Eosinophil-driven Corticotherapy for Patients Hospitalized for COPD Exacerbation (eo-Drive)

University Hospital Center (CHU)

Status and phase: Enrolling; Phase 3

Conditions: COPD Exacerbation

Treatments: Drug: 5 days of placebo; Drug: 5 days of systemic corticotherapy (prednisone)

Study type: Interventional

Funder types: Other

Identifiers

NCT04234360

2019-002724-33 (EudraCT Number)

LIC-18-18-0374 (Other Grant/Funding Number)

RECHMPL19_0069 UF 7771

Details and patient eligibility

About

The primary objective of this study is to compare treatment failure rates between a group of eosinophilic (eosinophilia > 2% on day 1 of hospitalization) patients hospitalised for a COPD exacerbation treated via corticotherapy versus a similar group treated via placebo.

Secondarily, treatment failure rates will also be compared between a group of non-eosinophilic patients hospitalised for a COPD exacerbation treated via corticotherapy versus a similar group treated via placebo. Study arms will also be compared for additional aspects of efficacy and safety:

• speed of recovery during the initial hospitalization;
• corticosteroid side effects / induced comorbidities;
• changes in symptoms and episodes of exacerbation;
• pulmonary function, oxygen use and ventilation;
• patient trajectories and resource use (e.g. survival, consults, episodes of hospitalization, medications);
• drug consumption (especially as relates to COPD management, exacerbations and induced comorbidities);
• health status, quality of life, activity/disability;
• patient safety / adverse events in general.

Eosinophilia thresholds optimizing the prediction of corticosteroid response and COPD outcomes will be re-evaluated. The relationships between corticosteroid response and key biomarkers (e.g. infectious groups) will be thoroughly explored, including within eosinophil strata. Potential gender subgroups differences will also be evaluated.

Finally, in prevision of further exploratory studies, a biological collection and an imaging library will be created in association with this protocol. The biological collection will be used to explore the genetic basis and physiology linked with treatment response, gender and patient trajectories. The image library will be used as a platform for the exploration of new imaging markers developed, for example, via machine learning and affiliated techniques.

Enrollment: 600 estimated patients

Sex: All

Ages: 40 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients admitted to a participating hospital (ward, ICU or emergency services) for an acute COPD exacerbation
• For patients with known COPD: COPD defined according to GOLD 2018 criteria: (1) Post-bronchodilator FEV1/FVC < 70% of predicted values; (2) > 10 pack years smoking history
• For incident COPD cases with no spirometric history: symptoms and exposure according to GOLD 2018 report will be considered for the diagnosis, but if the spirometric diagnosis is not confirmed during follow-up, then the patient will be excluded
• Signed consent has been obtained, or the appropriate emergency procedure (under French law) allows enrolment
• Subjects must be covered by public health insurance
• Patient available for 3 months of follow-up. Subjects must be able to attend all scheduled visits and to comply with all trial procedures.

Exclusion criteria

• Subject unable to read or write; language barrier
• Subject who is in a dependency or employment with the sponsor or investigator
• Pregnancy or lactation
• Patients who are prisoners or under other forms of judicial protection
• Patients under any kind of guardianship
• The patient has already participated in the present protocol
• The patient is participating in another interventional study or has done so in the past 3 months
• The patient is in an exclusion period determined by a previous study
• The patient has been taking long-term systemic corticosteroids for longer than 1 month prior to inclusion
• The patient has already received > 1 mg/kg of systemic corticotherapy in the past 48h
• Intubated-ventilated patient
• Administration of oral experimental drug is impossible
• Cancer within the last 12 months
• Current diagnosis of Asthma
• T2-inflammation targeting biologics (Benralizumab, reslizumab, mepolizumab, dupilumab) treatment
• Admitted for any other reason including, but not limited to, pulmonary embolism, pneumothorax, heart failure
• Known allergy to corticosteroids
• Consideration of a potential negative drug interaction with corticosteroids (at the investigator's discretion)
• White blood cell formula already performed and distributed to implicated teams
• Directives for limitation-of-care ("LATA" in French) already established
• SARS-Cov2 positive test carry out during the COPD exacerbation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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600 participants in 4 patient groups, including a placebo group

Eosinophil count > 2%; corticotherapy

Experimental group

Description:

Eosinophilic patients randomized to this arm will receive 5 days of corticotherapy.

Treatment:

Drug: 5 days of systemic corticotherapy (prednisone)

Eosinophil count <= 2%; corticotherapy

Experimental group

Description:

Non-eosinophilic patients randomized to this arm will receive 5 days of corticotherapy.

Treatment:

Drug: 5 days of systemic corticotherapy (prednisone)

Eosinophil count > 2%; placebo

Placebo Comparator group

Description:

Eosinophilic patients randomized to this arm will receive 5 days of placebo.

Treatment:

Drug: 5 days of placebo

Eosinophil count <= 2%; placebo

Placebo Comparator group

Description:

Non-eosinophilic patients randomized to this arm will receive 5 days of placebo.

Treatment:

Drug: 5 days of placebo