Clinical trial NCT04476628: Efficacy of Budesonide Via Delayed Release vs Immediate Release
Official title: Prospective Double-Cohort Study: Comparing Efficacy of Budesonide Via Delayed Release vs Immediate Release After Administration in the Lying Head Back Position
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Chronic Rhinosinusitis (Diagnosis)
Keywords: Budesonide
MAD
CRS
Head Position
Timing of Release
Lead sponsor: St. Paul's Hospital, Canada
Sponsor class: OTHER
First posted: 2020-07-20
Enrollment: 0
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients will be randomly divided to either start with 5MR or 1MR administration methods. They will undergo a 2 week "washout" period before starting their respective administration method. The first administration methods will be once daily for 8 weeks in duration. This is then followed by an additional "washout" period of 2 weeks. Finally, patients will switch to the other administration method for an additional treatment duration of daily application for 8 weeks. We will assess which administration method is more effective. Patients will be asked to administer budesonide daily with a minimum requirement of at least five days a week to ensure changes seen are related to the appropriate treatment arm. The "washout" period will involve standard of care daily non-medicated intranasal saline irrigation. Data will be collected at baseline, 2 weeks, 10 weeks, 12 weeks, and lastly 20 weeks follow-up visit.
Primary purpose: TREATMENT

Brief summary: The aim of this study is to compare the efficacy of intranasal budesonide administration with lying head back position and a 5 mins time to release of medication (5MR) compared to 1 min time to release (1MR) in chronic rhinosinusitis patients (CRS). Participants will be instructed to administer via mucosal automatization device (MAD) with either of the two treatment approaches daily for 5 to 7 days per week and 8 weeks total. This is a crossover study design so each participants will be placed in the other treatment approach for an additional 8 weeks of treatment. Moreover, there will be a "washout" of 2 weeks after baseline assessment and before the first treatment, as well as a second "washout" of 2 weeks between the two treatment approaches. The participants will also complete study related procedures such as endoscopic evaluation, cultures, and two questionnaires throughout the study period. The investigators hypothesize that Budesonide delivered to the sinuses with a 5 minute time to release of medication will be more effective at decreasing inflammation when compared to a 1 minute time to release of medication after administration.

Detailed description: Objective

To compare the efficacy of 1 minute versus 5 minutes time to release of budesonide with lying head back position following administration via mucosal atomization device (MAD).

Hypothesis

Budesonide delivered to the sinuses with lying head back position and a 5 minute time to release (5MR) of medication will be more effective at decreasing inflammation both objectively and subjectively when compared to 1 minute time to release (1MR) of medication after administration.

Baseline and Follow-up Visits Evaluation:

The following information will be obtained from each participant

Baseline Demographic Data: Age, sex, smoking status, CRS subtype, pre-existing comorbidities, history of asthma, history of previous surgery, history of previous medications including oral and inhaled corticosteroids.

Clinical Data: Modified Lund-Kennedy (MLK) scores, sinonasal cultures, Sino-nasal Outcome Test-22 (SNOT-22), EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) scores, and culture.

Conduct of Study:

The proposed study is a single blind randomized, controlled crossover study at of 20 weeks in duration. Participants who have CRS and who meet the inclusion and exclusion criteria, will be invited to participate in this study.

Participants will undergo a 2 week "washout" period before starting their respective administration method. The first administration methods will be once daily for 8 weeks in duration. This is then followed by an additional "washout" period of 2 weeks. Finally, participants will switch to the other administration method for an additional treatment duration of daily application for 8 weeks. The goal is to assess which administration method is more effective. Participants will be asked to administer budesonide daily with a minimum requirement of at least five days a week to ensure changes seen are related to the appropriate treatment arm. The "washout" period will involve standard of care daily non-medicated intranasal saline irrigation. Data will be collected at baseline, 2 weeks, 10 weeks, 12 weeks, and lastly 20 weeks follow-up visit. SNOT-22 questionnaires, EQ-5D-5L questionnaires, endoscopic evaluation, and Modified Lund Kennedy Scores will each be completed at baseline and then again at 2 weeks, 10 weeks, 12 weeks, and 20 weeks.

Upon enrolment in the study, participants will be randomly divided to either start with 5MR or 1MR administration methods through 1:1 block randomization. In addition, demographic data and clinical data will be obtained by the investigators.

