Prednisone Reduction in ICU Patients With COPD Exacerbation (EoPred-ICU)

Eosinophil-guided Prednisone Administration in COPD Exacerbation Requiring Ventilatory Support

The aim of this multicenter, investigator-initiated, prospective, randomized, open-label, non-inferiority study is to evaluate a prednisone prescribing strategy, guided by eosinophil blood count compared to the standard (systematic) administration of corticosteroids, in patients with COPD exacerbation requiring ventilatory support.

Patients fulfilling inclusion criteria and consenting to participate in the study, will be randomized through a random table generated electronically, to eosinophil-guided group or to control group.

In the eosinophil-guided group, prednisone (1mg/kg/day for up to 5 days or during the hospital stay if less than 5 days) is administered only if the eosinophil count is >2%. If blood eosinophil count is ≤2%, no corticosteroids are given. In the control group: a treatment based on prednisone at a daily dose of 1 mg/kg will be routinely administered for a maximum of 5 days, or during the hospital stay, if it is less than 5 days. Corticosteroid treatment is taken in the morning in patients with NIV, and through the gastric tube in intubated patients.

The hypothesis tested is a non-inferiority of the "eosinophil-guided strategy" compared to the standard strategy, with less exposure to corticosteroids.

The primary endpoint is the proportion of unventilated patients at day 6 which is set to 50% in the control group. A pre-specified difference <10% would be a non-inferiority margin.

Secondary endpoints are: Number of ICU days alive without ventilatory support within 28 days after recruitment, length of stay in intensive care Unit, the intubation rate in patients initially under NIV, Mortality in the ICU, Hospital mortality.

Safety: New onset of diabetes or worsening of diabetes requiring the start or the increase in insulin therapy, Upper gastrointestinal bleeding (2 g drop of Hb requiring blood transfusion or fibroscopy), Uncontrolled hypertensive crisis requiring the introduction of new antihypertensives, ICU-acquired neuromyopathy, Nosocomial infection, Relapse rate / recurrence defined respectively by the rate of a new hospital consultation and/or admission in the week or the month following index hospitalization.

Sample size calculation: In a non-inferiority study, with an incidence of the event (no ventilation at D6) of 50% in the control group ( with 10% of acceptable difference for non-inferiority), a power of 80% and alpha error <0.05, it would take 86 patients per arm by anticipating 2% of lost sight.

Study Overview

• Status: Unknown
• Conditions: Mechanical Ventilation; Copd Exacerbation Acute
• Intervention / Treatment: Drug: Prednisone

Detailed Description

The aim of this multicenter, investigator-initiated, prospective, randomized, open-label, non-inferiority study is to evaluate a prednisone prescribing strategy guided by eosinophil blood count compared to the standard (systematic) administration of corticosteroids in patients with COPD exacerbation requiring ventilatory support,.

Consecutive patients admitted to the ICU with hypercapnic respiratory failure consecutive to COPD exacerbation, and requiring ventilatory support with non-invasive or invasive mechanical ventilation, will be considered for inclusion in the study.

Patients fulfilling inclusion criteria and consenting to participate in the study, will be randomized through a random table generated electronically, to eosinophil-guided group or to control group.

In eosinophil-guided group, patients will receive prednisone at a dose of 1mg/kg/day for up to 5 days or during the hospital stay if less than 5 days, only if the eosinophil count is> 2%,. Corticosteroid treatment is taken in the morning in patients with NIV, and through the gastric tube in intubated patients.If blood eosinophil count is ≤2%, no corticosteroids are given.

In the control group: A treatment based on prednisone at a daily dose of 1 mg/kg will be routinely administered for a maximum of 5 days, or during the hospital stay, if it is less than 5 days. Corticosteroid treatment is taken in the morning in patients with NIV, and through the gastric tube in intubated patients.

The associated medications will be administered in a standardized way The hypothesis tested is a non-inferiority of the "eosinophil-guided strategy" compared to the standard strategy, with less exposure to corticosteroids.

The primary endpoint is the proportion of unventilated patients at day 6 in study-groups which is set to 50% in the control group. A pre-specified difference <10% would be a non-inferiority margin.

