Intranasal Steroids and Oxymetazoline in Allergic Rhinitis

Study Overview
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Brief Summary
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We hypothesize that once daily use of oxymetazoline will not cause significant rhinitis medicamentosa and that the combination of fluticasone furoate plus oxymetazoline leads to faster relief of nasal congestion secondary to perennial allergic rhinitis than the use of fluticasone furoate alone.

Detailed Description
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We performed a 6-week, 4-group, parallel, randomized, double-blind, double-dummy, clinical trial in 60 patients with perennial allergic rhinitis. After an initial screening with an allergy questionnaire and skin puncture testing to confirm an allergic response to a perennial allergen (cat, dog, dust mite, indoor mold), qualified individuals were randomized into 1 of 4 treatment groups. The 4 groups received the following treatments: placebo, OXY (0.05%, 2 puffs in each nostril every evening), FF nasal spray (110 mg per day), and FF nasal spray plus OXY (FF/OXY). All participants received 2 nasal sprays at night, with 1 spray containing FF or its placebo, the other oxymetazoline or its placebo. The nasal sprays were labeled with participant code numbers, and the investigator assigned participants in a sequential randomized fashion to a study code number in blocks of 4. Dropouts were replaced until 60 subjects were randomized. Replacement subjects were assigned the next sequential treatment. Thus, the number of subjects in each group was not exactly 15. Eligible participants completed the Rhinitis Quality of Life Questionnaire (RQLQ) and underwent measurement of nasal volume by acoustic rhinometry before starting the study. Participants were instructed to keep a diary of daily symptoms, nasal peak inspiratory flow (NPIF) meter readings, and medication use during the study; no rescue medications were allowed. The severity of sneezing, rhinorrhea, nasal congestion, and other symptoms was recorded in the morning (reflective of symptoms overnight) and evening (reflective of daytime symptoms) on a 0 to 3 scale. Intake of the study medication was performed once daily, at night, after recording of symptoms and NPIF values. Subjects returned to the nasal laboratory every 2 weeks for a total of 4 weeks for review of the symptom diaries, replacement of medications, performance of acoustic rhinometry, and completion of the RQLQ. After the fourth week, participants stopped treatment, returned medication, and continued with the clinical trial for 2 additional weeks. During this time, they maintained symptom diaries and NPIF measurements twice daily. At the end of the 2-week period, participants returned to the nasal laboratory to perform a final acoustic rhinometry, complete an RQLQ survey, and return the diaries.

Official Title
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A Combination of Intranasal Steroid/Oxymetazoline Leads to Faster Relief of Nasal Congestion Without Inducing Rhinitis Medicamentosa

Conditions
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Allergic Rhinitis

