PND: Efficacy of Lansoprazole in Chronic Post Nasal Drip

• Sponsor: Vanderbilt University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00335283
• Collaborator: TAP Pharmaceutical Products Inc. (Industry)
• Enrollment: 75
• Location: 1
• Arms: 2
• Duration (Months): 28
• Patients Per Site Per Month: 2.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether aggressive acid suppression with Lansoprazole is effective in the treatment of post nasal drip, and also assess the predictors of response based on clinical and physiologic parameters.

Condition or Disease	Intervention/Treatment	Phase
Larynx Disease	Drug: Lansoprazole Tablet; Procedure: PH and impedence testing; Procedure: manometry; Drug: lansoprazole; Drug: placebo	Phase 3

Detailed Description

Postnasal drip (PND) is a common complaint that brings patients to the attention of their primary care physicians. It is also one of the most common reasons for patients to seek care from otolaryngologists. Traditionally, PND has been considered and treated as a symptom of sinonasal pathology. It has also been shown, along with Gastroesophageal reflux disease (GERD) and asthma, to be a major contributor to the development of chronic cough. PND refractory to treatment aimed at sinonasal disease is sometimes treated with anti-GERD therapy. This treatment modality is based on clinical experience. To date, there are no studies in the literature to support a causal relationship between PND and extraesophageal reflux (EER). In a case control study of patients with and without esophagitis El-Serag et al reported a significant association (odds ratio 1.6, 95%CI 1.4-1.8) between sinusitis and GERD. A later study by Ulualp et al in 11 CT confirmed cases of chronic sinusitis resistant to therapy with conventional sinus therapies they found a significantly higher prevalence of hypopharyngeal acid exposure in the sinusitis group than controls. Recently, in an open label prospective pilot trial, DiBaise et al treated 11 patients with sinusitis and 19 GERD patients with omeprazole 20mg bid for 3-months. 9/11 sinusitis patients were found to have GERD by pH monitoring and there was moderate (25-89%) improvement in the sinus symptoms in the omeprazole treated group. However, there are currently no placebo-controlled trials assessing efficacy of PPI's in patients with PND.

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Placebo-Controlled Trial of BID Lansoprazole in Isolated Chronic Post Nasal Drip
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lansoprazole	Drug: Lansoprazole Tablet; 40 mg bid x 16 weeks; Other Names: prevacid ; Procedure: PH and impedence testing; 24 hour ph monitoring; Procedure: manometry; done prior to pH probe to measure length of esophagus; Drug: lansoprazole; 40mg bid
Placebo Comparator: Sugar Pill	Procedure: PH and impedence testing; 24 hour ph monitoring; Procedure: manometry; done prior to pH probe to measure length of esophagus; Drug: placebo; one tablet bid

Outcome Measures

Primary Outcome Measures

1. Post Nasal Drainage Symptom Response [8 and 16 weeks]

   The primary outcome measure was postnasal drainage symptom response measured by using a visual analogue scale. At 8 and 16 weeks, a horizontal symptoms scale from 0% (no change) to 100% (symptoms completely resolved) was presented to participants to assess improvement in postnasal drainage symptoms.

Secondary Outcome Measures

1. Rhinosinusitis Outcome Measure(RSOM-31) [Baseline, 8 weeks, and 16 weeks]

   RSOM-31 includes 31 questions combined into a total score ranging from 0 to 155 with higher scores representing greater disease burden. Values are based on patient report.

2. Sino Nasal Outcome Test (SNOT-20) [Baseline, 8 weeks and 16 weeks]

   SNOT-20 includes 20 questions combined into a total score ranging from 0 to 100 with higher numbers representing greater rhinosinusitis health burden and represents patient-reported symptom severity.

3. Quality of Life Questionnaire (QOLRAD) [Baseline, 8 weeks and 16 weeks]

   The patient-reported QOLRAD consists of 25 questions combined into a total score ranging from 25 to 175 with higher numbers representing better quality of life.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Negative RAST inhalant allergy panel OR negative skin testing (Group A)

• Positive RAST or Positive skin testing AND insufficient response to all of the following: (Group B)

• Allergen avoidance

• Topical nasal steroids

• Allergy shots if indicated

• Antihistamines

• Negative CT sinuses (coronal)

• < 4mm of mucosal thickening and < 3 sinus sites

• Absence of air-fluid levels

• Negative anterior rhinoscopy

• Absence of pus, crusts on mucosal surfaces

Exclusion Criteria:

• Age < 18

• Pregnancy, confirmed by urine pregnancy test at day of randomization

• Ciliary dyskinesia

• Immune deficiency

• Cystic fibrosis

• Diagnosis of acute sinusitis or chronic RS (AAO-HNS)

• Active use of topical decongestant

• Use of PPI within the last 30 days

• Previous fundoplication

• Uncontrolled thyroid disease

• Isolated chronic cough without the symptom of post nasal drip

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center, Vanderbilt Digestive Disease Clinic, TVC, Room 1660	Nashville	Tennessee	United States	37232-5280

Sponsors and Collaborators

• Vanderbilt University
• TAP Pharmaceutical Products Inc.

