Trial of Directed High-dose Nasal Steroids on Residual Smell Loss in Sinus Patients After Sinus Surgery

OVERVIEW:

This is a prospective randomized cohort study assessing the use of directed high-dose nasal
steroids for improving olfactory function after endoscopic sinus surgery for chronic
rhinosinusitis. Up to 70 subjects will be prospectively enrolled from patients visiting the
Department of Otolaryngology-Head and Neck Surgery clinics at the University of North
Carolina (UNC) Hospitals.

VISIT 1/PRE-OPERATIVE VISIT

Visit 1 will be the day of enrollment or the pre-operative visit. During this encounter,
subjects will complete the Rhinosinusitis Disability Index (RSDI), Rhinosinusitis Outcome
Measure 31 (RSOM-31), Sinonasal Outcome Test 22 (SNOT-22), University of Pennsylvania Smell
Identification Test (UPSIT), Phenyl-ethyl-alcohol (PEA) tests and will also have their
Lund-Kennedy scores recorded. Additionally, all subjects will undergo a pre-operative
(standard of care) head CT which will be scored with the Lund-Mackay system. This standard
of care head CT will be billed to the subject's insurance.

VISIT 2/POST-OPERATIVE VISIT(POV) 1

Visit 2 will occur at "post-operative visit 1" or 4-6 weeks after surgery. During this
encounter, subjects will complete the RSDI, RSOM-31, SNOT-22, UPSIT, PEA tests and will also
have their Lund-Kennedy scores recorded. Additionally, all subjects will undergo
post-operative (standard of care) head CT. This standard of care head CT will be billed to
the subject's insurance. Subjects who do have quantitative improvement in olfaction (as
determined by UPSIT category score) will be considered part of the "improved" group and will
simply be followed without an intervention. Subjects who do not have quantitative
improvement in olfaction will be randomized (with a random number generator) into a
"treatment" or an "observation" group. Subjects within the treatment group will be given a
12-week course of directed high-dose nasal steroid irrigation. Pharmacies will bill the
subjects' insurance for the medication. Subjects will be instructed to perform irrigation
twice daily using ½ budesonide respule, 0.5 mg/2mL, applied directly to the nasal mucosa as
described previously. Subjects will be given written instructions on how to perform nasal
irrigation with this medication. Subjects randomized to receive medication will be given
medication diaries and asked to document medication compliance and side effects.

PHONE INTERVIEW (1-2 WEEKS AFTER TREATMENT)

Subjects randomized to the treatment arm will be called 1-2 weeks after initiation of
budesonide treatment to assess medication compliance and side effects. Subjects will be
asked to review their medication diaries when answering questions about compliance and side
effects. As detailed in the data safety monitoring plan, the PI will be alerted if any
subjects are experiencing moderate-severe adverse events or any unexpected side effects.

VISIT 3/"SURVEILLANCE" VISIT

Visit 3 will be a surveillance visit somewhere between post-operative visit 1 (at 4-6 weeks)
and post-operative visit 2 (at 3-4 months). Only patients in the treatment arm will have
this visit. During this visit, subjects will be asked about medication compliance and asked
to demonstrate irrigation technique with nasal saline. Medication diaries will be reviewed
and assessed for compliance and concerning side effects. These diaries will be collected for
future review by the independent data safety reviewer.

VISIT 4/ POST-OPERATIVE VISIT (POV) 2

Visit 4 will occur at post-operative visit 2 or 3-4 months after surgery. During this
encounter, subjects will complete the RSDI, RSOM-31, SNOT-22, UPSIT, PEA tests and will also
have their Lund-Kennedy scores recorded. Subjects in the "non-improved" arm (regardless of
whether they were randomized to receive nasal steroids) will have an additional (for
research purposes only) head CT. This research only head CT will be provided free of charge
by the Department of Otolaryngology's CT scanner.

Medication diaries will be reviewed and assessed for compliance and concerning side effects.
These diaries will be collected for future review by the independent data safety reviewer.

Inclusion Criteria:

- Patients who are otherwise healthy undergoing surgery for treatment of chronic
rhinosinusitis will be evaluated for olfactory dysfunction, and if present, will be
recruited for study participation. The subjects will be included without regard to
their gender, race or ethnicity. Subjects will be identified from patients in the
clinical practices of the Department of Otolaryngology - Head and Neck Surgery at the
University of North Carolina. Only adult patients greater than 18 years old and less
than 85 will be approached for this study, as patient treatment algorithms outside
this range tend to vary with greater frequency. Due to limited resources, only
patients fluent in English will be included, thus minimizing confounding variables
and hurdles to patient communication, as some clinics do not have interpreting
services. Also, most of the quality of life surveys and olfactory testing do not have
non English versions. Only patients with health insurance will be included in the
study in order to ensure all participants have access to the study drug.

Exclusion Criteria:

- If the patient is a premenopausal woman, she will be asked if she is pregnant or
breastfeeding. If she is either of these, she will be excluded from the study. All
remaining women will receive a urine pregnancy test. If this urine pregnancy test is
positive, the patient will be excluded from the study. Thus, for premenopausal female
patients, a negative urine pregnancy test is necessary for inclusion in the study
because of the need for repeat CTs and the possible systemic manifestations due to
steroid irrigation. Further exclusion criteria will include the following:
hypersensitivity to cortisol, history of pituitary disease, and allergic disease with
subsequent anaphylaxis or breathing difficulties. Additionally, patients with a
history of immunodeficiency, autoimmune disease, cystic fibrosis, or previous sinus
surgery will be excluded as these co-morbidities might cloud the relationship between
the treatment and the outcome.