Clinical trial NCT04758351: Prospective Study on the Evaluation, Patient Reported Outcomes and Effectiveness of Treatment for Chronic Cough
Official title: Prospective Study on the Evaluation, Patient Reported Outcomes and Effectiveness of Treatment for Chronic Cough in Secondary Care
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Cough
Keywords: Evaluation
Patient reported
Effectiveness
Treatment
Secondary Care
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Merck Canada Inc.
name: University of Manchester
name: University of British Columbia
First posted: 2021-02-17
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients referred to secondary care for investigation and treatment of explained chronic cough, refractory chronic cough, and unexplained chronic cough.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in objective cough frequency
timeFrame: 3 months
Secondary outcomes:
measure: Correlation in change of objective cough frequency and healthcare utilization
timeFrame: 3 months
measure: Correlation in change of objective cough frequency and lost productivity
timeFrame: 3 months
measure: Correlation in change of objective cough frequency and work productivity and activity
timeFrame: 3 months
measure: Correlation in change of quality of life and healthcare utilization
timeFrame: 3 months
measure: Correlation in change of quality of life and lost productivity
timeFrame: 3 months
measure: Correlation in change of quality of life and work productivity and activity
timeFrame: 3 months
measure: Patient satisfaction
timeFrame: 3 months
measure: Comparison of change in objective cough frequency and quality of life
timeFrame: 3 months
measure: Comparison of change in objective cough frequency and participant perceived change in condition
timeFrame: 3 months
measure: Measure the relationship between objective cough frequency and lost productivity
timeFrame: 3 months
measure: Measure the relationship between objective cough frequency and work productivity and activity
timeFrame: 3 months
Other outcomes:
measure: Correlation in exhaled nitric oxide, blood eosinophils, and sputum eosinophils and objective cough frequency and subjective patient reported outcomes
timeFrame: 3 months
measure: Changes in the quality of life
timeFrame: 3 months
measure: Changes in the perceived disease
timeFrame: 3 months
measure: Correlations between improved quality of life and perceived disease improvement
timeFrame: 3 months
Locations:
city: Hamilton
country: Canada
facility: Imran Satia
state: Ontario
Study officials:
affiliation: McMaster University
name: Imran Satia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.
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.
citation: 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.