Do Blood Tests Help to Decide Which Patients With Flares of Chronic Obstructive Pulmonary Disease (COPD) Need Antibiotics and Steroids?

NCT06929767 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 20240689-01H
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to see if the use of two simple blood tests: C reactive protein and eosinophils, can reduce the use of steroids and antibiotics in patients with flares of chronic obstructive pulmonary disease (COPD) without reducing the chance of treatment success. Before we undertake a large trial to answer these questions, we need to do a small feasibility study to see if our study design will work. The questions we need to answer include: How many participants will we able to include in the study over 12 months? How many participants in the trial will take all of their medications? Will study protocols be followed? How much information will we be missing at the end of the study? How many study participants will take photographs of the phlegm they are coughing up or bring in a sample of the phlegm for inspection by study doctor? Participants will: Come into the clinic to be assessed when they have a flare of COPD, get a chest x-ray, blood work, and a doctor visit. The doctor will provide a prescription if it is a flare of COPD. The participant will get a call 3, 14, and 30 days later by a study researcher to ask questions about if the medications have been taken, if cough or shortness of breath remain, and if they have had to seek additional care from another doctor, clinic, or emergency room.

Conditions

Chronic Obstructive Pulmonary Disease; COPD; Exacerbation of COPD; AECOPD; ECOPD

Keywords

bio-maker; C reactive protein; CRP; eosinophils; exacerbation; COPD exacerbation; AECOPD; biomarker

Outcome Measures

Primary Outcomes (1)

• The primary objective of this study is to determine the number of patients screened, enrolled, and randomized within a 12-month period.

  We need to know if this is a study that patients would want to do, and if this is a study that physicians would be willing to enroll or refer patients to. * number screened: an absolute count of patients who are contacted by the RA for initial screening and information * proportion enrolled: number of subjects who verbally consent divided by number of subjects screened * proportion randomized: number of subjects who had an exacerbation and were randomized divided by number of subjects enrolled

  12 months

Secondary Outcomes (5)

• To determine what proportion of patients had exacerbations after enrollment but prior to randomization, that were missed by the study.

  12 months

• To determine what proportion of physicians were adherent to the treatment recommendations provided.

  12 months

• To determine what percentage of patients would fall into each category: What percentage had blood eosinophils > = 2% ? What percentage had CRP > = 40? What percentage had CRP < 20? What percentage had purulent sputum ?

  12 months

• To determine what percentage of patients had taken a photograph of their sputum or brought sputum to be assessed in-person.

  12 months

• To determine how many patients had complete data collection.

  12 months

Study Arms (2)

Intervention Arm

OTHER

If randomized to the intervention arm (biomarker-guided therapy), the physician will be provided with the biomarker-guided recommendations and will access Epic to look at the patient's biomarkers. The physician will then write a Rx for the patient keeping these recommendations in mind (but not being bound by them). Patient allergies will be taken into account when writing the Rx. * if blood eosinophils are \>=2%, steroids are recommended * if blood eosinophils are \< 2%, steroids are not recommended (unless the patient also has CRP \< 20 with non-purulent sputum, then an abbreviated course of steroids can be considered) * if CRP is \>= 40 mg/L,or \>=20 with purulent sputum, antibiotics are recommended; if neither condition is met, antibiotics are not recommended.

Other: biomarker-guided decision making

Standard of care arm

ACTIVE COMPARATOR

If randomized to the control arm (standard of care) arm, the physician will write a prescription based on what they feel is standard of care (and will not look at the biomarker results). Patient allergies will be taken into account when writing the Rx. * standard of care recommendations based on most recent GOLD publication will be provided which currently include: * steroids in all patients with AECOPD * antibiotics only if there are 2 out of 3 cardinal symptoms (dyspnea, cough, sputum), and one of the symptoms has to be purulent sputum

Other: GOLD recommendations

Interventions

biomarker-guided decision making OTHER

-recommendations for antibiotic and steroid Rx provided to study physician based on bio-marker (serum CRP, blood eosinophils, sputum colour) results.

