The Effectiveness of Nasal Corticosteroids Versus Placebo in Nasal Obstruction in Patients With Nasal Septal Deviation

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02877485
• Collaborator: (none)
• Enrollment: 42
• Location: 1
• Arms: 2
• Actual Duration (Months): 36.4
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this project is to determine if intranasal corticosteroids have an effect on nasal obstruction in patients with nasal septal deviation.

Condition or Disease	Intervention/Treatment	Phase
Nasal Obstruction	Drug: Triamcinolone Acetonide; Drug: Ayr saline nasal mist	Phase 4

Detailed Description

Participants were identified at their initial visit to the Stanford Facial Plastic and Reconstructive Surgery Clinic, an academic referral center, in consultation for nasal obstruction. If eligible and interested in participating, patients provided written informed consent prior to randomization.

Eligible participants were patients over the age of 18 years of age with the presence of nasal septal deviation as identified by physical examination, as well as a baseline NOSE score of 35 or greater. Exclusion criteria included a history of nasal or septal surgery, use of intranasal steroids in the three months preceding enrollment, use of systemic steroids in the six months preceding enrollment, and pregnancy or active breastfeeding at the time of enrollment. In order to maximize generalizability of the study, no medications other than systemic and intranasal steroids were used as exclusion criteria.

All study participants received 6 weeks of therapy with an intranasal steroid spray, Nasacort (Chattem Inc), which consists of the steroid triamcinolone acetonide, as well as 6 weeks of placebo with Ayr saline spray (B.F. Ascher). These two study drugs were packaged identically by a local pharmacist and labelled Drug A and Drug B. Nasacort was selected as the intranasal steroid following pharmacist consultation, as this intranasal steroid is less scented than others and therefore was less likely to be distinguishable from the placebo to participants. Participants were instructed to use both drugs as follows: 1 spray per nostril twice a day. Researchers, statistical analysts, and study participants were blinded to the identity of the two drugs until the conclusion of the study. A duration of 6 weeks per drug was selected based on the most commonly observed insurance requirements seen in our practice. Following unblinding, it was determined that Drug A was the placebo, the saline spray, and Drug B was the test drug, the nasal steroid.

Following completion of both study drugs, patients were offered surgical intervention. If interested and medically cleared for surgery, patients underwent surgery. All surgeries were performed by the senior author and included open septorhinoplasty to address septal deviation, with repair of nasal valve stenosis and inferior turbinate reduction performed in some patients as deemed necessary by the senior author.

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effectiveness of Nasal Corticosteroids Versus Placebo in Nasal Obstruction in Patients With Nasal Septal Deviation
• Actual Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Aug 15, 2019
• Actual Study Completion Date: Aug 15, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Triamcinolone acetonide then Ayr spray This study arm will start with 6 weeks of therapy with the intranasal steroid, followed by 6 weeks of therapy with a placebo, with a two week washout period in between treatments.	Drug: Triamcinolone Acetonide; 2 sprays sprayed to both nostrils daily for 42 days.; Other Names: Nasacort ; Drug: Ayr saline nasal mist; 110mcg (2 sprays) sprayed to both nostrils daily for 42 days.
Active Comparator: Ayr spray then triamcinolone acetonide This study arm will start with 6 weeks of placebo, followed by 6 weeks of therapy with the intranasal steroid, with a two week washout period in between treatments.	Drug: Triamcinolone Acetonide; 2 sprays sprayed to both nostrils daily for 42 days.; Other Names: Nasacort ; Drug: Ayr saline nasal mist; 110mcg (2 sprays) sprayed to both nostrils daily for 42 days.

Outcome Measures

Primary Outcome Measures

1. Nasal Obstruction as Measured by Nasal Obstruction Symptom Evaluation (NOSE) Scores Following Therapy With Treatment (Triamcinolone Acetonide) and Placebo (Ayr Saline Spray) [Pre-spray NOSE score - 6 weeks Post spray NOSE score- 2 weeks washout - Pre spray Pre-spray NOSE score - 6 weeks Post spray NOSE score]

   Nasal Obstruction Symptom Evaluation (NOSE) scale: A quality of life (QOL) instrument developed to assess nasal obstruction symptoms in patients undergoing septoplasty. It consists of a 5-item questionnaire, scored on a 5-point (0-4) Likert scale. The raw score ranges from 0-20, which is scaled to a score of 0-100 by multiplying the raw score by 5, where '0' represents 'no problem' and, and '100' represent 'worst problem.'

Secondary Outcome Measures

1. Nasal Obstruction Symptom Evaluation (NOSE) Score Following Surgery in Subset of Patients Who Elect to Undergo Surgery. [Postoperative time interval (months): 1-2 , 3-5 , 6-9, 9-12, >12.]

   Nasal Obstruction Symptom Evaluation (NOSE) scale: A quality of life (QOL) instrument developed to assess nasal obstruction symptoms in patients undergoing septoplasty. It consists of a 5-item questionnaire, scored on a 5-point (0-4) Likert scale. The raw score ranges from 0-20, which is scaled to a score of 0-100 by multiplying the raw score by 5, where '0' represents 'no problem' and, and '100' represent 'worst problem.'

