Intranasal Steroids and Oxymetazoline in Allergic Rhinitis

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT00584987
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 64
• Location: 1
• Arms: 4
• Duration (Months): 25
• Patients Per Site Per Month: 2.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Allergic Rhinitis	Drug: Fluticasone furoate; Drug: Placebo Fluticasone furoate; Drug: Oxymetazoline; Drug: Placebo Oxymetazoline	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Combination of Intranasal Steroid/Oxymetazoline Leads to Faster Relief of Nasal Congestion Without Inducing Rhinitis Medicamentosa
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo FF + Placebo OXY Placebo Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Drug: Placebo Fluticasone furoate; 2 puffs of each nasal spray in each nostril in the pm; Drug: Placebo Oxymetazoline; 2 puffs of each nasal spray in each nostril in the pm
Active Comparator: FF + Placebo OXY Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Drug: Fluticasone furoate; 2 puffs of each nasal spray in each nostril in the pm; Other Names: Veramyst ; Drug: Placebo Oxymetazoline; 2 puffs of each nasal spray in each nostril in the pm
Active Comparator: Placebo FF + OXY Placebo Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Drug: Placebo Fluticasone furoate; 2 puffs of each nasal spray in each nostril in the pm; Drug: Oxymetazoline; 2 puffs of each nasal spray in each nostril in the pm; Other Names: Oxymetazoline hydrochloride
Active Comparator: FF + OXY Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Drug: Fluticasone furoate; 2 puffs of each nasal spray in each nostril in the pm; Other Names: Veramyst ; Drug: Oxymetazoline; 2 puffs of each nasal spray in each nostril in the pm; Other Names: Oxymetazoline hydrochloride

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago
• GlaxoSmithKline

Investigators

• Principal Investigator: Robert M Naclerio, MD, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert Naclerio, MD, University of Chicago
• ClinicalTrials.gov Identifier: NCT00584987
• Other Study ID Numbers: 15059B
• First Posted: Jan 2, 2008
• Last Update Posted: Dec 17, 2013
• Last Verified: Oct 1, 2013

• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Fluticasone; Xhance; Phenylephrine; Oxymetazoline

Study Results

Participant Flow

Arm/Group Title	PL FF + PL OXY	FF + PL OXY	PL FF + OXY	FF + OXY
Arm/Group Description	Placebo Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Placebo Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm
Period Title: Overall Study
STARTED	15	16	17	16
COMPLETED	14	15	16	15
NOT COMPLETED	1	1	1	1

Baseline Characteristics

Arm/Group Title	Placebo FF + Placebo OXY	FF + Placebo OXY	Placebo FF + OXY	FF + OXY	Total
Arm/Group Description	Placebo Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Placebo Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Total of all reporting groups
Overall Participants	15	16	17	16	64
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.6 (11)	31.7 (9.5)	26.6 (5.2)	28.6 (8.7)	28.8 (8.5)
Sex: Female, Male (Count of Participants)
Female	10 66.7%	12 75%	10 58.8%	9 56.3%	41 64.1%
Male	5 33.3%	4 25%	7 41.2%	7 43.8%	23 35.9%

Outcome Measures

1. Primary Outcome

Title	Total Nasal Congestion Symptom Score
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo FF + Placebo OXY	FF + Placebo OXY	Placebo FF + OXY	FF + OXY
Arm/Group Description	Placebo Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Placebo Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm
Measure Participants	14	15	16	15
Median (Full Range) [units on a scale]	94	70	75	68

2. Secondary Outcome

Title	RQLQ Score [Baseline]
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo FF + Placebo OXY	FF + Placebo OXY	Placebo FF + OXY	FF + OXY
Arm/Group Description	Placebo Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Placebo Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm
Measure Participants	14	15	16	15
Mean (Standard Error) [units on a scale]	3.07 (0.28)	3.25 (0.29)	2.99 (0.28)	2.60 (0.22)

3. Secondary Outcome

Title	RQLQ Score [2 Weeks]
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo FF + Placebo OXY	FF + Placebo OXY	Placebo FF + OXY	FF + OXY
Arm/Group Description	Placebo Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Placebo Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm
Measure Participants	14	15	16	15
Mean (Standard Error) [units on a scale]	2.20 (0.26)	2.03 (0.26)	2.11 (0.20)	1.62 (0.24)

4. Secondary Outcome

Title	RQLQ Score [4 Weeks]
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo FF + Placebo OXY	FF + Placebo OXY	Placebo FF + OXY	FF + OXY
Arm/Group Description	Placebo Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Placebo Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm
Measure Participants	14	15	16	15
Mean (Standard Error) [units on a scale]	1.75 (0.24)	1.37 (0.24)	1.85 (0.20)	1.26 (0.22)

5. Secondary Outcome

Title	RQLQ Score [6 Weeks]
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo FF + Placebo OXY	FF + Placebo OXY	Placebo FF + OXY	FF + OXY
Arm/Group Description	Placebo Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Placebo Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm
Measure Participants	14	15	16	15
Mean (Standard Error) [units on a scale]	1.85 (0.25)	1.83 (0.33)	2.03 (0.27)	1.55 (0.19)

6. Secondary Outcome

Title	Total NPIF
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo FF + Placebo OXY	FF + Placebo OXY	Placebo FF + OXY	FF + OXY
Arm/Group Description	Placebo Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Placebo Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm	Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm
Measure Participants	14	15	16	15
Median (Full Range) [liters per minute]	5240	5680	4485.5	5520

Adverse Events

Time Frame	Subjects were monitored for adverse events 2 weeks after treatment as outlined in the protocol. No subjects presented with adverse events after the official follow-up period concluded.
Arm/Group Title	Placebo FF + Placebo OXY		FF + Placebo OXY		Placebo FF + OXY		FF + OXY
Arm/Group Description	Placebo Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm		Fluticasone furoate + Placebo Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm		Placebo Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm		Fluticasone furoate + Oxymetazoline, 2 puffs of each nasal spray in each nostril in the pm
All Cause Mortality
	Placebo FF + Placebo OXY		FF + Placebo OXY		Placebo FF + OXY		FF + OXY
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo FF + Placebo OXY		FF + Placebo OXY		Placebo FF + OXY		FF + OXY
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/16 (0%)		0/17 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Placebo FF + Placebo OXY		FF + Placebo OXY		Placebo FF + OXY		FF + OXY
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/15 (13.3%)		4/16 (25%)		2/17 (11.8%)		2/16 (12.5%)
General disorders
Headaches	2/15 (13.3%)		4/16 (25%)		2/17 (11.8%)		2/16 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.