Eosinophil-driven Corticotherapy for Patients Hospitalized for COPD Exacerbation

NCT ID: NCT04234360

Last Updated: 2024-01-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

600 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-12

Study Completion Date

2025-01-12

Brief Summary

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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.

Detailed Description

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Conditions

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COPD Exacerbation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a randomised (1:1), 2-parallel arm, double-blind trial comparing outcomes for a group of eosinophilic COPD patients (n=150) treated via corticotherapy versus a 2nd, similar group (n=150) treated via placebo. Secondarily, the same comparison (2x n=150) will be made for non-eosinophilic patients (totally excluding non-eosinophilic patients would potentially affect biomarker knowledge and subsequent care decisions, leading to bias).
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Patients, investigators / outcome assessors / care givers and study staff are blinded to eosinophil / basophil / monocyte results and treatment allocation.

Study Groups

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Eosinophil count > 2%; corticotherapy

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

Group Type EXPERIMENTAL

5 days of systemic corticotherapy (prednisone)

Intervention Type DRUG

Patients randomized to this arm will receive 40 mg prednisone per os per day for 5 days. Other aspects of standard, recommended care (e.g. antibiotherapy) are respected.

Eosinophil count <= 2%; corticotherapy

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

Group Type EXPERIMENTAL

5 days of systemic corticotherapy (prednisone)

Intervention Type DRUG

Patients randomized to this arm will receive 40 mg prednisone per os per day for 5 days. Other aspects of standard, recommended care (e.g. antibiotherapy) are respected.

Eosinophil count > 2%; placebo

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

Group Type PLACEBO_COMPARATOR

5 days of placebo

Intervention Type DRUG

Patients randomized to this arm will receive an appropriate placebo per os for 5 days. Other aspects of standard, recommended care (e.g. antibiotherapy) are respected.

Eosinophil count <= 2%; placebo

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

Group Type PLACEBO_COMPARATOR

5 days of placebo

Intervention Type DRUG

Patients randomized to this arm will receive an appropriate placebo per os for 5 days. Other aspects of standard, recommended care (e.g. antibiotherapy) are respected.

Interventions

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5 days of systemic corticotherapy (prednisone)

Patients randomized to this arm will receive 40 mg prednisone per os per day for 5 days. Other aspects of standard, recommended care (e.g. antibiotherapy) are respected.

Intervention Type DRUG

5 days of placebo

Patients randomized to this arm will receive an appropriate placebo per os for 5 days. Other aspects of standard, recommended care (e.g. antibiotherapy) are respected.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

40 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Montpellier

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Arnaud BOURDIN

Role: PRINCIPAL_INVESTIGATOR

[email protected]

Locations

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CHU Amiens

Amiens, , France

Site Status NOT_YET_RECRUITING

CHU Brest - Hôpital Caval Blanche

Brest, , France

Site Status RECRUITING

Clinique du Parc

Castelnau-le-Lez, , France

Site Status NOT_YET_RECRUITING

Centre hospitalier intercommunal de Créteil

Créteil, , France

Site Status WITHDRAWN

CH Libourne

Libourne, , France

Site Status NOT_YET_RECRUITING

CHRU Lille

Lille, , France

Site Status WITHDRAWN

Hospice Civils de Lyon

Lyon, , France

Site Status RECRUITING

APHM - Hôpital Nord

Marseille, , France

Site Status RECRUITING

CHU Montpellier

Montpellier, , France

Site Status RECRUITING

CHU Nancy

Nancy, , France

Site Status RECRUITING

CHU Nîmes

Nîmes, , France

Site Status NOT_YET_RECRUITING

APHP - Hopital Européen Georges Pompidou

Paris, , France

Site Status RECRUITING

APHP - Hôpital BICHAT

Paris, , France

Site Status RECRUITING

APHP - Hôpital Cochin

Paris, , France

Site Status RECRUITING

APHP - Hôpital Universitaire Pitié-Salpétrière

Paris, , France

Site Status RECRUITING

APHP - Hôpital Universitaire Pitié-Salpétrière

Paris, , France

Site Status NOT_YET_RECRUITING

CHU Bordeaux - Hôpital Haut Lévêque

Pessac, , France

Site Status RECRUITING

CHU Reims

Reims, , France

Site Status NOT_YET_RECRUITING

CH Roubaix

Roubaix, , France

Site Status WITHDRAWN

CHRU Strasbourg

Strasbourg, , France

Site Status NOT_YET_RECRUITING

Hôpital Larrey CHU Toulouse

Toulouse, , France

Site Status RECRUITING

Hôpital Nord Franche-Comté

Trévenans, , France

Site Status COMPLETED

Countries

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France

Central Contacts

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Arnaud BOURDIN

Role: CONTACT

0033467336126

Facility Contacts

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Claire ANDREJAK

Role: primary

Francis COUTURAUD

Role: primary

Marie GUEGAN

Role: backup

Khuder ALAGHA

Role: primary

Laurent PORTEL

Role: primary

Gilles DEVOUASSOUX

Role: primary

Pascal CHANEZ

Role: primary

Arnaud BOURDIN

Role: primary

Anne GUILLAUMOT

Role: primary

Nathalie PLOUVIER

Role: primary

Thibaud SOUMAGNE

Role: primary

Camille TAILLE

Role: primary

Nicolas ROCHE

Role: primary

Morgane FAURE

Role: primary

Jesus GONZALEZ

Role: primary

Maeva ZYSMAN

Role: primary

Gaétan DESLEE

Role: primary

Romain KESSLER

Role: primary

Elise NOEL-SAVINA

Role: primary

References

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Suehs CM, Zysman M, Chenivesse C, Burgel PR, Couturaud F, Deslee G, Berger P, Raherison C, Devouassoux G, Brousse C, Roche N, Molimard M, Chinet T, Devillier P, Chanez P, Kessler R, Didier A, Martinat Y, Le Rouzic O, Bourdin A. Prioritising outcomes for evaluating eosinophil-guided corticosteroid therapy among patients with acute COPD exacerbations requiring hospitalisation: a Delphi consensus study. BMJ Open. 2020 Jul 1;10(7):e035811. doi: 10.1136/bmjopen-2019-035811.

Reference Type BACKGROUND
PMID: 32611741 (View on PubMed)

Related Links

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https://osf.io/9j7uk/

eo-Drive on the Open Science Framework

Other Identifiers

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2019-002724-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LIC-18-18-0374

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

RECHMPL19_0069 UF 7771

Identifier Type: -

Identifier Source: org_study_id

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