Clinical trial NCT06929767: Do Blood Tests Help to Decide Which Patients With Flares of Chronic Obstructive Pulmonary Disease (COPD) Need Antibiotics and Steroids?
Official title: Biomarker Guided Decision-making in Acute Exacerbation of COPD: a Feasibility Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
COPD
Exacerbation of COPD
AECOPD
ECOPD
Keywords: bio-maker
C reactive protein
CRP
eosinophils
exacerbation
COPD exacerbation
AECOPD
biomarker
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2025-04-16
Enrollment: 80
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: OTHER

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.

Detailed description: Study design: randomized, controlled, feasibility trial

Population: Adult patients with a physician diagnosis of COPD suffering from an acute exacerbation of COPD

Intervention: Recommendations for antibiotics and/or glucocorticoids based on CRP, peripheral blood eosinophils +/- sputum colour provided to treating physician.

Comparator: Recommendations for antibiotics and/or glucocorticoids based on current standard of care recommendations in the GOLD guidelines provided to treating physician.

Recruitment/Setting: Patients with COPD will be approached in the outpatient respiratory clinic at The Ottawa Hospital during a visit to see their treating respirologist. The nurse will identify COPD patients to the treating respirologist at the beginning of the visit using coloured flags in Epic. The respirologist will ask the patient if they would like to participate in this study. If they are interested, the patient will be referred to the clinical research assistant. Alternatively, the patient can self-refer by emailing or phoning the research number on the poster. The research assistant will follow-up with the patient via telephone to discuss preferred methods of communication to discuss the trial, updates, and do the informed consent. If applicable, the research assistant will have the patient fill out a consent to communicate via email form. If the research assistant cannot reach the patient via telephone, and they initially received an email, the research assistant may respond to the email with the request that the patient sign the consent to communicate via email before any additional information is provided to the patient.

Number of Centres Participating in the feasibility study: The Ottawa Hospital only for the feasibility study.

Consent: A meeting to have the consent discussion will be coordinated by the research assistant (RA) when they first call the patient or when the patient self-refers in response to the poster. The RA will set up a video conference via MS Teams, if this is not feasible for the patient, a telephone discussion will be done. The patient will receive a copy of the consent form in advance of the meeting via either MyChart Epic, email via MS 365 Share point (download link, encrypted file), fax to their fax machine or mail (whatever they prefer). Patients will be advised that although they have verbally agreed to the trial, written consent will be obtained, and they will be asked to sign the physical consent form at the time of the in-person study visit 1.

Study Procedures

After consent, the research coordinator will provide standard education to all patients on the symptoms of AECOPD, provide them with a checklist of symptoms of AECOPD, and a phone number to call should they meet criteria for AECOPD. This phone number will be operational 8am to 11am Monday to Friday to provide a same-day in-person visit with a study respirologist (that afternoon). The patients will also be contacted via telephone or email (depending on patient preference), on the first Monday of every month to remind them of the study number to call in the event of any exacerbation. The method of communication (email or phone call) will be determined by the RA at the consent meeting. The RA will also check Epic the first Monday of each month to see if the patient was prescribed any antibiotics or prednisone outside of the trial (suggesting patient exacerbations are being missed for randomization).

If the patient experiences an AECOPD:

The patient will call the number, and the research assistant will meet the patient at the study site (at a pre-arranged location). The patient will sign the consent form. A chest x-ray and blood work (CRP, CBC with differential) will be done immediately prior to seeing the study respirologist. The study respirologist will confirm that the patient is suffering from an AECOPD (by history and physical exam) and will confirm eligibility for randomization (including ruling out fever and reviewing the chest x-ray to rule out presence of pneumonia). At this point the patient will be randomized into the study. Baseline demographics will be collected at this time including age, smoking history, last FEV1, number of exacerbations in the last year, current chronic COPD medications, use of oxygen, any positive sputum cultures within the last year. The patients will also fill out a COPD Assessment Test (CAT) score (for comparison to future values). The CAT test takes \< 3 minutes to fill out.

The randomization process will consist of a computer-generated random listing of the two different treatment allocations blocked by variable blocks of two or four. Randomization will be through central allocation of a randomization schedule and will be coordinated by the Ottawa Health Research Institute.

After randomization, the treating physician will create a treatment prescription in Epic:

* 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 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.

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.

Assessments: Patients will be assessed at day 3, 14, and day 30 post-randomization by telephone by the clinical research assistant who is blinded to group allocation and biomarker values. At each call, requirement for additional visits for respiratory symptoms, completion of study medications, intensification or change of therapy, and the CAT will be administered. At day 3, if the patient feels worse, they will be advised to seek medical attention with their treating respirologist. The research assistant will also contact the treating respirologist to advise them of the worsening of a Bidex patient. At day 14, if the patient feels they have not improved, the research assistant will advise the patient to seek medical attention by calling their treating respirologist. The research assistant will also contact the treating respirologist to advise them of the lack of improvement of a patient enrolled in Bidex. At day 30, if the patient feels they have not improved, the research assistant will advise the patient to seek medical attention by calling their treating respirologist. The research assistant will also contact the treating respirologist to advise them of the lack of improvement of a patient enrolled in Bidex.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: The primary objective of this study is to determine the number of patients screened, enrolled, and randomized within a 12-month period.
timeFrame: 12 months
Secondary outcomes:
measure: To determine what proportion of patients had exacerbations after enrollment but prior to randomization, that were missed by the study.
timeFrame: 12 months
measure: To determine what proportion of physicians were adherent to the treatment recommendations provided.
timeFrame: 12 months
measure: 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 ?
timeFrame: 12 months
measure: To determine what percentage of patients had taken a photograph of their sputum or brought sputum to be assessed in-person.
timeFrame: 12 months
measure: To determine how many patients had complete data collection.
timeFrame: 12 months
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
Study officials:
affiliation: OHRI
name: Vanessa PJ Luks, MD
role: PRINCIPAL_INVESTIGATOR
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