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age greater than 18

• NOSE score greater than 55

• Nasal septal deviation on exam

Exclusion Criteria:

• Intranasal steroid use within the last three months

• Current systemic steroid use

• Prior septal surgery

• Individuals who are pregnant or actively breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Hospital and Clinics	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Sam P Most, MD, Stanford University

Study Documents (Full-Text)

• Informed Consent Form - May 24, 2019
• Study Protocol and Statistical Analysis Plan - Apr 13, 2016

More Information

Publications

• Lipan MJ, Most SP. Development of a severity classification system for subjective nasal obstruction. JAMA Facial Plast Surg. 2013 Sep-Oct;15(5):358-61. doi: 10.1001/jamafacial.2013.344.
• Sedaghat AR, Busaba NY, Cunningham MJ, Kieff DA. Clinical assessment is an accurate predictor of which patients will need septoplasty. Laryngoscope. 2013 Jan;123(1):48-52. doi: 10.1002/lary.23683. Epub 2012 Nov 20.
• Stewart MG, Witsell DL, Smith TL, Weaver EM, Yueh B, Hannley MT. Development and validation of the Nasal Obstruction Symptom Evaluation (NOSE) scale. Otolaryngol Head Neck Surg. 2004 Feb;130(2):157-63.
• Teti VP, Akdagli S, Most SP. Cost-effectiveness of Corticosteroid Nasal Spray vs Surgical Therapy in Patients With Severe to Extreme Anatomical Nasal Obstruction. JAMA Facial Plast Surg. 2016 May 1;18(3):165-70. doi: 10.1001/jamafacial.2015.2039.

• Responsible Party: Sam P. Most, Chief, Division of Facial Plastic and Reconstructive Surgery, Stanford University
• ClinicalTrials.gov Identifier: NCT02877485
• Other Study ID Numbers: IRB-36535
• First Posted: Aug 24, 2016
• Last Update Posted: Aug 13, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Nasal Obstruction; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate

Study Results

Participant Flow

Arm/Group Title	Triamcinolone Acetonide Then Ayr Spray	Ayr Spray Then Triamcinolone Acetonide
Arm/Group Description	This study arm will start with 6 weeks of therapy with the intranasal steroid, followed by 6 weeks of therapy with a placebo, with a two week washout period in between treatments. Triamcinolone Acetonide: 2 sprays sprayed to both nostrils daily for 42 days. Ayr saline nasal mist: 110mcg (2 sprays) sprayed to both nostrils daily for 42 days.	This study arm will start with 6 weeks of placebo, followed by 6 weeks of therapy with the intranasal steroid, with a two week washout period in between treatments. Triamcinolone Acetonide: 2 sprays sprayed to both nostrils daily for 42 days. Ayr saline nasal mist: 110mcg (2 sprays) sprayed to both nostrils daily for 42 days.
Period Title: Overall Study
STARTED	22	20
COMPLETED	22	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Triamcinolone Acetonide Then Ayr Spray	Ayr Spray Then Triamcinolone Acetonide	Total
Arm/Group Description	This study arm will start with 6 weeks of therapy with the intranasal steroid, followed by 6 weeks of therapy with a placebo, with a two week washout period in between treatments. Triamcinolone Acetonide: 2 sprays sprayed to both nostrils daily for 42 days. Ayr saline nasal mist: 110mcg (2 sprays) sprayed to both nostrils daily for 42 days.	This study arm will start with 6 weeks of placebo, followed by 6 weeks of therapy with the intranasal steroid, with a two week washout period in between treatments. Triamcinolone Acetonide: 2 sprays sprayed to both nostrils daily for 42 days. Ayr saline nasal mist: 110mcg (2 sprays) sprayed to both nostrils daily for 42 days.	Total of all reporting groups
Overall Participants	22	20	42
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	21 95.5%	20 100%	41 97.6%
>=65 years	1 4.5%	0 0%	1 2.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.5 (10.1)	33.7 (14.4)	33.0 (12.2)
Sex: Female, Male (Count of Participants)
Female	11 50%	5 25%	16 38.1%
Male	11 50%	15 75%	26 61.9%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	22 100%	20 100%	42 100%

Outcome Measures

1. Primary Outcome

Title	Nasal Obstruction as Measured by Nasal Obstruction Symptom Evaluation (NOSE) Scores Following Therapy With Treatment (Triamcinolone Acetonide) and Placebo (Ayr Saline Spray)
Description	Nasal Obstruction Symptom Evaluation (NOSE) scale: A quality of life (QOL) instrument developed to assess nasal obstruction symptoms in patients undergoing septoplasty. It consists of a 5-item questionnaire, scored on a 5-point (0-4) Likert scale. The raw score ranges from 0-20, which is scaled to a score of 0-100 by multiplying the raw score by 5, where '0' represents 'no problem' and, and '100' represent 'worst problem.'
Time Frame	Pre-spray NOSE score - 6 weeks Post spray NOSE score- 2 weeks washout - Pre spray Pre-spray NOSE score - 6 weeks Post spray NOSE score

Outcome Measure Data

Analysis Population Description

Patients requiring nasal surgery for nasal breathing complaints, nasal cosmesis or both.