Secondary endpoints are: Number of ICU days alive without ventilatory support within 28 days after recruitment, length of stay in intensive care Unit, the intubation rate in patients initially under NIV, Mortality in the ICU, Hospital mortality.

Safety:New onset of diabetes or worsening of diabetes requiring the start or the increase in insulin therapy, Upper gastrointestinal bleeding (2 g drop of Hb requiring blood transfusion or fibroscopy), Uncontrolled hypertensive crisis requiring the introduction of new antihypertensives, ICU-acquired neuromyopathy, Nosocomial infection, Relapse rate / recurrence defined respectively by the rate of a new hospital consultation and/or admission in the week or the month following index hospitalization.

Sample size calculation: In a non-inferiority study, with an incidence of the event (no ventilation at D6) of 50% in the standard group and this same incidence less than 60% (10% of acceptable difference for non-inferiority) , a power of 80% and alpha error <0.05, it would take 86 patients per arm by anticipating 2% of lost sight (http://www.pharmaschool.co/size8.asp).

• Study Type: Interventional
• Enrollment (Anticipated): 192
• Phase: Phase 4

Contacts and Locations

Study Locations

• Morocco
  • Marrakech, Morocco
    • Active, not recruiting
    • CHU Arrazi
  • Rabat, Morocco
    • Active, not recruiting
    • CHU Ibn Cina
• Tunisia
  • Mahdia, Tunisia, 5100
    • Recruiting
    • CHU Tahar Sfar
    • Contact: Souheil Elatrous, Prof; Phone Number: +21698403013; Email: souheil.elatrous@rns.tn
  • Monastir, Tunisia, 5000
    • Recruiting
    • CHU Fattouma Bourguiba
    • Contact: Lamia Ouanes-Besbes, Prof; Phone Number: +21673106013; Email: lamia.besbes@rns.tn
    • Contact: Fekri Abroug, Prof; Phone Number: +21673460672; Email: fekri.abroug@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with known or suspected COPD, and severe acute exacerbation of COPD, corresponding to an acute episode of exacerbation, associated with a hypercapnic respiratory failure (defined by RR> 25 cycles/min, Paco2> 6 kPa, and ph<7.35) requiring ICU admission for ventilatory support.

Exclusion Criteria:

• self-reported or physician-diagnosed asthma,
• life expectancy of less than 30 days,
• allergy to systemic corticosteroids,
• severe mental illness that could not be controlled by medication,
• severe language difficulties or the inability to provide a written informed consent,
• pneumonia or patent infection,
• systemic fungal infections, or
• patients receiving more than 10 mg of chronic systemic corticosteroids (prednisone equivalent) daily.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: eosinophil-guided group; patients will receive prednisone at a dose of 1mg/kg/day for up to 5 days or during the hospital stay if less than 5 days, only if the eosinophil count is> 2%	Drug: Prednisone; Corticosteroid treatment is taken in the morning in patients with NIV, and through the gastric tube in intubated patients
Active Comparator: control group; a treatment based on prednisone at a daily dose of 1 mg/kg will be routinely administered for a maximum of 5 days, or during the hospital stay, if it is less than 5 days	Drug: Prednisone; Corticosteroid treatment is taken in the morning in patients with NIV, and through the gastric tube in intubated patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of unventilated patients at day 6	patients breathing spontaneously by the 6th day following inclusion	day 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of ICU days alive without ventilatory support within 28 days after recruitment	number of days without MV by the 28th day	up to 28 days
intubation rate in patients initially under NIV	NIV failure	up to 28 days
hospital death	death during hospitalisation	up to 28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
serious adverse events	adverse events of prednisone	up to 28 days

Collaborators and Investigators

• Sponsor: Hôpital Universitaire Fattouma Bourguiba

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2019
• Primary Completion (Anticipated): March 31, 2020
• Study Completion (Anticipated): April 1, 2020

Study Registration Dates

• First Submitted: June 4, 2019
• First Submitted That Met QC Criteria: June 7, 2019
• First Posted (Actual): June 10, 2019

Study Record Updates

• Last Update Posted (Actual): June 10, 2019
• Last Update Submitted That Met QC Criteria: June 7, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: COPD; Steroids; Acute hypercapnic respiratory failure
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: P01RM2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No