Sputum-guided Treatment With Comprehensive Care Management in COPD - A Randomized-controlled Trial

Study Overview
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Brief Summary
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Chronic obstructive pulmonary disease (COPD) is a lung condition affecting 1 in 6 Canadians and does not have a cure. Flare-ups of COPD are the most common reason someone goes to hospital in Canada. This is made worse because within 30-days of having a flare-up, 1 in 5 patients will come back to hospital for the same problem. Flare-ups of COPD often have many causes and these are different person to person. Sometimes it is related to behaviours such as smoking or not using medicines properly. Other times, it is from lung inflammation. Education programs that help people learn about their disease and maintain healthy behaviours, and using phlegm to decide on which medicines will be useful, have been studied separately and appear to work, but many people still have flare-ups. To help fix this problem, we need to look carefully at each patient, to make sure they are on the right medicine but also have the right behaviours and support to benefit from medical care. The goal of this project is to see if patients who are taught the right behaviours and have their lung inflammation controlled with the right medicines will have fewer COPD flare-ups than those who get normal care.

Detailed Description
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STRIVE is a randomized-controlled trial comparing a two-pronged intervention, including sputum-biomarker-directed treatment of airway inflammation, and comprehensive care management, to usual care, for COPD patients with frequent exacerbation from two sites. The intervention consists of 6-months of comprehensive care management (CCM) and sputum biomarker-directed treatment of airway inflammation, including hospital and clinic visits. Clinic visits will occur at 2, 6 and 16 weeks after hospital discharge. For the intervention group, the key elements of CCM will be provided, including case management, self-management education, and coordination of community/hospital resources (1). Spontaneous sputum biomarkers will be used to direct therapy at the time of AECOPD and during clinic visits after hospital discharge.

Official Title
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Sputum-guided Treatment With Comprehensive Care Management for Respiratory Improvement to Provide Value and Escalate Care - A Randomized-controlled Trial

Conditions
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COPD

Intervention / Treatment
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* Combination Product: Sputum-guided management and comprehensive care management
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >=2 exacerbations of COPD in the last 12-months, FEV1/FVC<0.7 or radiologic emphysema, with a >-10 pack-year smoking history Exclusion Criteria: severe mental illness not controlled by medication or life-expectancy less than 6-months

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sputum-guided management and comprehensive care management<br>The intervention consists of 6-months of CCM and sputum biomarker-directed treatment of airway inflammation, including hospital and clinic visits. Clinic visits at 2, 6, and 16 weeks. The key elements of CCM will be provided, including case management, self-management education, and coordination of community/hospital resources (1). Clinic nurse will review inhaler technique with the patient. Sputum (spontaneous) biomarkers will be measured with results used to direct therapy at the time of AECOPD and during clinic visits after hospital discharge, at both sites. | Combination Product: Sputum-guided management and comprehensive care management<br>* Those in the intervention group will have their treatment determined by the presence and type of airway inflammation whether during AECOPD or as part of clinic optimization. Corticosteroids are given for airway eosinophilia (sputum eosinophils >3%), and antibiotics for airway neutrophilia (sputum neutrophils ≥65% and total cells >10 million cells/gram) or a positive sputum culture. Specialized stains to identify aspiration (Oil Red O; (3)) and left ventricular dysfunction (Perl's Prussian blue; (4)) will guide swallowing assessment and cardiac work-up, respectively. If a sputum sample is not produced as an outpatient spontaneously, then sputum induction will be pursued 8 weeks after discharge. If there are no sputum samples to guide inhaler regimen, then it will be determined by the study physician guided by the Canadian Thoracic Society guidelines (2) if a sputum-guided regimen has not already been established.<br>|
| Active Comparator: Usual Care<br>This group will also receive clinic visits at 2, 6, and 16 weeks with a study physician, and also education material, inhaler technique assessment and education, and case management from the clinic personnel. The study physician will pursue further investigation and/or further intervention if they see fit. | Other: Usual Care<br>* As per previous, this group will receive three follow-up visits with study pulmonologist and clinic personnel interventions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe exacerbations of COPD | As defined by an acute worsening of respiratory symptoms requiring treatment with antibiotics or steroids associated with ER visit or hospitalization. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Moderate COPD Exacerbation | as defined by worsening of symptoms requiring the use of antibiotics or steroids without ER visit or hospitalization | 6 months | 
| Mild COPD Exacerbation | Defined as worsening of symptoms that were self-managed and resolved without systemic steroids or antibiotics; captured by Clinical COPD Questionnaire | 6 months | 
| COPD exacerbation associated with inflammation | Defined as an exacerbation (as defined previously) with an abnormal sputum cell count or sputum culture | 6 months | 
| Time to first COPD exacerbation associated with inflammation | Defined as time to an exacerbation (as defined previously) with an abnormal sputum cell count or sputum culture | 6 months | 
| Time to first COPD exacerbation | Defined as time to an exacerbation (as defined previously) | 6 months | 
| Change in Clinical COPD Questionnaire | Change in Clinical COPD Questionnaire between Week 0 and Week 26. | 26 weeks | 
| Change in COPD Assessment Test | Change in COPD Assessment Test between Week 0 and Week 26. | 26 weeks | 
| Change in Patient Health Questionnaire-9 | Change in Patient Health Questionnaire-9 between Week 0 and Week 26. | 26 weeks | 
| Change in General Anxiety Disorder-7 questionnaire | Change in General Anxiety Disorder-7 questionnaire between Week 0 and Week 26. | 26 weeks | 
| EQ-5D-5L questionnaire | Change in EQ-5D-5L between Week 0 and Week 26. | 26 weeks | 
| FEV1 | Change in FEV1 between clinic visits 1 and 3. | 16 weeks | 
| Sputum eosinophil percentage | Change in sputum eosinophil percentage between clinic visits 1 and 3 | 16 weeks | 
| Sputum neutrophil count | Change in sputum neutrophil count between clinic visits 1 and 3 | 16 weeks | 
| Sputum abnormalities rectified | The number of subjects who have their sputum abnormalities rectified will be recorded between clinics 1 and 3 | 16 weeks | 
| Use of oral or inhaled corticosteroid | Cumulative dose of oral and inhaled corticosteroid | 6 months | 
| Use of antibiotics | Cumulative courses of oral or intravenous antibiotics | 6 months | 
| Participant recruitment number | number of patients approached for recruitment during study | 2 years | 
| Reason for non-participation | reasons for non-participation during recruitment period | 2 years | 
| Clinic attendance | Number of clinic visits attended while enrolled in the study | 6 months | 
| Number of days to visit 1 | number of days to visit 1 from hospital discharge | Should fall within a 2-3 week window | 
| Number of clinic visits | Number of clinic visits patients attend during the 6 months that they are participating in the study | 6 months | 
| Patient care | number of nursing telephone calls initiated by the patient, number of adequate sputum samples collected, and the number referred to a smoking cessation program | study duration | 
| Side effects | Side effects will be captured by noting peak serum glucose levels and blood pressure measured in-hospital, and the occurrence of psychosis, candidiasis, C. difficile infection, and gastrointestinal upset as reported by the patient during clinic visits | 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Exacerbation, Comprehensive care management, Sputum