Prospective Study on the Evaluation, Patient Reported Outcomes and Effectiveness of Treatment for Chronic Cough

Chronic Cough Clinical Trial

— PROCOUGH  

Official title:

Prospective Study on the Evaluation, Patient Reported Outcomes and Effectiveness of Treatment for Chronic Cough in Secondary Care

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04758351
• Other study ID #: 59689
• Status: Recruiting
• Start date: December 14, 2021
• Est. completion date: April 30, 2024

Study information

• Verified date: March 2023
• Source: McMaster University
• Contact: Imran Satia, MD, PhD
• Phone: 905-521-2100
• Email: satiai[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Chronic cough is a common troublesome symptom which has a global prevalence of approximately 10%, but with wide variations across continents. The aim of this study is to evaluate the effectiveness of treatment, patient-reported outcomes and burden of disease in patients with chronic cough referred to a specialist clinic. The proposed study will use pre-defined diagnostic criteria, investigations and treatment algorithms such that all recruited patients will undergo the same investigations and follow a set management algorithm. This study will objectively and subjectively assess coughing at baseline and after treatment in a real-world clinical setting. This will allow us to understand the relationship between any objective reduction in cough after treatment, and whether this translates to any significant improvement in subjective questionnaire scores. We will assess the impact of health conditions on lost productivity in monetary units and assess the amount of absenteeism, presenteeism and daily activity impairment attributable to unexplained chronic cough/refractory chronic cough. Finally, a patient survey at the end of the study will evaluate the patients' satisfaction and experience of investigation, management trials and use of questionnaires.

Description:

This is a prospective observational single-center study of patients referred to secondary care for investigation and management of explained chronic cough, refractory chronic cough, and unexplained chronic cough. The study will have 4 research visits integrated between standard clinical visits. Patients will be recruited from secondary care clinics. Patient eligibility will be assessed against the study inclusion/exclusion criteria and patients will undergo informed consent in the research centre. Subjects who provide informed consent and are enrolled in the study will undergo screening procedures.

At Visit 1 (screening) data on demographics and medical history will be collected and a complete physical examination will be conducted. Subjects will undergo skin prick testing and spirometry and complete self-reported questionnaires (Leicester Cough Questionnaire, Valuation of Lost Productivity, Work Productivity, Activity, and Impairment, Healthcare Resource Utilization, Reflux Disease Questionnaire, Sino-Nasal Outcome Test, and Global Rating of Change Scale). Subjects will be fitted with a 24-hour cough monitor.

At Visit 2, the 24-hour cough monitor will be removed. Subjects will undergo blood sampling, methacholine challenge, sputum induction, and provide a urine sample.

Between Visits 2 and 3, physicians will provide a single clinical treatment pathway to address the most likely cause of chronic cough. Treatment for chronic cough will be in line with current clinical practice guidelines published by the European Respiratory Society Taskforce on Chronic Cough. Treatment plans will range from 2 weeks to 3 months.

Visit 3 will occur 2 weeks to 3 months following subjects' second clinical visit. Subjects will complete self-reported questionnaires (Leicester Cough Questionnaire, Valuation of Lost Productivity, Work Productivity, Activity, and Impairment, Reflux Disease Questionnaire, Sino-Nasal Outcome Test, and Global Rating of Change Scale) and be fitted with a 24-hour cough monitor.

At Visit 4 the 24-hour cough monitor will be removed. Subjects will undergo blood sampling, sputum induction, and provide a urine sample. Subjects will complete a patient satisfaction survey.

All study procedures will be performed according to local standard operating procedures and be conducted by trained and experienced staff with supervision by medical doctors. Safety will be assessed throughout the study by monitoring for adverse events and serious adverse events.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: April 30, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Aged =18-75

2. Patients referred to a specialist primarily with a history of chronic cough (cough lasting >8 weeks)

3. Normal Chest X-ray

4. No Evidence of Airflow Obstruction

Exclusion Criteria:

1. Subjects who are currently established on treatment and their chronic cough is well controlled.

2. Unable to perform acceptable and reproducible spirometry.

3. Current smoker or ex-smoker with =20 pack-year smoking history and abstinence of =6 months

4. Symptoms of upper respiratory tract infection in the last 1 month which have not resolved

5. Lower respiratory tract infection or pneumonia in the last 1 month

6. Asthma exacerbation in the previous month requiring an increase or start of an inhaled corticosteroid or oral corticosteroid

7. Significant other primary pulmonary disorders in particular; pulmonary embolism, pulmonary hypertension, lung cancer, cystic fibrosis, significant radiologically proven emphysema, interstitial lung disease or bronchiectasis.