Arm/Group Title	Triamcinolone Acetonide Then Ayr Spray	Ayr Spray Then Triamcinolone Acetonide
Arm/Group Description	This study arm will start with 6 weeks of therapy with the intranasal steroid, followed by 6 weeks of therapy with a placebo, with a two week washout period in between treatments. Triamcinolone Acetonide: 2 sprays sprayed to both nostrils daily for 42 days. Ayr saline nasal mist: 110mcg (2 sprays) sprayed to both nostrils daily for 42 days.	This study arm will start with 6 weeks of placebo, followed by 6 weeks of therapy with the intranasal steroid, with a two week washout period in between treatments. Triamcinolone Acetonide: 2 sprays sprayed to both nostrils daily for 42 days. Ayr saline nasal mist: 110mcg (2 sprays) sprayed to both nostrils daily for 42 days.
Measure Participants	22	20
Baseline: Pre - spray 1 NOSE score	69.1 (20.4)	68.5 (18)
Post - spray 1 / pre- spray 2 NOSE score	65.2 (20.7)	65.8 (20.2)
Post - spray 2 NOSE score	64.1 (20.6)	61.5 (21.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Triamcinolone Acetonide Then Ayr Spray, Ayr Spray Then Triamcinolone Acetonide
	Comments	1) H0: mean change in NOSE score from baseline after in study group 1 = mean change in NOSE score from baseline in study group 2 Power calculation: To detect a 20% difference in NOSE scores with 80% power and a 2-sided alpha level of 0.05 required 20 participants per study group, for a total of 40 participants.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7
	Comments	Statistical Tests: Independent t-test to assess differences in mean change in NOSE scores when comparing the two study groups, and p<0.05 deemed statistically significant
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; -6.0 to 8.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Change in Mean NOSE score from baseline to post saline versus change in NOSE score from baseline to post intranasal steroid.

2. Secondary Outcome

Title	Nasal Obstruction Symptom Evaluation (NOSE) Score Following Surgery in Subset of Patients Who Elect to Undergo Surgery.
Description	Nasal Obstruction Symptom Evaluation (NOSE) scale: A quality of life (QOL) instrument developed to assess nasal obstruction symptoms in patients undergoing septoplasty. It consists of a 5-item questionnaire, scored on a 5-point (0-4) Likert scale. The raw score ranges from 0-20, which is scaled to a score of 0-100 by multiplying the raw score by 5, where '0' represents 'no problem' and, and '100' represent 'worst problem.'
Time Frame	Postoperative time interval (months): 1-2 , 3-5 , 6-9, 9-12, >12.

Outcome Measure Data

Analysis Population Description

Pooled analysis of 35 participants who underwent surgery. Paired t-tests were used to assess differences in mean change in NOSE scores at five post-operative time points compared to baseline NOSE scores.

Arm/Group Title	Surgery Patients
Arm/Group Description	Participants who underwent surgery
Measure Participants	35
Baseline NOSE score	70 (18.9)
Postoperative period: 1-2 months	16.2 (20.5)
Postoperative period:3-5 months	17.6 (16.5)
Postoperative period:6-9 months	17.2 (19.8)
Postoperative period: 9-12 months	22.2 (24.9)
Postoperative period: >12 months	20 (18.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Triamcinolone Acetonide Then Ayr Spray
	Comments	H0: Mean pre- treatment baseline patient NOSE score = Mean post- treatment baseline patient NOSE score.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Paired t-tests to assess differences in mean NOSE score when the treatment groups were combined (saline arm+ steroid arm) at five post-operative time intervals compared to the combined preoperative baseline scores. Significance at p<0.05.
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-50
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 27.6
	Estimation Comments

Adverse Events

Time Frame	6 weeks after start of treatment (after drug spray 1). 14 weeks after start of treatment (after drug spray 2)
Adverse Event Reporting Description	No adverse events to report
Arm/Group Title	Triamcinolone Acetonide		Ayr Spray
Arm/Group Description	Triamcinolone Acetonide: 2 sprays sprayed to both nostrils daily for 42 days.		Ayr saline nasal mist: 110mcg (2 sprays) sprayed to both nostrils daily for 42 days.
All Cause Mortality
	Triamcinolone Acetonide		Ayr Spray
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/20 (0%)
Serious Adverse Events
	Triamcinolone Acetonide		Ayr Spray
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Triamcinolone Acetonide		Ayr Spray
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/20 (0%)

Limitations/Caveats

The presence and degree of inferior turbinate hypertrophy, the presence of allergic rhinitis, chronic sinusitis, and other forms of nasal mucosal edema, were not assessed or included in analysis.

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.