The Impact Of The Addition Of Budesonide To Low-Pressure, High-Volume Saline Sinus Irrigation For Chronic Rhinosinusitis

NCT ID: NCT02696850

Last Updated: 2019-09-03

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-01

Study Completion Date

2017-04-13

Brief Summary

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The goal of this research project is to explore the impact of the addition of budesonide to high-volume, low-pressure nasal sinus saline irrigation (aka "Neti-Pot"-type systems) for patients with chronic rhinosinusitis with or without nasal polyps.

Detailed Description

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Study Design

Double-blind placebo-controlled randomized clinical trial

Subjects Up to 80 adult patients with complaints of purulent (not clear) nasal drainage accompanied by nasal obstruction, facial pain-pressure-fullness, or both and reduction or loss of smell for 12 weeks or greater.

Inclusion Criteria:

Twelve (12) weeks or longer of two or more of the following signs and symptom consistent with chronic rhinosinusitis (CRS):

mucopurulent drainage (anterior, posterior, or both), nasal obstruction (congestion),facial pain-pressure-fullness, and decreased sense of smell

AND inflammation documented by one or more of the following findings:

* purulent (not clear) mucus or edema in the middle meatus or ethmoid region,
* polyps in nasal cavity or the middle meatus, and/or
* radiographic imaging showing inflammation of the paranasal sinuses

Exclusion criteria:

* Unable to speak English
* History of comorbid ciliary dyskinesia, cystic fibrosis or any other mucociliary condition
* Dependence on prolonged corticosteroid therapy for comorbid condition, such as asthma and chronic obstructive pulmonary disease.
* History of oral or systematic antibiotic use in the past 2 weeks
* History of nasal or sinus surgery within past 6 weeks
* History of cerebrospinal fluid leak
* History of allergy to budesonide or other topical steroids
* Pregnant or breast feeding
* Current infection or history of one of the following infections: Tuberculosis (TB) lung infection, or Herpes infection of the eye.
* Baseline SNOT-22 total scores below 9 were excluded due to the inability to achieve a minimally clinically improved difference

Variables of Interest Demographic - age, gender, and race. Index condition - Duration of CRS symptoms, response to previous treatments Co-morbid conditions - Presence and severity of general comorbid conditions will be assessed with ACE-27. Presence of rhinosinusitis-specific comorbidities will include: inhalant allergies, asthma, and aspirin sensitivity Previous sinus and/or nasal surgery - Previous sinus and/or nasal surgery, including functional endoscopic sinus surgery, turbinate reduction, and septoplasty will be captured and duration since surgery to time of enrollment.

Randomization The study statistician, Dr. Dorina Kallogjeri, will use a randomized block design for study drug assignment. To ensure balance in key clinical features thought to be related to outcome, subjects will be stratified into one of four categories based on the two main clinical features: nasal polyps (presence/absence) and history of previous sinus surgery (yes/no) prior to randomization.

Intervention The study intervention will be budesonide powder (0.5 mg/capsule) or an identical-appearing placebo product containing lactose. All subjects will be provided with the 8-ounce (240 ml) NeilMed Sinus Rinse Regular Bottle Kit and a one-month supply of USP Grade Sodium Chloride \& Sodium Bicarbonate Mixture (pH balanced, Isotonic \& Preservative \& Iodine Free) commercially prepared packettes. Subjects may substitute the NeilMed Sinus Rinse Regular Bottle Kit for a nasal irrigation system, which in the opinion of the Principal Investigator, is similar to the NeilMed system and embodies the low-pressure, high-volume concept of nasal irrigation. Subjects will need to purchase distilled water or boil tap water for five minutes for use with the saline irrigation. Subjects will be required to dissolve the contents of two capsules into the 8-ounce (240 ml) NeilMed Sinus Rinse Regular Bottle along with the saline rinse. All subjects will be instructed to irrigate both right and left nasal cavity with one-half of the contents of the nasal rinse once daily. The subjects will receive written instructions and a video prior to initiation of the intervention to ensure proper delivery.

Each study bottle will contain 60 capsules of Budesonide or placebo and will be assigned with a number from 1-80. Only Dr. Kallogjeri (biostatistician) will have a list that links the treatment type (Budesonide or placebo) with the bottle number. The bottle number will correspond to the randomization schedule provided from Dr. Kallogjeri. The subject and the rest of the study team will remain blinded to the randomization assignment. The subject and the rest of the study team will only know what bottle number is being assigned, not which treatment is contained in each bottle. Dr. Kallogjeri is the biostatistician of the study and otherwise is not involved with the participants.