Investigators

• Principal Investigator: Michael F Vaezi, MD PhD MS, Vanderbilt University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael Vaezi, Medical Director, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT00335283
• Other Study ID Numbers: 051169
• First Posted: Jun 9, 2006
• Last Update Posted: Aug 21, 2012
• Last Verified: Jun 1, 2012

• Additional relevant MeSH terms: Laryngeal Diseases; Lansoprazole; Dexlansoprazole

Study Results

Participant Flow

Recruitment Details	The PI and/or study coordinator or other GI research nurses will meet with the patients referred by Vanderbilt's Asthma, Sinus and Allergy Program. The patients will be given the consent form to read, the document will be reviewed, and all questions will be answered.

Arm/Group Title	Lansoprazole	Placebo (Sugar Pill)
Arm/Group Description	40 mg twice a day	one tablet twice a day
Period Title: Overall Study
STARTED	36	39
COMPLETED	30	34
NOT COMPLETED	6	5

Baseline Characteristics

Arm/Group Title	Lansoprazole	Placebo (Sugar Pill)	Total
Arm/Group Description	40 mg twice a day	one tablet twice a day	Total of all reporting groups
Overall Participants	36	39	75
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	33 91.7%	36 92.3%	69 92%
>=65 years	3 8.3%	3 7.7%	6 8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46 (15)	45 (13)	45 (14)
Sex: Female, Male (Count of Participants)
Female	30 83.3%	26 66.7%	56 74.7%
Male	6 16.7%	13 33.3%	19 25.3%
Region of Enrollment (participants) [Number]
United States	36 100%	39 100%	75 100%

Outcome Measures

1. Primary Outcome

Title	Post Nasal Drainage Symptom Response
Description	The primary outcome measure was postnasal drainage symptom response measured by using a visual analogue scale. At 8 and 16 weeks, a horizontal symptoms scale from 0% (no change) to 100% (symptoms completely resolved) was presented to participants to assess improvement in postnasal drainage symptoms.
Time Frame	8 and 16 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed per the protocol. At the completion of the study, all data were analyzed by the department of statistics and epidemiologyfor the primary outcome of interest, which was response rate for both lansoprazole and placebo. Univariate and multivariate analyses was performed on the collected data.

Arm/Group Title	Lansoprazole	Placebo (Sugar Pill)
Arm/Group Description	40 mg twice a day	one tablet twice a day
Measure Participants	30	34
8 week	55	3.5
16 week	50	5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lansoprazole, Placebo (Sugar Pill)
	Comments	This applies to the 8 week treatment effect. A sample size of 33 patients in treated arm was considered sufficient to detect a difference of 35% between groups, assuming a lansoprazole treatment response of 70% and a placebo response of 35% with an alpha level of .05 and 90% power. A total of 75 patienst was considered an adequate sample size to allow for a 10% dropout rate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.01
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	3.12
	Confidence Interval	(2-Sided) 95%; 1.28 to 7.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lansoprazole, Placebo (Sugar Pill)
	Comments	This applies to the 16 week treatment affect. A sample size of 33 patients in treated arm was considered sufficient to detect a difference of 35% between groups, assuming a lansoprazole treatment response of 70% and a placebo response of 35% with an alpha level of .05 and 90% power. A total of 75 patienst was considered an adequate sample size to allow for a 10% dropout rate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.006
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 95%; 1.41 to 8.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Rhinosinusitis Outcome Measure(RSOM-31)
Description	RSOM-31 includes 31 questions combined into a total score ranging from 0 to 155 with higher scores representing greater disease burden. Values are based on patient report.
Time Frame	Baseline, 8 weeks, and 16 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed per the protocol. At the completion of the study, all data were analyzed by the department of statistics and epidemiologyfor the primary outcome of interest, which was response rate for both lansoprazole and placebo. Univariate and multivariate analyses was performed on the collected data.

