Cough, GERD
Conditions
Keywords
Cough, GERD
Brief summary
The purpose of this research study is to investigate different doses of proton pump inhibitors in reducing cough symptoms felt to be associated with Gastroesophageal reflux disease (GERD). Proton pump inhibitors are medicines used to treat GERD, which work by lowering the amount of acid in the stomach. The proton pump inhibitor used in this study is called, Esomeprazole (brand name Nexium), and is already marketed for treating GERD. Patients with GERD may experience all or some of the following symptoms: stomach acid or partially digested food re-entering the esophagus (which is sometimes referred to as heartburn or regurgitation), belching and coughing. Even very small, unnoticeable amounts of rising stomach acid may cause patients to cough. Because there may be a link between chronic cough and GERD, study doctors are interested in learning if giving high-dose Nexium (40 milligrams, twice daily) will help in treating chronic cough.
Detailed description
This study will be a randomized, double-blind, placebo controlled, comparative parallel-group trial of subjects with chronic cough of unknown origin presenting to the Otolaryngology/ Head and Neck Surgery, Pulmonary Medicine, and Gastroenterology outpatient clinics at the University of North Carolina Hospital system. Potential subjects with chronic cough of unknown origin will be identified through the above outpatient clinics. Those who meet the inclusion and exclusion criteria will be asked to join the study testing the efficacy of twice daily esomeprazole 40 mg taken for 3 months in the setting of chronic cough. Potential subjects will be consented for the study prior to leaving the enrolling clinic. A total of 40 subjects will be recruited into our study.
Interventions
DRUGEsomeprazole
40mg capsule BID for 12 weeks
DRUGPlacebo
placebo capsule BID for 12 weeks
Sponsors
AstraZeneca
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. males and females (of non-childbearing potential. ie-surgically sterile, or willing to use an approved form of birth control) between the ages of 18 and 70 who speak and write in English, 2. chronic cough (\> 8 wks/another article used \> 6 wks) with symptom severity criteria of 2 or greater on the Fisman Cough Severity Score and 3 or greater or the Fisman Cough Frequency Score, and, 3. failure to respond to post nasal drip therapy.
Exclusion criteria
1. abnormal chest x-ray, 2. patients taking H2 blockers within the previous 3 days or PPI's within the previous 7 days, 3. failure to respond to past PPI therapy given for cough that lasted at least 12 weeks, 4. use of an investigational drug within the past 30 days, 5. previous surgical antireflux or non-surgical endoscopic anti-reflux procedure (ex., Stretta or endoscopic sewing device), 6. previous aerodigestive malignancy, 7. current smokers, or ex-smokers (defined as those who quit smoking less than 3 months prior to study enrollment or those who have quit, but have a 20 pack year smoking history), 8. upper respiratory infection within 8 weeks prior to study enrollment, 9. current use of a B- blocker, ACE-I, or anticholinesterases at time of enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cough-Specific Quality of Life Questionnaire | baseline and 12 weeks | It is a validated, 28-item assessment tool designed to evaluate decrements in quality of life due to chronic cough. This questionnaire measures cough-related symptoms, as well as the social implications and psychological impact. Examples of items include, I cannot sleep at night and I cough and it makes me retch. The final score is obtained by summing the responses to 28 questions, each scored on a 1-4 scale, where 1 is strongly disagree, and 4 is strongly agree. The minimum and maximum CQLQ scores are 28 and 112 respectively, with increasing score indicating more severe impairment. |
Countries
United States
Participant flow
Recruitment details
recruited from hospital clinics - subjects with chronic cough.
Pre-assignment details
. After initial eligibility screening, all consenting participants entered a 7-day run-in period, during which all subjects took a placebo pill twice a day, for the purpose of ensuring compliance with study medication and assessment of cough severity under baseline conditions.
Participants by arm
| Arm | Count |
|---|---|
| Esomeprazole Arm Upon successful completion of the run-in period, participants in the esomeprazole arm were given the compound at a dose of 40mg for 12 weeks. All participants were instructed to take their study medication 30 minutes before breakfast and 30 minutes before dinner. Esomeprazole was supplied by the investigational pharmacy at the University of North Carolina as blue capsules without identifying features. | 22 |
| Placebo Upon successful completion of the run-in period, participants randomized to receive to the placebo arm got a capsule identical to the esomeprazole arm, but containing an inert substance, twice daily for 12 weeks. All participants were instructed to take their study medication 30 minutes before breakfast and 30 minutes before dinner. | 18 |
| Total | 40 |
Baseline characteristics
| Characteristic | Placebo | Esomeprazole Arm | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 20 Participants | 37 Participants |
| Age Continuous | 51.0 years STANDARD_DEVIATION 11.6 | 49.5 years STANDARD_DEVIATION 12 | 50 years STANDARD_DEVIATION 11.7 |
| Region of Enrollment United States | 18 participants | 22 participants | 40 participants |
| Sex: Female, Male Female | 15 Participants | 16 Participants | 31 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 22 | 0 / 18 |
| serious Total, serious adverse events | 0 / 22 | 0 / 18 |
Outcome results
Primary
Change in Cough-Specific Quality of Life Questionnaire
It is a validated, 28-item assessment tool designed to evaluate decrements in quality of life due to chronic cough. This questionnaire measures cough-related symptoms, as well as the social implications and psychological impact. Examples of items include, I cannot sleep at night and I cough and it makes me retch. The final score is obtained by summing the responses to 28 questions, each scored on a 1-4 scale, where 1 is strongly disagree, and 4 is strongly agree. The minimum and maximum CQLQ scores are 28 and 112 respectively, with increasing score indicating more severe impairment.
Time frame: baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Esomeprazole Arm | Change in Cough-Specific Quality of Life Questionnaire | 9.8 participants | Standard Deviation 12.2 |
| Placebo | Change in Cough-Specific Quality of Life Questionnaire | 5.8 participants | Standard Deviation 11.1 |