The Utility of Nexium in Chronic Cough and Reflux Disease

Chronic Cough and Reflux Disease: A Randomized, Double-Blinded, Placebo Controlled Trial of High Dose Proton Pump Inhibition

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.

Study Overview

• Status: Completed
• Conditions: Cough; GERD
• Intervention / Treatment: Drug: Esomeprazole; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Gastroenterology, UNC Pulmonology, UNC ENT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 40mg Esomeprazole BID	Drug: Esomeprazole; 40mg capsule BID for 12 weeks; Other Names: Brand name is Nexium
Placebo Comparator: 2; placebo capsules	Drug: Placebo; placebo capsule BID for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline and 12 weeks

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Nicholas Shaheen, MD, MPH, UNC Gastroenterology

Publications and helpful links

General Publications

• Shaheen NJ, Crockett SD, Bright SD, Madanick RD, Buckmire R, Couch M, Dellon ES, Galanko JA, Sharpless G, Morgan DR, Spacek MB, Heidt-Davis P, Henke D. Randomised clinical trial: high-dose acid suppression for chronic cough - a double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2011 Jan;33(2):225-34. doi: 10.1111/j.1365-2036.2010.04511.x. Epub 2010 Nov 17.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: February 3, 2006
• First Submitted That Met QC Criteria: February 3, 2006
• First Posted (Estimate): February 6, 2006

Study Record Updates

• Last Update Posted (Estimate): January 10, 2012
• Last Update Submitted That Met QC Criteria: January 6, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: GERD; Cough
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole
• Other Study ID Numbers: AZ COUGH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No