to provide a score based on polyp disease, mucosal edema/crusting/scarring and nasal secretions. A score is provided for the left and right. The scores are totaled to provide a number between 0 and 20. Polyps: 0 = absence of polyp; 1 = polyps in middle meatus only; 2 = polyps beyond middle meatus Edema: 0 = absent; 1 = mild; 2 = severe Discharge: 0 = no discharge; 1 = clear, thin discharge; 2 = thick, purulent discharge Scarring: 0 = absent; 1 = mild; 2 = severe Crusting: 0 = absent; 1 = mild; 2 = severe This scoring system has since been the instrument of choice to endoscopically evaluate outcomes of interventions in non-neoplastic sinonasal disease prospectively over time in research and clinical practice. The higher the score, the worse the outcome. Endoscopy scores from the 3 study groups are compared for the average unit change between baseline and day 119.
Time frame: 119 days
Population: The population analyzed for this outcome is the population of participants for which we had data points at day 119. Please note that this is different than the number of participants that completed the study (Budesonide: 13 enrolled, 11 analyzed; MEDIHONEY: 12 enrolled, 6 analyzed; MEDIHONEY and budesonide: 12 enrolled, 9 analyzed).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide Rinse Group | Change in Lund-Kennedy Endoscopic Scores | -8.0 score on a scale | Standard Deviation 3.1 |
| MEDIHONEY® Rinse Alone Group | Change in Lund-Kennedy Endoscopic Scores | -1.5 score on a scale | Standard Deviation 4.6 |
| MEDIHONEY® and Budesonide Rinse Group | Change in Lund-Kennedy Endoscopic Scores | -6.9 score on a scale | Standard Deviation 3.9 |
Secondary
Change in Sinonasal Outcome Test (SNOT-22) Questionnaire Score
The SNOT-22 consists of 22 questions; items 1 to 12 represent the physical problems associated with rhinosinusitis, items 13 to 18 represent the functional limitations, and items 20 to 22 represent the emotional consequences. Each question is scored by the patient from 0 (no problem) to 5 (the problem is as bad as it can be). The overall score can theoretically range from 0 to 110, with higher scores reflecting more severe quality of life impairment as subjectively reported by the patient. Overall SNOT-22 scores from the 3 study groups are compared for the average change in score from baseline to day 119.
Time frame: 119 days
Population: The population analyzed for this outcome is the population of participants for which we had data points at day 119. Please note that this is different than the number of participants that completed the study (Budesonide: 13 enrolled, 11 analyzed; MEDIHONEY: 12 enrolled, 6 analyzed; MEDIHONEY and budesonide: 12 enrolled, 9 analyzed).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide Rinse Group | Change in Sinonasal Outcome Test (SNOT-22) Questionnaire Score | -22.8 score on a scale | Standard Deviation 20.2 |
| MEDIHONEY® Rinse Alone Group | Change in Sinonasal Outcome Test (SNOT-22) Questionnaire Score | -15.3 score on a scale | Standard Deviation 27.4 |
| MEDIHONEY® and Budesonide Rinse Group | Change in Sinonasal Outcome Test (SNOT-22) Questionnaire Score | -25.6 score on a scale | Standard Deviation 16.9 |
Secondary
Change in SNOT-22 Nasal Symptom Scores
The SNOT-22 consists of 22 questions; items 1 to 12 represent the physical problems associated with rhinosinusitis, items 13 to 18 represent the functional limitations, and items 20 to 22 represent the emotional consequences. Each question is scored by the patient from 0 (no problem) to 5 (the problem is as bad as it can be). The first seven questions relate to nasal symptoms. The nasal symptoms score is calculated by summing the scores for these first seven questions. The range is 0 to 35. Higher scores reflect more severe quality of life impairment as subjectively reported by the patient. The nasal symptom scores from the 3 study groups are compared for the average change in score from baseline to day 119.
Time frame: 119 days
Population: The population analyzed for this outcome is the population of participants for which we had data points at day 119. Please note that this is different than the number of participants that completed the study (Budesonide: 13 enrolled, 11 analyzed; MEDIHONEY: 12 enrolled, 6 analyzed; MEDIHONEY and budesonide: 12 enrolled, 9 analyzed).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Budesonide Rinse Group | Change in SNOT-22 Nasal Symptom Scores | -10.0 score on a scale | Standard Deviation 7 |
| MEDIHONEY® Rinse Alone Group | Change in SNOT-22 Nasal Symptom Scores | -5.3 score on a scale | Standard Deviation 15.5 |
| MEDIHONEY® and Budesonide Rinse Group | Change in SNOT-22 Nasal Symptom Scores | -11.7 score on a scale | Standard Deviation 7.9 |
Secondary
Nasal Drainage Cultures
Nasal drainage cultures from the 3 study groups will be compared for the average percent change between a patient's positive intraoperative cultures compared to the patient's cultures at day 35.
Time frame: 35 days
Population: This secondary objective describes analyzing quantitative changes in microbiology between day of surgery and post-operative day 35. These data were not collected, but rather the qualitative data (which microorganisms were present) were. Therefore we are not able to complete analysis on this secondary objective.