Management of Patient Care:

The clinical care remains the same for participants participating in this study; however, there is a possibility that some participants will experience an increased frequency of visits to the clinic with some being spaced 2 weeks apart. The increased appointments are required to effectively transition each participants into the different treatment types and also to acquire additional outcome measures. This will be clearly explained to each participant to ensure that they are aware of the additional appointments compared to standard of care. Otherwise, there are no additional risks imposed on the study participants. Participants have the right to withdraw from the study at any time. Participants who meet any of the exclusion criteria that were not noted at the beginning of the study will be removed from this study and the physician will discuss the future management options with the participant.

Sample Size:

A recruitment goal of 60 participants (30 participants per study arm) is expected to demonstrate an effect for the study. To account for a drop-out rate of 25% the investigators plan to recruit 40 participants in each arm.

The washout periods included in the crossover study design will allow for more control in regards to reducing confounding variables. In particular, this allows participants to start at a similar baseline by using the same standard of treatment with Budesonide for the 2 weeks of washout before going into the 5MR or 1MR treatments.

Analysis:

Descriptive statistics will be used to analyze the baseline characteristic data and the data from the administered surveys and objective findings of cultures and MLK scores. In addition, rigorous statistical analysis will be conducted on the Likert scale-based SNOT-22 and EQ-5D-5L surveys. These analyses will include paired t tests with repeated measured ANOVA for validation and confidence intervals.

Safety Monitoring:

Participants who experience signs and symptoms of budesonide reaction will be noted and the code will be broken so that a discussion can occur between the research supervisor and the participants regarding the use.

All expected and unexpected adverse events will be recorded and graded by the research supervisor. Stable chronic conditions, which are present prior to the clinical trial entry and do not worsen, are not considered adverse events and will be accounted for in the participant's medical history.

During each participant visit, the research supervisor will ask appropriate questions and perform a physical exam to elicit any adverse events. The research supervisor will also review any relevant clinical data and laboratory investigations with the partcicpant. All reportable adverse events will be recorded on appropriate case report form. The research supervisor will also write the stop date, the severity of the AE and his judgment of the AE's relationship to the study.

A Serious Adverse Event (SAE) is defined as an AE meeting one of the following:

Death occurring between Day 0 and 182 days (6 months) of the study. Life Threatening Event (defined as a participant at immediate risk of death at the time of the event) In-participant hospitalization or prolongation of existing hospitalization between Day 0 and 42 of the study.

Results in a persistent or significant disability/incapacity In the event of SAE, the research supervisor will discuss with the partcipant (or next of kin) whether there is a relationship between the study and the SAE. If there is a relationship, the PI will be responsible for coordinating care for the participant until the SAE has been addressed.

Pregnancy During the Trial Participants will be responsible for determining if they are pregnant or become pregnant during the study. If participants notify the PI they are pregnant, they will be removed from the study and the medical management options will be discussed.

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 or without nasal polyposis or allergic fungal rhinosinusitis.
3. Patients currently on budesonide or being prescribed budesonide for the first time
4. Minimum Modified Lund Kennedy score of 2.

Exclusion Criteria:

1. Individuals unable to understand the purpose, methods and conduct of this study
2. Patients unwilling to provide informed consent
3. Are immuno-compromised, and have impairment in mucociliary function (e.g., cystic fibrosis, Kartagener syndrome)
4. Have autoimmune diseases affecting the upper airway (eg Systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis etc)
5. Have sinonasal tumors
6. Patients with a history of pituitary disease
7. Patients with a known hypersensitivity to cortisol, corticotropin, or cosyntropin
8. Recent use of systemic corticosteroids such as prednisone (within last 3 months)
9. Patients who are pregnant or breastfeeding

Primary outcomes:
measure: Change in Modified Lund Kennedy Score
timeFrame: baseline and 20 weeks
measure: Change in Sinonasal-Outcomes Test-22 (SNOT-22) Score
timeFrame: baseline and 20 weeks
Secondary outcomes:
measure: Change EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Score
timeFrame: baseline and 20 weeks
measure: Change in sinus culture results
timeFrame: baseline and 20 weeks
Other outcomes:
Locations:
Study officials:
affiliation: The University of British Columbia and St. Paul's Sinus Centre
name: Amin JAver, MD
role: PRINCIPAL_INVESTIGATOR
References: