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

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.

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.

Study Overview

• Status: Unknown
• Conditions: Sinusitis
• Intervention / Treatment: Device: Budesonide via MAD device; Device: Budesonide via intranasals Saline Irrigation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Recruiting
      • St Paul Hospital
      • Contact: Amin Javer, MD; Phone Number: 6048069926; Email: sinusdoc@me.com
      • Contact: Sara Derikvand, PhD; Phone Number: 6048069926; Email: stpaulsinusresearch@gmail.com
      • Principal Investigator: Amin R Javer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mucosal Atomization Device; Budesonide via MAD Device	Device: Budesonide via MAD device; Delivery through Mucosal Atomization Device; Other Names: Budesonide via Mucosal Atomization Device
Experimental: Intranasals Saline Irrigation; Budesonide via Intranasals Saline Irrigation	Device: Budesonide via intranasals Saline Irrigation; delivery via nasal irrigation bottle; Other Names: Intranasals Saline Irrigation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: St. Paul's Hospital, Canada
• Investigators: Principal Investigator: Amin Javer, MD, University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2018
• Primary Completion (Anticipated): December 25, 2020
• Study Completion (Anticipated): December 25, 2021

Study Registration Dates

• First Submitted: June 18, 2018
• First Submitted That Met QC Criteria: July 10, 2018
• First Posted (Actual): July 12, 2018

Study Record Updates

• Last Update Posted (Actual): September 20, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Intraocular pressure; MAD; Bone density; Budesonide; INSI; ACTH-axis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Paranasal Sinus Diseases; Nose Diseases; Sinusitis; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: H18-00458

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No