8. Any centrally acting medication within the last 2 weeks which in the view of the investigator could influence the coughing. Any participant who is taking amitriptyline, dextromethorphan, pregabalin, gabapentin or opioids will not be eligible to take part in this study unless they are willing and medically able to withdraw from such medication before the start of visit 1. The reason for this is that centrally-acting medications may influence coughing rates at baseline.

9. History of psychiatric illness, drug or alcohol abuse which may interfere in the participation of the trial.

10. Positive Covid-19 test within 2 weeks of screening visit.

Related Conditions & MeSH terms

• Chronic Cough
• Cough

Intervention

Other:
• Usual clinical practice
Based on European Respiratory Society guidelines on management for chronic cough.

Locations

Country	Name	City	State
Canada	Imran Satia	Hamilton	Ontario

Sponsors (4)

Lead Sponsor	Collaborator
McMaster University	Merck Canada Inc., University of British Columbia, University of Manchester

Country where clinical trial is conducted

Canada, 

References & Publications (6)

Andreasson E, Svensson K, Berggren F. PRP11 The validity of the work productivity and activity impairment questionnaire for patients with asthma (WPAIASTHMA): Results from a web-based study. Value in Health. 2003;6(6):780.

Irwin RS, Baumann MH, Bolser DC, Boulet LP, Braman SS, Brightling CE, Brown KK, Canning BJ, Chang AB, Dicpinigaitis PV, Eccles R, Glomb WB, Goldstein LB, Graham LM, Hargreave FE, Kvale PA, Lewis SZ, McCool FD, McCrory DC, Prakash UBS, Pratter MR, Rosen MJ, Schulman E, Shannon JJ, Hammond CS, Tarlo SM. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan;129(1 Suppl):1S-23S. doi: 10.1378/chest.129.1_suppl.1S. No abstract available. — View Citation

Morice AH, Kastelik JA. Cough. 1: Chronic cough in adults. Thorax. 2003 Oct;58(10):901-7. doi: 10.1136/thorax.58.10.901. — View Citation

Pratter MR. Overview of common causes of chronic cough: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan;129(1 Suppl):59S-62S. doi: 10.1378/chest.129.1_suppl.59S. — View Citation

Sadatsafavi M, Rousseau R, Chen W, Zhang W, Lynd L, FitzGerald JM. The preventable burden of productivity loss due to suboptimal asthma control: a population-based study. Chest. 2014 Apr;145(4):787-793. doi: 10.1378/chest.13-1619. — View Citation

