Sham CPAP vs. Straight CPAP for Chronic Cough

Prospective Study of Efficacy of Sham CPAP vs. Straight CPAP on Cough Intensity in Patients With Chronic Cough

Chronic cough is an important clinical problem in primary care and sub-specialty practice. Besides the distress experienced by patients with chronic cough, significant healthcare resources are expended to understand the role of gastroesophageal reflux, asthma and post-nasal drip in understanding their contribution to cough.

Obstructive sleep apnea (OSA) is common in patients with chronic cough. More importantly, treatment of OSA with continuous positive airway pressure (CPAP) has led to improvement in cough for chronic cough patients. Mechanisms by which OSA therapy with CPAP can improve cough includes beneficial effects on reflux and airway inflammation.

The aim of this study is to definitively establish that CPAP therapy for treatment of OSA in chronic cough patients improves cough. While these patients with chronic cough are not routinely screened and treated for OSA, this study aims to evaluate these chronic cough patients with screening questionnaires for OSA and if necessary with polysomnography and randomize them to either CPAP or sham CPAP for 6 weeks.

Study Overview

• Status: Completed
• Conditions: OSA; Chronic Cough
• Intervention / Treatment: Device: Straight CPAP; Device: Sham CPAP

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cough of more than 2 month duration
• Not active smoker with history of stoppage of smoking for more than 6 months
• Evaluation and treatment by other providers for suspected gastroesophageal reflux disease (GERD), upper airway cough syndrome (UACS), or cough-variant asthma (CVA) for at least 1 month
• Normal chest radiography or computed tomography (CT) scans (patients with up to 2 lung nodules less than 3 mm will be allowed if there is no history of malignancy elsewhere)
• Normal spirometry with predicted diffusing capacity of the lung for carbon dioxide (DLCO) more than 50% predicted. Pulmonary Function Test criteria: no evidence of airflow limitation (FEV1/FVC > 0.7) or significant chest restriction (FVC > 70% predicted) with predicted DLCO more than 50% predicted

Exclusion Criteria:

• Pregnancy
• Recent pneumonia (less than 6 months)
• Congestive heart failure, acute or chronic renal disease, jaundice or chronic liver disease, pulmonary embolism, stroke or neurodegenerative disease, malignancy
• Use of supplemental oxygen or positive airway pressure therapy (if patients have been diagnosed with obstructive sleep apnea in the past but were non-compliant with positive airway pressure therapy, they will not be excluded)
• Use of opiates for cough suppression (opiate use for pain suppression can be included)
• Alcoholism, drug dependence (including chewing tobacco) or illicit drug use
• Esophageal cancer or laryngeal surgery
• Craniofacial abnormalities that preclude CPAP placement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Straight CPAP; Patients randomized to straight CPAP will receive 10 cm of air pressure, or as determined by the results of polysomnography, for 6 weeks. Following the 6-week visit, patients will be placed on straight CPAP with equipment approved by insurance for an additional 6 weeks.	Device: Straight CPAP
SHAM_COMPARATOR: Sham CPAP; Patients randomized to sham CPAP will receive 1-2 cm of air pressure for 6 weeks. Following the 6-week visit, patients will be placed on straight CPAP with equipment approved by insurance for an additional 6 weeks.	Device: Sham CPAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Leicester Cough Questionnaire Score	Subjects will complete the Leicester Cough Questionnaire at the baseline and 6-week visits. The Leicester Cough Questionnaire comprises 19 items, which assess symptoms, or the impact of symptoms, over the last 2 weeks on a seven-point Likert scale. Scores in three domains (physical, psychological and social) are calculated as a mean for each domain (range 1 to 7). A total score (range 3 to 21) is also calculated by adding the domain scores together. Higher scores indicate better quality of life. The change in Leicester Cough Questionnaire score will be compared between the Straight CPAP and Sham CPAP groups	Baseline and 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cough Frequency	Subjects will wear a Leicester cough monitor for 24 hours at the baseline and 6-week visits, which will record cough frequency during that period. The change in cough frequency from baseline to 6 weeks will be compared between the Straight CPAP and SHAM CPAP groups	Baseline and 6 weeks
8 Isoprostane Level in Exhaled Breath Condensate	Samples of breath condensate will be collected from study subjects at the baseline and 6-week visits. The 8 isoprostane level from baseline to 6-weeks will be compared between the Straight CPAP and Sham CPAP groups	Baseline and 6 weeks
Interleukin-8 (IL-8) Level in Exhaled Breath Condensate	Samples of breath condensate will be collected from study subjects at the baseline and 6-week visits. IL-6 level from baseline to 6-weeks will be compared between the Straight CPAP and Sham CPAP groups	Baseline and 6 weeks
Nitrite/Nitrate (NOX) Level in Exhaled Breath Condensate	Samples of breath condensate will be collected from study subjects at the baseline and 6-week visits. NOX level from baseline to 6-weeks will be compared between the Straight CPAP and Sham CPAP groups.	Baseline and 6 weeks
Hydrogen Peroxide (H2O2) Level in Exhaled Breath Condensate	Samples of breath condensate will be collected from study subjects at the baseline and 6-week visits. H2O2 level from baseline to 6-weeks will be compared between the Straight CPAP and Sham CPAP groups	Baseline and 6 weeks
Change in Leukotriene B4 (LTB4) Level in Exhaled Breath Condensate	Samples of breath condensate will be collected from study subjects at the baseline and 6-week visits. The change in LTB4 level from baseline to 6-weeks will be compared between the Straight CPAP and Sham CPAP groups	Baseline and 6 weeks
Change in Gastroesophageal Reflux Disease Quality of Life (GERD-QoL) Questionnaire Score	Subjects will complete the GERD-QoL questionnaire at the baseline and 6-week visits. The GERD-QoL comprises 15 items on a five-point Likert scale; lowest possible score (0) = no symptoms, greatest possible score (75) = worst symptoms. The change in GERD-QoL score will be compared between the Straight CPAP and Sham CPAP groups	Baseline and 6 weeks

Collaborators and Investigators

• Sponsor: Krishna M. Sundar
• Investigators: Principal Investigator: Krishna Sundar, MD, University of Utah

Publications and helpful links

General Publications

• Sundar KM, Willis AM, Smith S, Hu N, Kitt JP, Birring SS. A Randomized, Controlled, Pilot Study of CPAP for Patients with Chronic Cough and Obstructive Sleep Apnea. Lung. 2020 Jun;198(3):449-457. doi: 10.1007/s00408-020-00354-1. Epub 2020 Apr 30.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 13, 2014
• Primary Completion (ACTUAL): November 25, 2019
• Study Completion (ACTUAL): November 25, 2019

Study Registration Dates

• First Submitted: May 27, 2017
• First Submitted That Met QC Criteria: May 27, 2017
• First Posted (ACTUAL): June 1, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 18, 2020
• Last Update Submitted That Met QC Criteria: June 4, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Obstructive Sleep Apnea; CPAP
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Cough
• Other Study ID Numbers: IRB #62049

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes