The Impact Of The Addition Of Budesonide To Low-Pressure, High-Volume Saline Sinus Irrigation For Chronic Rhinosinusitis
Condition: Rhinosinusitis; Chronic Eosinophilic Rhinosinusitis; Allergic Rhinosinusitis
MeSH terms: Sinusitis; Rhinitis, Allergic
Study type: Interventional
Phase: Phase 4

Summary: 
      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: 
      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.
    

Intervention name(s): Budesonide; Saline alone
Intervention type(s): Drug; Drug
Intervention description(s): Participants will undergo 4-week treatment course that includes budesonide powder added to saline rinse.; Participants will undergo 4-week treatment course that includes lactose (placebo) powder added to saline rinse.
Intervention MeSH terms: Budesonide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: sinusitis; rhinosinusitis; rhinitis; nasal lavage