In the event of a Serious Adverse Event determined by the PI to necessitate the breaking of the blind, the intervention assignment will be revealed by Dr. Kallogjeri to the medical staff doctor caring for the patient. In the event Dr. Kallogjeri is unable to be reached in a time needed, to assure the safety of the subject, the blind can be broken by Sara Kukuljan, RN, or Drs. Piccirillo or Schneider and information will be shared with the medical staff assuming care for the patient.

The active drug and placebo will be prepared by Genesis Pharmacy, St. Louis Missouri and delivered to the Clinical Outcomes Office where the products will be stored in a locked cabinet. The cost of sufficient budesonide for the study duration (i.e., 60 budesonide capsules) will be $75 and the cost of sufficient quantity of lactose capsules will be $25.

Budesonide Budesonide is an anti-inflammatory glucocorticoid steroid that is used for a variety of common ailments. Among conditions related to the respiratory tract, budesonide is used as an inhalational drug for the treatment of asthma, COPD, allergic rhinitis, and nasal polyps. The mechanism of action of budesonide is similar to other corticosteroids and includes a wide range of inhibitory activities against multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages and lymphocytes) and mediators (eg, histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic- and non-allergic-mediated inflammation.(AstraZeneca 2000)

Subjects randomized to the budesonide intervention arm will be required to mix 1.0 mg (provided as two capsules containing 0.5 mg budesonide each) budesonide into the sinus rinse bottle and rinse each nasal cavity with one half of the bottle (\~ 4 ounces or \~120 ml) daily. The inert ingredients are: loxasperse powder, which increases solubility and dispersibility of budesonide and is microbiologically safe; mannitol, which is widely used in pharmaceutical products as a capsule diluent; and Xylifos™ powder, which is a proprietary powder excipient used safely in pharmaceutical compounding for nasal nebulization or nasal irrigation.

Placebo The placebo product will contain lactose monohydrate and will be supplied in clear plastic capsules, which are identical to the budesonide capsules. The lactose capsule will only contain lactose as there are no other ingredients.

Concomitant Medications At the time of enrollment, most subjects will be expected to already be using topical nasal steroid medication (ie., fluticasone or Flonase®). Subjects currently using a topical nasal steroid spray will be asked to continue this medication. Topical nasal steroid sprays are indicated therapy for CRS and not considered experimental. Subjects not currently using a topical steroid spray will be asked to not initiate therapy during the duration of the study, unless there is a medical reason to use.

Conditions

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Rhinosinusitis Chronic Eosinophilic Rhinosinusitis Allergic Rhinosinusitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Budesonide

The study intervention will be budesonide powder (0.5 mg/capsule). Subjects will be required to dissolve the contents of two capsules into the 8-ounce (240 ml) NeilMed Sinus Rinse Regular Bottle along with the saline rinse. All subjects will be instructed to irrigate both right and left nasal cavity with one-half of the contents of the nasal rinse once daily.

Each study bottle will contain 60 capsules of Budesonide and will be assigned with a number from 1-80.

Group Type EXPERIMENTAL

Budesonide

Intervention Type DRUG

Participants will undergo 4-week treatment course that includes budesonide powder added to saline rinse.

Saline Alone

Each study bottle will contain 60 capsules of placebo, which is lactose monohydrate and will be supplied in clear plastic capsules identical to the budesonide capsules. Subjects will be required to dissolve the contents of two capsules into the 8-ounce (240 ml) NeilMed Sinus Rinse Regular Bottle along with the saline rinse. All subjects will be instructed to irrigate both right and left nasal cavity with one-half of the contents of the nasal rinse once daily.

Group Type PLACEBO_COMPARATOR

Saline alone

Intervention Type DRUG

Participants will undergo 4-week treatment course that includes lactose (placebo) powder added to saline rinse.

Interventions

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Budesonide

Participants will undergo 4-week treatment course that includes budesonide powder added to saline rinse.

