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

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

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.

Study Overview

• Status: Recruiting
• Conditions: COPD
• Intervention / Treatment: Combination product: Sputum-guided management and comprehensive care management; Other: Usual Care

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 128
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Terence N Ho, MB, MSc; Phone Number: 32995 9055221155; Email: hot4@mcmaster.ca
• Study Contact Backup: Name: Joshua Wald, MD; Phone Number: 37036 9055221155; Email: joshua.wald@medportal.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Not yet recruiting
      • Hamilton General Hospital
      • Contact: Terence Ho, MB MSc; Phone Number: 32995 905-522-1155; Email: hot4@mcmaster.ca
    • Hamilton, Ontario, Canada, L8N 4A6
      • Recruiting
      • St. Joseph's Healthcare Hamilton
      • Contact: Terence Ho, MB MSc; Phone Number: 32995 9055221155; Email: hot4@mcmaster.ca
      • Principal Investigator: Terence Ho, MB MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sputum-guided management and comprehensive care management; 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; 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.
Active Comparator: Usual Care; 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; As per previous, this group will receive three follow-up visits with study pulmonologist and clinic personnel interventions.

What is the study measuring?

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
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
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
FEV1	Change in FEV1 between clinic visits 1 and 3.	16 weeks
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
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
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

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: St. Joseph's Healthcare Hamilton; Hamilton Health Sciences Corporation; Hamilton Academic Health Sciences Organization
• Investigators: Principal Investigator: Terence Ho, MB, MSc, St. Joseph's Healthcare Hamilton

Publications and helpful links

General Publications

• Nici L, ZuWallack R. Integrated Care in Chronic Obstructive Pulmonary Disease and Rehabilitation. COPD. 2018 Jun;15(3):223-230. doi: 10.1080/15412555.2018.1501671. Epub 2018 Sep 5.
• Bourbeau J, Bhutani M, Hernandez P, Marciniuk DD, Aaron SD, Balter M, et al. CTS position statement: Pharmacotherapy in patients with COPD-An update. Canadian Journal of Respiratory, Critical Care, and Sleep Medicine. 2017;1(4):222-41.
• Wilson AM, Nair P, Hargreave FE, Efthimiadis AE, Anvari M, Allen CJ; ELVIS Research Study Group. Lipid and smoker's inclusions in sputum macrophages in patients with airway diseases. Respir Med. 2011 Nov;105(11):1691-5. doi: 10.1016/j.rmed.2011.07.011. Epub 2011 Aug 9.
• Leigh R, Sharon RF, Efthimiadis A, Hargreave FE, Kitching AD. Diagnosis of left-ventricular dysfunction from induced sputum examination. Lancet. 1999 Sep 4;354(9181):833-4. doi: 10.1016/S0140-6736(99)80018-X.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2022
• Primary Completion (Estimated): September 27, 2024
• Study Completion (Estimated): October 27, 2024

Study Registration Dates

• First Submitted: May 13, 2021
• First Submitted That Met QC Criteria: May 13, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: COPD; Exacerbation; Sputum; Comprehensive care management
• Other Study ID Numbers: 13532

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: No