Clinical trial NCT03584178: The Long-Term Safety of Budesonide for Patients With Chronic Rhinosinusitis
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sinusitis
Keywords: ACTH-axis
Budesonide
MAD
INSI
Intraocular pressure
Bone density
Lead sponsor: St. Paul's Hospital, Canada
Sponsor class: OTHER
First posted: 2018-07-12
Enrollment: 100
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Sinonasal-Outcomes Test-22 (SNOT-22) Questionnaire
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: St Paul Hospital
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Amin Javer, MD
role: PRINCIPAL_INVESTIGATOR
References: