The Long-Term Safety of Budesonide for Patients With Chronic Rhinosinusitis

Sinusitis Clinical Trial

Official title:

The Long-Term Safety of Budesonide Via Mucosal Atomization Device and Impregnated Nasal Saline Irrigations for Patients With Chronic Rhinosinusitis - A Prospective Double Cohort Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03584178
• Other study ID #: H18-00458
• Status: Recruiting
• Phase: N/A
• Start date: September 5, 2018
• Est. completion date: December 25, 2021

Study information

• Verified date: September 2019
• Source: St. Paul's Hospital, Canada
• Contact: Amin Javer, MD
• Phone: 6048069926
• Email: sinusdoc[@]me.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Chronic Rhinosinusitis (CRS) is a common disorder of the nose. The current practice at St Paul's Sinus Centre is to prescribe budesonide via the mucosal atomization device or impregnated saline irrigation. Both have shown to be a safe method of administration. A previous study demonstrated a 6% elevation in intraocular pressure and 3% prevalence of asymptomatic AdrenoCorticoTropic Hormone-Axis (ACTH) suppression. However, a baseline measurement was not conducted to ascertain the correlation of these findings with the medication. Therefore, the investigators aim to conduct baseline measurements of IntraOcular Pressure (IOP), ACTH-axis function, and Dual Energy X-ray Absorptiometry (DEXA) scan and obtaining regular measurements of these variables within a 12-month period to further ascertain these previous findings.

Description:

Purpose:

The purpose of this study is to assess the long-term effects of budesonide via MAD (Mucosal Atomization Device) or INSI (Intranasal Saline Irrigation) on intraocular pressure, ACTH-axis function, and bone-density.

Hypothesis:

Budesonide delivered via MAD or INSI will be safe in the long-term (> 12 months) demonstrated objectively via IOP, ACTH stimulation test, and DEXA scan.

Justification:

The safety profile of both MAD and INSI has been widely studied in the literature. Although both modalities are generally considered safe, several studies have demonstrated asymptomatic hypothalamic-pituitary-adrenal axis (HPAA) suppression when used in the long-term. A cross-sectional study at St Paul's Sinus Centre, found 3% of study participants on long-term maintenance treatment via MAD to have asymptomatic HPAA suppression. However, the cross-sectional study design limited the ability to ascertain the timeline for this adverse event.

Although the recent cross-sectional study at St Paul Sinus Centre was the first to study the long-term effects of budesonide via the MAD in CRS patients, it did not include baseline levels of HPAA function and IOP levels which served as a limitation to ascertaining the timeline of the aforementioned adverse events. Additionally, there is currently limited data on the effects of INCS on bone function in the setting of CRS treatment. Therefore, this study aims to prospectively assess the long-term effect of high-dose nasal corticosteroids (i.e. INSI and MAD) in CRS patients. The study design will obtain baseline measurements of ACTH function, IOP measurement, and a DEXA scan to identify and describe the timeline of adverse events should they develop during the 12-month study period. By determining the impact of nasal corticosteroids on these outcomes, potential improvements can be made in the safety monitoring practices of otolaryngologists. This may include more frequent monitoring of intraocular pressure, Bone Mineral Density (BMD), and HPAA-axis function in at-risk populations, development of budesonide tapering guidelines, and improved screening of patient-reported adverse events. Overall, the investigators hope the results from this study will be a step forward in the development of screening guidelines for monitoring patients on long-term IntraNasal CorticoSteroids (INCS) therapy.

Primary Objective:

To assess long-term safety (> 12 months) of budesonide delivered via MAD or INSI as measured objectively via IOP, ACTH stimulation test, and DEXA scan.

Research Design:

A Prospective Double-Cohort Study

Statistical Analysis:

Descriptive statistics will be used to analyze the baseline characteristic data and the data from the administered surveys and objective findings of ACTH stimulation test, IOP measurement, and DEXA scans. In addition, rigorous statistical analysis will be conducted on the Likert scale-based SinoNasal Outcome Test (SNOT-22) and EuroQuol health-related quality of life surveys (EQ-5D-5L). These analyses will include cross-tabulations (Pearson's chi square test) and confidence interval calculations. Due to the variations in baseline intraocular pressure measurements, the investigators will calculate an adjusted difference instead of absolute values.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 25, 2021
• Est. primary completion date: December 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Patients aged between 19 years and above

2. Patients with chronic or recurrent sinusitis (as defined by the American Academy of Otolaryngology) with nasal polyposis

3. Patients with an upcoming Functional Endoscopic Sinus Surgery (FESS) procedure

4. Patients being prescribed INCS for the first time following FESS

Exclusion Criteria:

1. Individuals unable to understand the purpose, methods and conduct of this study

2. Patients unwilling to provide informed consent

3. Patients with significant comorbidities (such as tumour, CF, wegeners granulomatosis, immunocompromised)

4. Patients with a history of pituitary disease

5. Patients with a known hypersensitivity to cortisol, corticotropin, or cosyntropin

6. Patients with history of glaucoma or cataracts

7. Recent use of systemic corticosteroids such as prednisone (within last 3 months)

8. Patients that are not adherent to budesonide via MAD/INSI treatment

Related Conditions & MeSH terms

• Sinusitis

Intervention

Device:
• Budesonide via MAD device
Delivery through Mucosal Atomization Device
• Budesonide via intranasals Saline Irrigation
delivery via nasal irrigation bottle

Locations

Country	Name	City	State
Canada	St Paul Hospital	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
St. Paul's Hospital, Canada

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sinonasal-Outcomes Test-22 (SNOT-22) Questionnaire	This sinus-specific questionnaire is divided into three parts consisting of 22 questions that are related to sinus health and health-related quality of life. This questionnaire was developed to assess symptoms and quality of life in patients suffering from CRS with or without nasal polyposis. Each question is scored on an ordinal, categorical scale ranging from 0 to 5. Patients are instructed to indicate if symptoms are "absent (0)", "very mild (1)", "mild (2)", "moderate (3)", "severe (4)" or "as bad as it can be (5)". The highest score achievable on this questionnaire is 110 points. Higher scores indicate greater symptom severity and burden on daily life. In a validation survey of 2803 subjects, the SNOT-22 showed high internal consistency, test-retest reliability and validity. The SNOT-22 was found to sufficiently distinguish between patients with CRS and healthy controls (P<0.0001, t=85.3).	1 year