Arm/Group Title	Lansoprazole	Placebo (Sugar Pill)
Arm/Group Description	40 mg twice a day	one tablet twice a day
Measure Participants	30	34
Baseline	63	51
8 weeks	40	36
16 weeks	35	35

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lansoprazole, Placebo (Sugar Pill)
	Comments	This applies to the 8 week treatment effect. A sample size of 33 patients in treated arm was considered sufficient to detect a difference of 35% between groups, assuming a lansoprazole treatment response of 70% and a placebo response of 35% with an alpha level of .05 and 90% power. A total of 75 patienst was considered an adequate sample size to allow for a 10% dropout rate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.97
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.38 to 2.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lansoprazole, Placebo (Sugar Pill)
	Comments	This applies to the 16 week treatment effect. A sample size of 33 patients in treated arm was considered sufficient to detect a difference of 35% between groups, assuming a lansoprazole treatment response of 70% and a placebo response of 35% with an alpha level of .05 and 90% power. A total of 75 patienst was considered an adequate sample size to allow for a 10% dropout rate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.84
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.40 to 3.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Sino Nasal Outcome Test (SNOT-20)
Description	SNOT-20 includes 20 questions combined into a total score ranging from 0 to 100 with higher numbers representing greater rhinosinusitis health burden and represents patient-reported symptom severity.
Time Frame	Baseline, 8 weeks and 16 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed per the protocol. At the completion of the study, all data were analyzed by the department of statistics and epidemiologyfor the primary outcome of interest, which was response rate for both lansoprazole and placebo. Univariate and multivariate analyses was performed on the collected data.

Arm/Group Title	Lansoprazole	Placebo (Sugar Pill)
Arm/Group Description	40 mg twice a day	one tablet twice a day
Measure Participants	30	34
Baseline	36	35
8 weeks	25	32
16 weeks	20	27

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lansoprazole, Placebo (Sugar Pill)
	Comments	This applies to the 8 week treatment effect. A sample size of 33 patients in treated arm was considered sufficient to detect a difference of 35% between groups, assuming a lansoprazole treatment response of 70% and a placebo response of 35% with an alpha level of .05 and 90% power. A total of 75 patienst was considered an adequate sample size to allow for a 10% dropout rate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.06
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	2.44
	Confidence Interval	(2-Sided) 95%; .95 to 6.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lansoprazole, Placebo (Sugar Pill)
	Comments	This applies to the 16 week treatment effect. A sample size of 33 patients in treated arm was considered sufficient to detect a difference of 35% between groups, assuming a lansoprazole treatment response of 70% and a placebo response of 35% with an alpha level of .05 and 90% power. A total of 75 patienst was considered an adequate sample size to allow for a 10% dropout rate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.007
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	4.51
	Confidence Interval	(2-Sided) 95%; 1.5 to 13.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Quality of Life Questionnaire (QOLRAD)
Description	The patient-reported QOLRAD consists of 25 questions combined into a total score ranging from 25 to 175 with higher numbers representing better quality of life.
Time Frame	Baseline, 8 weeks and 16 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed per the protocol. At the completion of the study, all data were analyzed by the department of statistics and epidemiologyfor the primary outcome of interest, which was response rate for both lansoprazole and placebo. Univariate and multivariate analyses was performed on the collected data.

Arm/Group Title	Lansoprazole	Placebo (Sugar Pill)
Arm/Group Description	40 mg twice a day	one tablet twice a day
Measure Participants	30	34
Baseline	155	160
8 weeks	174	155
16 weeks	173	160

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lansoprazole, Placebo (Sugar Pill)
	Comments	This applies to the 8 week treatment effect. A sample size of 33 patients in treated arm was considered sufficient to detect a difference of 35% between groups, assuming a lansoprazole treatment response of 70% and a placebo response of 35% with an alpha level of .05 and 90% power. A total of 75 patienst was considered an adequate sample size to allow for a 10% dropout rate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.006
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	5.17
	Confidence Interval	(2-Sided) 95%; 2.02 to 13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lansoprazole, Placebo (Sugar Pill)
	Comments	This applies to the 16 week treatment effect. A sample size of 33 patients in treated arm was considered sufficient to detect a difference of 35% between groups, assuming a lansoprazole treatment response of 70% and a placebo response of 35% with an alpha level of .05 and 90% power. A total of 75 patienst was considered an adequate sample size to allow for a 10% dropout rate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	5.31
	Confidence Interval	(2-Sided) 95%; 1.97 to 14.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Lansoprazole		Placebo (Sugar Pill)
Arm/Group Description	40 mg twice a day		one tablet twice a day
All Cause Mortality
	Lansoprazole		Placebo (Sugar Pill)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lansoprazole		Placebo (Sugar Pill)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	Lansoprazole		Placebo (Sugar Pill)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/39 (0%)

Limitations/Caveats

Sample size of 75 participants is small. Lack of an objective measure of postnasal drainage limited the study outcome to be symptom based.

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.