Intervention Arm

GOLD recommendations OTHER

Recommendations provided to study physician for Rx of antibiotics and steroids based on current GOLD recommendations

Standard of care arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Outpatients with a known diagnosis of COPD (must have prior spirometry documenting FEV1/FVC post-bronchodilator \< 0.7 or documented respirologist-diagnosis of COPD)
• Presenting with AECOPD, defined as an increase in respiratory symptoms necessitating an increase in medications
• Consent provided

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• new infiltrate on chest x-ray day of randomization
• temperature ≥ 38.0 ◦C taken orally day of randomization
• positive blood culture day of randomization
• co-morbid asthma or severe bronchiectasis
• acute heart failure day of randomization
• known immunosuppression including the use of chronic glucocorticoids day of randomization
• allergy/absolute contraindication to the use of oral steroids
• planned pregnancy or currently pregnant
• COVID positive

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Related Publications (18)

• Ramakrishnan S, Jeffers H, Langford-Wiley B, Davies J, Thulborn SJ, Mahdi M, A'Court C, Binnian I, Bright S, Cartwright S, Glover V, Law A, Fox R, Jones A, Davies C, Copping D, Russell RE, Bafadhel M. Blood eosinophil-guided oral prednisolone for COPD exacerbations in primary care in the UK (STARR2): a non-inferiority, multicentre, double-blind, placebo-controlled, randomised controlled trial. Lancet Respir Med. 2024 Jan;12(1):67-77. doi: 10.1016/S2213-2600(23)00298-9. Epub 2023 Nov 2.

  PMID: 37924830 BACKGROUND

• Bafadhel M, McKenna S, Terry S, Mistry V, Pancholi M, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, Brightling CE. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2012 Jul 1;186(1):48-55. doi: 10.1164/rccm.201108-1553OC. Epub 2012 Mar 23.

  PMID: 22447964 BACKGROUND

• Zhang K, Xie K, Zhang C, Liang Y, Chen Z, Wang H. C-reactive protein testing to reduce antibiotic prescribing for acute respiratory infections in adults: a systematic review and meta-analysis. J Thorac Dis. 2022 Jan;14(1):123-134. doi: 10.21037/jtd-21-705.

  PMID: 35242374 BACKGROUND

• Hoult G, Gillespie D, Wilkinson TMA, Thomas M, Francis NA. Biomarkers to guide the use of antibiotics for acute exacerbations of COPD (AECOPD): a systematic review and meta-analysis. BMC Pulm Med. 2022 May 13;22(1):194. doi: 10.1186/s12890-022-01958-4.

  PMID: 35549921 BACKGROUND

• C REACTIVE PROTEIN-GUIDED ANTIBIOTIC PRESCRIBING VS STANDARD OF CARE IN EXACERBATIONS OF COPD: A SYSTEMATIC REVIEW WITH META-ANALYSIS Luks, Vanessa et al. CHEST, Volume 158, Issue 4, A1788

  BACKGROUND

• Daniels JM, de Graaff CS, Vlaspolder F, Snijders D, Jansen HM, Boersma WG. Sputum colour reported by patients is not a reliable marker of the presence of bacteria in acute exacerbations of chronic obstructive pulmonary disease. Clin Microbiol Infect. 2010 Jun;16(6):583-8. doi: 10.1111/j.1469-0691.2009.02892.x. Epub 2009 Jul 20.

  PMID: 19681947 BACKGROUND

• Brusse-Keizer MG, Grotenhuis AJ, Kerstjens HA, Telgen MC, van der Palen J, Hendrix MG, van der Valk PD. Relation of sputum colour to bacterial load in acute exacerbations of COPD. Respir Med. 2009 Apr;103(4):601-6. doi: 10.1016/j.rmed.2008.10.012. Epub 2008 Nov 22.

  PMID: 19027281 BACKGROUND

• Stockley RA, O'Brien C, Pye A, Hill SL. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. Chest. 2000 Jun;117(6):1638-45. doi: 10.1378/chest.117.6.1638.

  PMID: 10858396 BACKGROUND

• Soler N, Esperatti M, Ewig S, Huerta A, Agusti C, Torres A. Sputum purulence-guided antibiotic use in hospitalised patients with exacerbations of COPD. Eur Respir J. 2012 Dec;40(6):1344-53. doi: 10.1183/09031936.00150211. Epub 2012 Apr 20.

