Blood Tests for COPD Flare-Ups

(Bidex Trial)

Overseen By Vanessa PJ Luks, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Hospital Research Institute

Must not be taking: Chronic glucocorticoids

Disqualifiers: Asthma, Severe bronchiectasis, Immunosuppression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether two simple blood tests (C-reactive protein and eosinophils) can reduce the need for steroids and antibiotics in people with chronic obstructive pulmonary disease (COPD) flare-ups while ensuring effective treatment. Participants will be divided into two groups: one guided by blood test results and another receiving standard care. The study aims to determine if this approach is feasible and effective for managing COPD flare-ups. It suits those with a known COPD diagnosis who experience increased respiratory symptoms requiring more medication. Participants must be willing to visit the clinic during a flare-up and have follow-up calls about their condition and medication use. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to understand how it can benefit more patients with COPD.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the study involves assessing medication use during COPD flare-ups, it's possible that you may need to adjust your medications as directed by the study doctor.

What is the safety track record for the blood tests used in this trial?

Research shows that blood tests like C-reactive protein (CRP) and eosinophils can assist doctors in making treatment decisions for COPD flare-ups. Studies have found that CRP levels can indicate bacterial infections, guiding doctors on when antibiotics are necessary and reducing unnecessary use. For instance, one study showed that individuals who used CRP results required fewer antibiotics than those who did not.

Eosinophils, a type of white blood cell, have also been studied in COPD. Research suggests that patients with higher eosinophil levels might need fewer treatments during flare-ups. These patients are often younger and less likely to have infections.

Both CRP and eosinophil tests are already used in other medical areas, providing some confidence in their safety. However, their use in COPD is relatively new. Studies suggest these tests are safe and do not seem to cause harm, but this trial will help confirm their safety and effectiveness in managing COPD flare-ups. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study?

Researchers are excited about using blood tests like C reactive protein (CRP) and eosinophil counts for managing COPD flare-ups because they offer a more personalized approach. Unlike the standard treatment, which often prescribes steroids and antibiotics based on symptoms alone, these tests provide specific biomarkers that can guide more precise medication choices. This method could reduce unnecessary steroid and antibiotic use, potentially lowering side effects and improving patient outcomes by tailoring treatments to the individual’s needs.

What evidence suggests that these blood tests are effective for managing COPD flare-ups?

This trial will compare biomarker-guided therapy using blood tests with standard care for COPD flare-ups. Research has shown that C-reactive protein (CRP) blood tests can reduce antibiotic use in patients with COPD flare-ups without causing harm. CRP helps doctors determine the necessity of antibiotics by checking for signs of bacterial infection. Studies found that CRP-guided treatment did not affect recovery but reduced unnecessary antibiotic use. Eosinophil levels, a type of white blood cell, in blood tests can guide steroid use for controlling inflammation. Together, these blood tests help ensure patients receive only the medications they truly need, making treatment safer and more effective. ^{6 7 8 9 10}

Who Is on the Research Team?

Vanessa PJ Luks, MD

Principal Investigator

OHRI

Are You a Good Fit for This Trial?

This trial is for outpatients with a confirmed diagnosis of COPD who are experiencing an increase in respiratory symptoms. They must have documented COPD by spirometry or specialist's diagnosis, and be willing to consent. Excluded are those with new lung infiltrates, high fever, positive blood culture on the day of randomization, co-morbid asthma or severe bronchiectasis, acute heart failure, known immunosuppression including chronic steroid use, allergy to oral steroids, or current/planned pregnancy.

Inclusion Criteria

Consent provided

I have COPD confirmed by a lung function test or a specialist.

My COPD symptoms have worsened, requiring more medication.

Exclusion Criteria

New infiltrate on chest x-ray day of randomization

Temperature ≥ 38.0 ◦C taken orally day of randomization

Planned pregnancy or currently pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive biomarker-guided or standard care treatment for AECOPD

4 weeks

1 in-person visit for randomization and treatment initiation

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

3 follow-up calls at days 3, 14, and 30

What Are the Treatments Tested in This Trial?

Interventions

• Blood Tests (C reactive protein and eosinophils)

Trial Overview The study tests if using two blood tests (C reactive protein and eosinophils) can guide decisions to reduce unnecessary antibiotics and steroids during COPD flare-ups without compromising treatment success. It's a feasibility study assessing participant recruitment over 12 months, medication adherence, protocol compliance, data completeness at study end and willingness to provide phlegm samples.

How Is the Trial Designed?

Group I: Intervention Arm Experimental Treatment 1 Intervention

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.

Group II: Standard of care arm Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Citations

1. publications.ersnet.org publications.ersnet.org/content/breathe/15/4/353

Can we use a biomarker to guide antibiotic treatment in ... C-reactive protein (CRP), B-type natriuretic peptide and procalcitonin (PCT) are useful biomarkers that have been investigated for this purpose. For instance, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7373624/

C-reactive protein testing to guide antibiotic prescribing for ... This review provides clear evidence that CRP testing can reduce the use of antibiotics in patients with AECOPD without causing harm.

3. bmcpulmmed.biomedcentral.com bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-022-01958-4

Biomarkers to guide the use of antibiotics for acute ... We identified 28 studies that included an assessment of serum C-reactive protein (CRP) to determine bacterial aetiology in AECOPD (Table 3).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9101830/

Biomarkers to guide the use of antibiotics for acute ... There is moderate evidence from heterogeneous studies that serum CRP and PCT are of value in differentiating bacterial from non-bacterial AECOPD.

5. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0251716

2-Day versus C-reactive protein guided antibiotherapy with ... Levofloxacin once daily for 2 days had similar efficacy compared to CRP-guided in AECOPD. This short course treatment decreased antibiotic consumption.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12005209/

Clinical Characteristics and Outcomes of Eosinophilic ... Eosinophilic exacerbations of COPD were found to affect a younger, less co-morbid population, were less likely to be associated with infection, require less ...

7. respiratory-research.biomedcentral.com respiratory-research.biomedcentral.com/articles/10.1186/s12931-021-01888-5

Stability of blood eosinophils in acute exacerbation of chronic ... This study aimed to evaluate the stability of blood eosinophils in hospitalized AECOPD and its relationship to clinical outcomes.

8. ejb.springeropen.com ejb.springeropen.com/articles/10.1186/s43168-024-00291-0

Elevated C-reactive protein and mortality risk among COPD ... However, those with both COPD and elevated CRP had a significantly higher risk of mortality (HR = 2.70, 95% CI = 1.08–6.81). Age, health ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002962915307096

C-Reactive Protein Levels Predict Bacterial Exacerbation ... In this study, our results suggest that CRP level (19.65 mg/L) is a good potential biomarker for the diagnosis of bacterial infections.

10. clinicaltrials.gov clinicaltrials.gov/study/NCT05286918

Antibiotic Stewardship in AECOPD Through CRP-Guided ... The results showed that patients in the CRP group reported less antibiotic use within 28 days of randomisation (57.0% vs. 77.4%, adjusted OR 0.31, 95% CI 0.20 ...