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出境医 / 临床实验 / Prednisone Reduction in ICU Patients With COPD Exacerbation (EoPred-ICU)

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

Study Description
Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Copd Exacerbation Acute Mechanical Ventilation Drug: Prednisone Phase 4

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 Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 192 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, multicenter, randomized, open-label, parallel groups
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Eosinophil-guided Prednisone Administration in COPD Exacerbation Requiring Ventilatory Support
Actual Study Start Date : April 2, 2019
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : April 1, 2020
Arms and Interventions
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

Outcome Measures
Primary Outcome Measures :
  1. proportion of unventilated patients at day 6 [ Time Frame: day 6 ]
    patients breathing spontaneously by the 6th day following inclusion


Secondary Outcome Measures :
  1. Number of ICU days alive without ventilatory support within 28 days after recruitment [ Time Frame: up to 28 days ]
    number of days without MV by the 28th day

  2. intubation rate in patients initially under NIV [ Time Frame: up to 28 days ]
    NIV failure

  3. hospital death [ Time Frame: up to 28 days ]
    death during hospitalisation


Other Outcome Measures:
  1. serious adverse events [ Time Frame: up to 28 days ]
    adverse events of prednisone


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations

Locations
Layout table for location information
Morocco
CHU Arrazi Active, not recruiting
Marrakech, Morocco
CHU Ibn Cina Active, not recruiting
Rabat, Morocco
Tunisia
CHU Tahar Sfar Recruiting
Mahdia, Tunisia, 5100
Contact: Souheil Elatrous, Prof    +21698403013    souheil.elatrous@rns.tn   
CHU Fattouma Bourguiba Recruiting
Monastir, Tunisia, 5000
Contact: Lamia Ouanes-Besbes, Prof    +21673106013    lamia.besbes@rns.tn   
Contact: Fekri Abroug, Prof    +21673460672    fekri.abroug@gmail.com   
Sponsors and Collaborators
Hôpital Universitaire Fattouma Bourguiba
Tracking Information
First Submitted Date  ICMJE June 4, 2019
First Posted Date  ICMJE June 10, 2019
Last Update Posted Date June 10, 2019
Actual Study Start Date  ICMJE April 2, 2019
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 7, 2019)
proportion of unventilated patients at day 6 [ Time Frame: day 6 ]
patients breathing spontaneously by the 6th day following inclusion
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2019)
  • Number of ICU days alive without ventilatory support within 28 days after recruitment [ Time Frame: up to 28 days ]
    number of days without MV by the 28th day
  • intubation rate in patients initially under NIV [ Time Frame: up to 28 days ]
    NIV failure
  • hospital death [ Time Frame: up to 28 days ]
    death during hospitalisation
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 7, 2019)
serious adverse events [ Time Frame: up to 28 days ]
adverse events of prednisone
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Prednisone Reduction in ICU Patients With COPD Exacerbation
Official Title  ICMJE Eosinophil-guided Prednisone Administration in COPD Exacerbation Requiring Ventilatory Support
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Prospective, multicenter, randomized, open-label, parallel groups
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Copd Exacerbation Acute
  • Mechanical Ventilation
Intervention  ICMJE Drug: Prednisone
Corticosteroid treatment is taken in the morning in patients with NIV, and through the gastric tube in intubated patients
Study Arms  ICMJE
  • 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%
    Intervention: Drug: Prednisone
  • 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
    Intervention: Drug: Prednisone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 7, 2019)
192
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 1, 2020
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Morocco,   Tunisia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03981081
Other Study ID Numbers  ICMJE P01RM2019
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Fekri Abroug, Hôpital Universitaire Fattouma Bourguiba
Study Sponsor  ICMJE Hôpital Universitaire Fattouma Bourguiba
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Hôpital Universitaire Fattouma Bourguiba
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP