Eosinophil-driven Corticotherapy for Patients Hospitalized for COPD Exacerbation

NCT04234360 | Unknown Phase 3 DMC

• 3 other identifiers: RECHMPL19_0069 UF 77712019-002724-33LIC-18-18-0374
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 22

Brief Summary

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.

Conditions

COPD Exacerbation

Outcome Measures

Primary Outcomes (1)

• Treatment failure

  Treatment failure for the primary outcome is defined according to Niewoehner et al. (1999) as death from any cause or need for intubation and mechanical ventilation, readmission due to COPD, or intensification of pharmacologic therapy (defined as the prescription of open-label systemic glucocorticoids, high-dose inhaled glucocorticoids (more than eight puffs per day of triamcinolone acetonide or its equivalent), theophylline, or any combination of these three therapies) at three months. In addition, an investigator meeting determined additional components of treatment failure that should be added to Niewoehner's definition in order to bring it up-to-date : * Initiation of non-invasive ventilation for \>24h after first treatment administration * Transfer to intensive care or indication for a transfer to intensive care. Incident limitations-of-care that can affect treatment failure should also be carefully noted.

  3 months

Secondary Outcomes (76)

• The speed of initial recovery: Time elapsed before showing signs of improvement

  During initial hospitalization (expected maximum of 28 days)

• The speed of initial recovery: Time elapsed in acidosis/hypercapnia

  During initial hospitalization (expected maximum of 28 days)

• The speed of initial recovery: Time elapsed before meeting pre-defined discharge criteria

  During initial hospitalization (expected maximum of 28 days)

• Presence /absence of comorbidities or steroid side effects: glycemia

  During initial hospitalization (expected maximum of 28 days)

• Presence /absence of comorbidities or steroid side effects: glycemia

  1 month

Other Outcomes (13)

• Blood differential

  Baseline (day 0)

• Blood differential

  day 2

• Blood differential

  On hospital discharge (expected maximum of 28 days)

Study Arms (4)

Eosinophil count > 2%; corticotherapy

EXPERIMENTAL

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

Drug: 5 days of systemic corticotherapy (prednisone)

Eosinophil count <= 2%; corticotherapy

EXPERIMENTAL

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

Drug: 5 days of systemic corticotherapy (prednisone)

Eosinophil count > 2%; placebo

PLACEBO COMPARATOR

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

Drug: 5 days of placebo

Eosinophil count <= 2%; placebo

PLACEBO COMPARATOR

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

Drug: 5 days of placebo

Interventions

5 days of systemic corticotherapy (prednisone) 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; Eosinophil count > 2%; corticotherapy

5 days of placebo 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; Eosinophil count > 2%; placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (22)

CHU Amiens

Amiens, France

NOT YET RECRUITING

CHU Brest - Hôpital Caval Blanche

Brest, France

RECRUITING

Clinique du Parc

Castelnau-le-Lez, France

NOT YET RECRUITING

Centre hospitalier intercommunal de Créteil

Créteil, France

WITHDRAWN

CH Libourne

Libourne, France

NOT YET RECRUITING

CHRU Lille

Lille, France

WITHDRAWN

Hospice Civils de Lyon

Lyon, France

RECRUITING

APHM - Hôpital Nord

Marseille, France

RECRUITING

CHU Montpellier

Montpellier, France

RECRUITING

CHU Nancy

Nancy, France

RECRUITING

CHU Nîmes

Nîmes, France

NOT YET RECRUITING

APHP - Hopital Européen Georges Pompidou

Paris, France

RECRUITING

APHP - Hôpital BICHAT

Paris, France

RECRUITING

APHP - Hôpital Cochin

Paris, France

RECRUITING

APHP - Hôpital Universitaire Pitié-Salpétrière

Paris, France

RECRUITING

APHP - Hôpital Universitaire Pitié-Salpétrière

Paris, France

NOT YET RECRUITING

CHU Bordeaux - Hôpital Haut Lévêque

Pessac, France

RECRUITING

CHU Reims

Reims, France

NOT YET RECRUITING

CH Roubaix

Roubaix, France

WITHDRAWN

CHRU Strasbourg

Strasbourg, France

NOT YET RECRUITING

Hôpital Larrey CHU Toulouse

Toulouse, France

RECRUITING

Hôpital Nord Franche-Comté

Trévenans, France

COMPLETED

Related Publications (1)

• 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.

  PMID: 32611741 BACKGROUND

Related Links

• eo-Drive on the Open Science Framework

MeSH Terms

Interventions

Prednisone

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Arnaud BOURDIN

  a-bourdin@chu-montpellier.fr

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arnaud BOURDIN

CONTACT

0033467336126; a-bourdin@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients, investigators / outcome assessors / care givers and study staff are blinded to eosinophil / basophil / monocyte results and treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: January 13, 2020
• First Posted: January 21, 2020
• Study Start: October 12, 2021
• Primary Completion: October 12, 2024
• Study Completion: January 12, 2025
• Last Updated: January 26, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Datasets (and accompanying analytic code) can be requested after the publication process has been completed. The protocol, SAP and information materials will be made available in real-time (in as much as possible) on the study website at the Open Science Framework.
• Access Criteria: The conditions under which members of the public will be granted access to datasets are: * The data will be used/examined in a not-for-profit manner; * The data will not be used in an attempt to identify a participant or group of participants; * The user does not work for a private insurance company; * The data will not be used in support of any kind of private insurance policy or health penalties; * The data will be used/examined for the advancement of science/teaching while respecting participant/patient privacy and rights; * The user will state why they wish to access the data. * The appropriate CNIL approval has been obtained by the user.

Locations

FR (22)