  PMID: 22523352 BACKGROUND

• Chen K, Pleasants KA, Pleasants RA, Beiko T, Washburn RG, Yu Z, Zhai S, Drummond MB. Procalcitonin for Antibiotic Prescription in Chronic Obstructive Pulmonary Disease Exacerbations: Systematic Review, Meta-Analysis, and Clinical Perspective. Pulm Ther. 2020 Dec;6(2):201-214. doi: 10.1007/s41030-020-00123-8. Epub 2020 Jul 16.

  PMID: 32676981 BACKGROUND

• Li Z, Yuan X, Yu L, Wang B, Gao F, Ma J. Procalcitonin-guided antibiotic therapy in acute exacerbation of chronic obstructive pulmonary disease: An updated meta-analysis. Medicine (Baltimore). 2019 Aug;98(32):e16775. doi: 10.1097/MD.0000000000016775.

  PMID: 31393400 BACKGROUND

• Council of the Canadian Academies, 2019. When Antibiotics Fail. Ottawa (ON). The Expert Panel on the Potential Socio-Economic Impacts of Antimicrobial Resistance in Canada, Council of Canadian Academies.

  BACKGROUND

• Waljee AK, Rogers MA, Lin P, Singal AG, Stein JD, Marks RM, Ayanian JZ, Nallamothu BK. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ. 2017 Apr 12;357:j1415. doi: 10.1136/bmj.j1415.

  PMID: 28404617 BACKGROUND

• Bafadhel M, Davies L, Calverley PM, Aaron SD, Brightling CE, Pavord ID. Blood eosinophil guided prednisolone therapy for exacerbations of COPD: a further analysis. Eur Respir J. 2014 Sep;44(3):789-91. doi: 10.1183/09031936.00062614. Epub 2014 Jun 12. No abstract available.

  PMID: 24925917 BACKGROUND

• Wedzicha JA Ers Co-Chair, Miravitlles M, Hurst JR, Calverley PM, Albert RK, Anzueto A, Criner GJ, Papi A, Rabe KF, Rigau D, Sliwinski P, Tonia T, Vestbo J, Wilson KC, Krishnan JA Ats Co-Chair. Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2017 Mar 15;49(3):1600791. doi: 10.1183/13993003.00791-2016. Print 2017 Mar.

  PMID: 28298398 BACKGROUND

• Vollenweider DJ, Frei A, Steurer-Stey CA, Garcia-Aymerich J, Puhan MA. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2018 Oct 29;10(10):CD010257. doi: 10.1002/14651858.CD010257.pub2.

  PMID: 30371937 BACKGROUND

• Sethi S, Evans N, Grant BJ, Murphy TF. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 2002 Aug 15;347(7):465-71. doi: 10.1056/NEJMoa012561.

  PMID: 12181400 BACKGROUND

• Chen Y. Interpretation of Global Strategy for the Diagnosis, Treatment, Management and Prevention of Chronic Obstructive Pulmonary Disease 2022 Report. Vol. 25, Chinese General Practice. 2022.

  BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Vanessa PJ Luks, MD

  OHRI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanessa PJ Luks, MD

CONTACT

613-737-8198; vluks@toh.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Blinding: The assessing physician is not blinded to group allocation, but if randomized to standard of care, the physician does not access the biomarkers (or in other words the physician writes the Rx blinded to the CRP and blood eosinophil values). The patient is blinded to group allocation and their own biomarker values but not to the specific treatment. In order to ensure the patient cannot see their own bio-markers, these results will not be released to be shared with patients in the electronic medical record. The research assistant (also the outcome assessor) will be blinded to group allocation, and biomarker values, but not to specific treatment.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: We are studying the use of bio-markers to aide in decision-making for the prescription of pharmacotherapy in acute exacerbations of COPD (AECOPD). The intervention arm is using bio-markers to decide whether a patient should received antibiotics and/or steroids for their AECOPD. The control arm is using standard advice from GOLD (the Global Initiative for Obstructive Lung Disease) recommendations for prescription of therapy in AECOPD.

Study Record Dates

• First Submitted: April 8, 2025
• First Posted: April 16, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: April 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)