Song WJ, Chang YS, Faruqi S, Kim JY, Kang MG, Kim S, Jo EJ, Kim MH, Plevkova J, Park HW, Cho SH, Morice AH. The global epidemiology of chronic cough in adults: a systematic review and meta-analysis. Eur Respir J. 2015 May;45(5):1479-81. doi: 10.1183/09031936.00218714. Epub 2015 Feb 5. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlation in exhaled nitric oxide, blood eosinophils, and sputum eosinophils and objective cough frequency and subjective patient reported outcomes	Correlations between exhaled nitric oxide, blood eosinophils, and sputum eosinophils and objective cough frequency and subjective patient reported outcomes pre- and post-treatment in patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, unexplained chronic cough.	3 months
Other	Changes in the quality of life	Changes in the quality of life, measured using the Leicester Cough Questionnaire pre- and post-treatment in patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, unexplained chronic cough.The Leicester Cough Questionnaire is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.	3 months
Other	Changes in the perceived disease	Changes in perceived disease improvement, measured using the Global Rating of Change Scale, pre- and post-treatment in patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, unexplained chronic cough. The Global Rating of Change Scale is a 15 point scale with a minimum value of -7 indicating a worse outcome and a maximum value of +7 indicating a better outcome.	3 months
Other	Correlations between improved quality of life and perceived disease improvement	Correlations between improved quality of life, measured using the Leicester Cough Questionnaire, and perceived disease improvement, measure using the Global Rating of Change Scale, pre- and post-treatment in patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, unexplained chronic cough.	3 months
Primary	Changes in objective cough frequency	Change in objective cough frequency pre- and post-treatment among patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough.	3 months
Secondary	Correlation in change of objective cough frequency and healthcare utilization	Correlation between pre- and post-treatment change in objective cough frequency and Healthcare Related Utilization among patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough. Healthcare utilization is measured by recording the number of visits to family physician, outpatient specialist, number of tests, and medication use.	3 months
Secondary	Correlation in change of objective cough frequency and lost productivity	Correlation between pre- and post-treatment change in objective cough frequency and lost productivity among patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough. Lost productivity is measured using the Valuation of Lost Productivity questionnaire which contains a series of questions that evaluate the impact of functional impairment on productivity loss, not just for the individual but also on the work environment.	3 months
Secondary	Correlation in change of objective cough frequency and work productivity and activity	Correlation between pre- and post-treatment change in objective cough frequency and work productivity and activity among patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough. Work productivity and activity is measured using the Work Productivity and Activity Impairment Questionnaire which is a 6-item self-administered questionnaire used to assess productivity and impairment because of a specific health problem such as chronic cough.	3 months
Secondary	Correlation in change of quality of life and healthcare utilization	Correlation between pre- and post-treatment change in quality of life and Healthcare Related Utilization among patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough. Quality of life is measured using the Leicester Cough Questionnaire. The Leicester Cough Questionnaire is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time. Healthcare utilization is measured by recording the number of visits to family physician, outpatient specialist, number of tests, and medication use.	3 months
Secondary	Correlation in change of quality of life and lost productivity	Correlation between pre- and post-treatment change in quality of life and lost productivity among patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough. Quality of life is measured using the Leicester Cough Questionnaire. The Leicester Cough Questionnaire is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time. Lost productivity is measured using the Valuation of Lost Productivity questionnaire which contains a series of questions that evaluate the impact of functional impairment on productivity loss, not just for the individual but also on the work environment.	3 months
Secondary	Correlation in change of quality of life and work productivity and activity	Correlation between pre- and post-treatment change in quality of life and work productivity and activity among patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough. Quality of life is measured using the Leicester Cough Questionnaire. The Leicester Cough Questionnaire is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time. Work productivity and activity is measured using the Work Productivity and Activity Impairment Questionnaire which is a 6-item self-administered questionnaire used to assess productivity and impairment because of a specific health problem such as chronic cough.	3 months
Secondary	Patient satisfaction	Patient satisfaction measurements of clinical investigations, treatment, and use of questionnaires among patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough. Patient satisfaction will be measured using a 5 point Likert scale where the minimum value is 1 indicating participants were very unsatisfied and the maximum value is 5 indicating participants were very satisfied.	3 months
Secondary	Comparison of change in objective cough frequency and quality of life	Comparison of pre- and post treatment change in objective cough frequency and quality of life among patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough. Quality of life is measured using the Leicester Cough Questionnaire. The Leicester Cough Questionnaire is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.	3 months
Secondary	Comparison of change in objective cough frequency and participant perceived change in condition	Comparison of pre- and post-treatment change in objective cough frequency and perceived change in condition among patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough. Perceived change in condition is measured using the Global Rating of Change Scale which is a 15 value scale. The Global Rating of Change Scale is a 15 point scale with a minimum value of -7 indicating a worse outcome and a maximum value of +7 indicating a better outcome.	3 months
Secondary	Measure the relationship between objective cough frequency and lost productivity	Measure the post treatment relationship between objective cough frequency and lost productivity among patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough. Lost productivity is measured using the Valuation of Lost Productivity questionnaire which contains a series of questions that evaluate the impact of functional impairment on productivity loss, not just for the individual but also on the work environment.	3 months
Secondary	Measure the relationship between objective cough frequency and work productivity and activity	Measure the post treatment relationship between objective cough frequency and work productivity and activity among patients referred to secondary care for treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough. Work productivity and activity is measured using the Work Productivity and Activity Impairment Questionnaire which is a 6-item self-administered questionnaire used to assess productivity and impairment because of a specific health problem such as chronic cough.	3 months