Larynx Disease
Conditions
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.
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.
Interventions
DRUGLansoprazole Tablet
40 mg bid x 16 weeks
PROCEDUREPH and impedence testing
24 hour ph monitoring
PROCEDUREmanometry
done prior to pH probe to measure length of esophagus
DRUGlansoprazole
40mg bid
DRUGplacebo
one tablet bid
Sponsors
TAP Pharmaceutical Products Inc.
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Lansoprazole 40 mg twice a day | 36 |
| Placebo (Sugar Pill) one tablet twice a day | 39 |
| Total | 75 |
Baseline characteristics
| Characteristic | Placebo (Sugar Pill) | Lansoprazole | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 33 Participants | 69 Participants |
| Age Continuous | 45 years STANDARD_DEVIATION 13 | 46 years STANDARD_DEVIATION 15 | 45 years STANDARD_DEVIATION 14 |
| Region of Enrollment United States | 39 participants | 36 participants | 75 participants |
| Sex: Female, Male Female | 26 Participants | 30 Participants | 56 Participants |
| Sex: Female, Male Male | 13 Participants | 6 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 36 | 0 / 39 |
| serious Total, serious adverse events | 0 / 36 | 0 / 39 |
Outcome results
Primary
Post Nasal Drainage Symptom Response
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lansoprazole | Post Nasal Drainage Symptom Response | 8 week | 55 Scores on a Scale |
| Lansoprazole | Post Nasal Drainage Symptom Response | 16 week | 50 Scores on a Scale |
| Placebo (Sugar Pill) | Post Nasal Drainage Symptom Response | 16 week | 5 Scores on a Scale |
| Placebo (Sugar Pill) | Post Nasal Drainage Symptom Response | 8 week | 3.5 Scores on a Scale |
Comparison: 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.p-value: 0.0195% CI: [1.28, 7.59]Regression, Logistic
Comparison: 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.p-value: 0.00695% CI: [1.41, 8.67]Regression, Logistic
Secondary
Quality of Life Questionnaire (QOLRAD)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lansoprazole | Quality of Life Questionnaire (QOLRAD) | Baseline | 155 Scores on a Scale |
| Lansoprazole | Quality of Life Questionnaire (QOLRAD) | 8 weeks | 174 Scores on a Scale |
| Lansoprazole | Quality of Life Questionnaire (QOLRAD) | 16 weeks | 173 Scores on a Scale |
| Placebo (Sugar Pill) | Quality of Life Questionnaire (QOLRAD) | 8 weeks | 155 Scores on a Scale |
| Placebo (Sugar Pill) | Quality of Life Questionnaire (QOLRAD) | Baseline | 160 Scores on a Scale |
| Placebo (Sugar Pill) | Quality of Life Questionnaire (QOLRAD) | 16 weeks | 160 Scores on a Scale |
Comparison: 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.p-value: 0.00695% CI: [2.02, 13.2]Regression, Logistic
Comparison: 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.p-value: 0.00195% CI: [1.97, 14.3]Regression, Logistic
Secondary
Rhinosinusitis Outcome Measure(RSOM-31)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lansoprazole | Rhinosinusitis Outcome Measure(RSOM-31) | Baseline | 63 Scores on a Scale |
| Lansoprazole | Rhinosinusitis Outcome Measure(RSOM-31) | 8 weeks | 40 Scores on a Scale |
| Lansoprazole | Rhinosinusitis Outcome Measure(RSOM-31) | 16 weeks | 35 Scores on a Scale |
| Placebo (Sugar Pill) | Rhinosinusitis Outcome Measure(RSOM-31) | Baseline | 51 Scores on a Scale |
| Placebo (Sugar Pill) | Rhinosinusitis Outcome Measure(RSOM-31) | 8 weeks | 36 Scores on a Scale |
| Placebo (Sugar Pill) | Rhinosinusitis Outcome Measure(RSOM-31) | 16 weeks | 35 Scores on a Scale |
Comparison: 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.p-value: 0.9795% CI: [0.38, 2.7]Regression, Logistic
Comparison: 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.p-value: 0.8495% CI: [0.4, 3.06]Regression, Logistic
Secondary
Sino Nasal Outcome Test (SNOT-20)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Lansoprazole | Sino Nasal Outcome Test (SNOT-20) | Baseline | 36 Scores on a Scale |
| Lansoprazole | Sino Nasal Outcome Test (SNOT-20) | 8 weeks | 25 Scores on a Scale |
| Lansoprazole | Sino Nasal Outcome Test (SNOT-20) | 16 weeks | 20 Scores on a Scale |
| Placebo (Sugar Pill) | Sino Nasal Outcome Test (SNOT-20) | Baseline | 35 Scores on a Scale |
| Placebo (Sugar Pill) | Sino Nasal Outcome Test (SNOT-20) | 8 weeks | 32 Scores on a Scale |
| Placebo (Sugar Pill) | Sino Nasal Outcome Test (SNOT-20) | 16 weeks | 27 Scores on a Scale |
Comparison: 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.p-value: 0.0695% CI: [0.95, 6.31]Regression, Logistic
Comparison: 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.p-value: 0.00795% CI: [1.5, 13.6]Regression, Logistic