Intervention / Treatment
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* Drug: Fluticasone furoate
* Drug: Placebo Fluticasone furoate
* Drug: Oxymetazoline
* Drug: Placebo Oxymetazoline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between 18 and 55 years of age. History of perennial allergic rhinitis. Positive skin test to dust mite, dog, cat or indoor mold antigen. And a combined nasal morning and evening score of ≥4 for nasal congestion in the day preceding entry Exclusion Criteria: Physical signs or symptoms suggestive of renal, hepatic or cardiovascular disease. Pregnant or lactating women. Subjects treated with systemic steroids during the previous 30 days. Subjects treated with topical (inhaled, intranasal or intraocular) steroids, Nasalcrom or Opticrom during the previous 30 days. Subjects treated with oral antihistamine/decongestants during the previous seven days. Subjects treated with topical (intranasal or intraocular) antihistamine/decongestants during the previous 3 days. Subjects treated with immunotherapy and are escalating their dose. Subjects on chronic anti-asthma medications. Subjects with polyps in the nose or a significantly displaced septum. Upper respiratory infection within 14 days of study start.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo FF + Placebo OXY<br>Placebo Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm | Drug: Placebo Fluticasone furoate<br>* 2 puffs of each nasal spray in each nostril in the pm<br>Drug: Placebo Oxymetazoline<br>* 2 puffs of each nasal spray in each nostril in the pm<br>|
| Active Comparator: FF + Placebo OXY<br>Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm | Drug: Fluticasone furoate<br>* 2 puffs of each nasal spray in each nostril in the pm<br>* Other names: Veramyst;Drug: Placebo Oxymetazoline<br>* 2 puffs of each nasal spray in each nostril in the pm<br>|
| Active Comparator: Placebo FF + OXY<br>Placebo Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm | Drug: Placebo Fluticasone furoate<br>* 2 puffs of each nasal spray in each nostril in the pm<br>Drug: Oxymetazoline<br>* 2 puffs of each nasal spray in each nostril in the pm<br>* Other names: Oxymetazoline hydrochloride;|
| Active Comparator: FF + OXY<br>Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm | Drug: Fluticasone furoate<br>* 2 puffs of each nasal spray in each nostril in the pm<br>* Other names: Veramyst;Drug: Oxymetazoline<br>* 2 puffs of each nasal spray in each nostril in the pm<br>* Other names: Oxymetazoline hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Nasal Congestion Symptom Score | The severity of nasal congestion was recorded in the morning (reflective of symptoms overnight) and evening (reflective of daytime symptoms) on a 0 to 3 scale. The total nasal congestion symptom score was obtained by adding the symptoms obtained on all 28 days of treatment. Values for this outcome are in the range of 0 to 168 (i.e., 6 x 28). Congestion scores increase with congestion severity (i.e., higher numbers correspond to worse congestion). | 28 days of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RQLQ Score [Baseline] | The Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) has 28 questions and focusses on 7 domains that may be significantly impaired in participants with seasonal allergic rhinoconjunctivitis: sleep impairment, non-nasal symptoms, practical problems, nasal symptoms, eye symptoms, activity limitations, and emotional difficulty. The RQLQ score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains. RQLQ scores range from 0-6, with a higher score indicating more significant impairment. | assessed at baseline | 
| RQLQ Score [2 Weeks] | The Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) has 28 questions and focusses on 7 domains that may be significantly impaired in participants with seasonal allergic rhinoconjunctivitis: sleep impairment, non-nasal symptoms, practical problems, nasal symptoms, eye symptoms, activity limitations, and emotional difficulty. The RQLQ score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains. RQLQ scores range from 0-6, with a higher score indicating more significant impairment. | assessed 2 weeks after initiation of treatment regimen | 
| RQLQ Score [4 Weeks] | The Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) has 28 questions and focusses on 7 domains that may be significantly impaired in participants with seasonal allergic rhinoconjunctivitis: sleep impairment, non-nasal symptoms, practical problems, nasal symptoms, eye symptoms, activity limitations, and emotional difficulty. The RQLQ score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains. RQLQ scores range from 0-6, with a higher score indicating more significant impairment. | assessed 4 weeks after initiation of treatment regimen | 
| RQLQ Score [6 Weeks] | The Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) has 28 questions and focusses on 7 domains that may be significantly impaired in participants with seasonal allergic rhinoconjunctivitis: sleep impairment, non-nasal symptoms, practical problems, nasal symptoms, eye symptoms, activity limitations, and emotional difficulty. The RQLQ score is the mean of all 28 responses and the individual domain scores are the means of the items in those domains. RQLQ scores range from 0-6, with a higher score indicating more significant impairment. | assessed 6 weeks after initiation of treatment regimen | 
| Total NPIF | Nasal peak inspiratory flow (NPIF) is a physiological measure of nasal airflow which is particularly sensitive to nasal valve collapse. NPIF was measured objectively in liters per minute with an In-Check Peak Inspiratory FlowMeter (Ferraris Medical Inc, Orchard Park, NY). Subjects obtained 3 readings every morning and every evening and recorded the best flow measured. The morning and evening NPIF measurements were summed for days 2 through 28 of the treatment cycle, yielding the total NPIF outcome measure. NPIF scores increase with air flow quality (i.e., higher NPIF values are indicative of better nasal air flow). | days 2 through 28 of the treatment cycle |