Allergic Rhinitis
Conditions
Brief summary
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
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.
Interventions
DRUGPlacebo Oxymetazoline
2 puffs of each nasal spray in each nostril in the pm
DRUGFluticasone furoate
2 puffs of each nasal spray in each nostril in the pm
DRUGPlacebo Fluticasone furoate
2 puffs of each nasal spray in each nostril in the pm
DRUGOxymetazoline
2 puffs of each nasal spray in each nostril in the pm
Sponsors
GlaxoSmithKline
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Males and females between 18 and 55 years of age. 2. History of perennial allergic rhinitis. 3. Positive skin test to dust mite, dog, cat or indoor mold antigen. 4. And a combined nasal morning and evening score of ≥4 for nasal congestion in the day preceding entry
Exclusion criteria
1. Physical signs or symptoms suggestive of renal, hepatic or cardiovascular disease. 2. Pregnant or lactating women. 3. Subjects treated with systemic steroids during the previous 30 days. 4. Subjects treated with topical (inhaled, intranasal or intraocular) steroids, Nasalcrom or Opticrom during the previous 30 days. 5. Subjects treated with oral antihistamine/decongestants during the previous seven days. 6. Subjects treated with topical (intranasal or intraocular) antihistamine/decongestants during the previous 3 days. 7. Subjects treated with immunotherapy and are escalating their dose. 8. Subjects on chronic anti-asthma medications. 9. Subjects with polyps in the nose or a significantly displaced septum. 10. Upper respiratory infection within 14 days of study start.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Nasal Congestion Symptom Score | 28 days of treatment | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RQLQ Score [Baseline] | assessed at 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. |
| RQLQ Score [2 Weeks] | assessed 2 weeks after initiation of treatment regimen | 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. |
| RQLQ Score [4 Weeks] | assessed 4 weeks after initiation of treatment regimen | 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. |
| RQLQ Score [6 Weeks] | assessed 6 weeks after initiation of treatment regimen | 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. |
| Total NPIF | days 2 through 28 of the treatment cycle | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo FF + Placebo OXY Placebo Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm | 15 |
| FF + Placebo OXY Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm | 16 |
| Placebo FF + OXY Placebo Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm | 17 |
| FF + OXY Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm | 16 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo FF + Placebo OXY | FF + Placebo OXY | Placebo FF + OXY | FF + OXY | Total |
|---|---|---|---|---|---|
| Age Continuous | 29.6 years STANDARD_DEVIATION 11 | 31.7 years STANDARD_DEVIATION 9.5 | 26.6 years STANDARD_DEVIATION 5.2 | 28.6 years STANDARD_DEVIATION 8.7 | 28.8 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 10 Participants | 12 Participants | 10 Participants | 9 Participants | 41 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 7 Participants | 7 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 15 | 4 / 16 | 2 / 17 | 2 / 16 |
| serious Total, serious adverse events | 0 / 15 | 0 / 16 | 0 / 17 | 0 / 16 |
Outcome results
Primary
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).
Time frame: 28 days of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo FF + Placebo OXY | Total Nasal Congestion Symptom Score | 94 units on a scale |
| FF + Placebo OXY | Total Nasal Congestion Symptom Score | 70 units on a scale |
| Placebo FF + OXY | Total Nasal Congestion Symptom Score | 75 units on a scale |
| FF + OXY | Total Nasal Congestion Symptom Score | 68 units on a scale |
Secondary
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.
Time frame: assessed 2 weeks after initiation of treatment regimen
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo FF + Placebo OXY | RQLQ Score [2 Weeks] | 2.20 units on a scale | Standard Error 0.26 |
| FF + Placebo OXY | RQLQ Score [2 Weeks] | 2.03 units on a scale | Standard Error 0.26 |
| Placebo FF + OXY | RQLQ Score [2 Weeks] | 2.11 units on a scale | Standard Error 0.2 |
| FF + OXY | RQLQ Score [2 Weeks] | 1.62 units on a scale | Standard Error 0.24 |
Secondary
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.
Time frame: assessed 4 weeks after initiation of treatment regimen
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo FF + Placebo OXY | RQLQ Score [4 Weeks] | 1.75 units on a scale | Standard Error 0.24 |
| FF + Placebo OXY | RQLQ Score [4 Weeks] | 1.37 units on a scale | Standard Error 0.24 |
| Placebo FF + OXY | RQLQ Score [4 Weeks] | 1.85 units on a scale | Standard Error 0.2 |
| FF + OXY | RQLQ Score [4 Weeks] | 1.26 units on a scale | Standard Error 0.22 |
Secondary
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.
Time frame: assessed 6 weeks after initiation of treatment regimen
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo FF + Placebo OXY | RQLQ Score [6 Weeks] | 1.85 units on a scale | Standard Error 0.25 |
| FF + Placebo OXY | RQLQ Score [6 Weeks] | 1.83 units on a scale | Standard Error 0.33 |
| Placebo FF + OXY | RQLQ Score [6 Weeks] | 2.03 units on a scale | Standard Error 0.27 |
| FF + OXY | RQLQ Score [6 Weeks] | 1.55 units on a scale | Standard Error 0.19 |
Secondary
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.
Time frame: assessed at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo FF + Placebo OXY | RQLQ Score [Baseline] | 3.07 units on a scale | Standard Error 0.28 |
| FF + Placebo OXY | RQLQ Score [Baseline] | 3.25 units on a scale | Standard Error 0.29 |
| Placebo FF + OXY | RQLQ Score [Baseline] | 2.99 units on a scale | Standard Error 0.28 |
| FF + OXY | RQLQ Score [Baseline] | 2.60 units on a scale | Standard Error 0.22 |
Secondary
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).
Time frame: days 2 through 28 of the treatment cycle
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo FF + Placebo OXY | Total NPIF | 5240 liters per minute |
| FF + Placebo OXY | Total NPIF | 5680 liters per minute |
| Placebo FF + OXY | Total NPIF | 4485.5 liters per minute |
| FF + OXY | Total NPIF | 5520 liters per minute |