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 |
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Copd Exacerbation Acute Mechanical Ventilation | Drug: Prednisone | Phase 4 |
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 (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 |
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
|
Ages Eligible for Study: | 40 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
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 |
Tracking Information | |||||
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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 |
proportion of unventilated patients at day 6 [ Time Frame: day 6 ] patients breathing spontaneously by the 6th day following inclusion
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | No Changes Posted | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures |
serious adverse events [ Time Frame: up to 28 days ] adverse events of prednisone
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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. |
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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). |
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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 |
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Condition ICMJE |
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Intervention ICMJE | Drug: Prednisone
Corticosteroid treatment is taken in the morning in patients with NIV, and through the gastric tube in intubated patients
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Unknown status | ||||
Estimated Enrollment ICMJE |
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:
Exclusion Criteria:
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Sex/Gender ICMJE |
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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 |
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IPD Sharing Statement ICMJE |
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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 |