Intervention Type DRUG

Saline alone

Participants will undergo 4-week treatment course that includes lactose (placebo) powder added to saline rinse.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Twelve (12) weeks or longer of two or more of the following signs and symptom consistent with chronic rhinosinusitis (CRS)

• mucopurulent drainage (anterior, posterior, or both), nasal obstruction (congestion),facial pain-pressure-fullness, and decreased sense of smell

AND inflammation documented by one or more of the following findings:

* purulent (not clear) mucus or edema in the middle meatus or ethmoid region,
* polyps in nasal cavity or the middle meatus, and/or
* radiographic imaging showing inflammation of the paranasal sinuses

Exclusion Criteria

* Unable to speak English
* History of comorbid ciliary dyskinesia, cystic fibrosis or any other mucociliary condition
* Dependence on prolonged corticosteroid therapy for comorbid conditions, such as asthma and chronic obstructive pulmonary disease.
* History of oral or systematic antibiotic use in the past 2 weeks
* History of nasal or sinus surgery within past 6 weeks
* History of cerebrospinal fluid leak
* History of allergy to budesonide or other topical steroids
* Pregnant or breast feeding
* Current infection or history of one of the following infections: Tuberculosis (TB) lung infection, or Herpes infection of the eye.
* Baseline SNOT-22 total scores below 9 were excluded due to the inability to achieve a minimally clinically improved difference
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jay F Piccirillo, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Countries

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United States

References

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Report of the Rhinosinusitis Task Force Committee Meeting. Alexandria, Virginia, August 17, 1996. Otolaryngol Head Neck Surg. 1997 Sep;117(3 Pt 2):S1-68. No abstract available.

Reference Type BACKGROUND
PMID: 9380416 (View on PubMed)

Benninger MS, Ferguson BJ, Hadley JA, Hamilos DL, Jacobs M, Kennedy DW, Lanza DC, Marple BF, Osguthorpe JD, Stankiewicz JA, Anon J, Denneny J, Emanuel I, Levine H. Adult chronic rhinosinusitis: definitions, diagnosis, epidemiology, and pathophysiology. Otolaryngol Head Neck Surg. 2003 Sep;129(3 Suppl):S1-32. doi: 10.1016/s0194-5998(03)01397-4. No abstract available.

Reference Type BACKGROUND
PMID: 12958561 (View on PubMed)

Snidvongs K, Pratt E, Chin D, Sacks R, Earls P, Harvey RJ. Corticosteroid nasal irrigations after endoscopic sinus surgery in the management of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2012 Sep-Oct;2(5):415-21. doi: 10.1002/alr.21047. Epub 2012 May 7.

Reference Type BACKGROUND
PMID: 22566474 (View on PubMed)

Sachanandani NS, Piccirillo JF, Kramper MA, Thawley SE, Vlahiotis A. The effect of nasally administered budesonide respules on adrenal cortex function in patients with chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg. 2009 Mar;135(3):303-7. doi: 10.1001/archoto.2008.555.

Reference Type BACKGROUND
PMID: 19289711 (View on PubMed)

Steinke JW, Payne SC, Tessier ME, Borish LO, Han JK, Borish LC. Pilot study of budesonide inhalant suspension irrigations for chronic eosinophilic sinusitis. J Allergy Clin Immunol. 2009 Dec;124(6):1352-4.e7. doi: 10.1016/j.jaci.2009.09.018. No abstract available.

Reference Type BACKGROUND
PMID: 19910027 (View on PubMed)

Piccirillo JF, Merritt MG Jr, Richards ML. Psychometric and clinimetric validity of the 20-Item Sino-Nasal Outcome Test (SNOT-20). Otolaryngol Head Neck Surg. 2002 Jan;126(1):41-7. doi: 10.1067/mhn.2002.121022.

Reference Type BACKGROUND
PMID: 11821764 (View on PubMed)

Browne JP, Hopkins C, Slack R, Cano SJ. The Sino-Nasal Outcome Test (SNOT): can we make it more clinically meaningful? Otolaryngol Head Neck Surg. 2007 May;136(5):736-41. doi: 10.1016/j.otohns.2007.01.024.

Reference Type BACKGROUND
PMID: 17478207 (View on PubMed)

Tait S, Kallogjeri D, Suko J, Kukuljan S, Schneider J, Piccirillo JF. Effect of Budesonide Added to Large-Volume, Low-pressure Saline Sinus Irrigation for Chronic Rhinosinusitis: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2018 Jul 1;144(7):605-612. doi: 10.1001/jamaoto.2018.0667.

Reference Type DERIVED
PMID: 29879268 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Study Documents

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Document Type: Questionnaire

View Document

Other Identifiers

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201512063

Identifier Type: -

Identifier Source: org_study_id

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