Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00201409
Status:
COMPLETED
Last Update Posted:
2015-12-29
First Post:
2005-09-12
Brief Title:
A Randomized Trial of GM-CSF in Patients With ALIARDS
Sponsor:
University of Michigan
Organization:
University of Michigan
Study Overview
Official Title:
A Randomized Trial of GM-CSF in Patients With ALIARDS
Status:
COMPLETED
Status Verified Date:
2015-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will test the hypothesis that administration of granulocyte-macrophage colony stimulating factor GM-CSF to patients with acute lung injuryacute respiratory distress syndrome ALIARDS will improve the clinical course and outcome by shortening the duration of mechanical ventilation for these patients
Detailed Description:
BACKGROUND
Respiratory failure due to ALIARDS remains a major health problem despite significant progress in intensive care unit care and ventilator management ALIARDS is characterized by unacceptably high mortality despite enormous expenditure of health care resources Survivors face long-term consequences that may affect their quality of life New therapies are needed to improve early survival and to decrease long-term sequelae of this syndrome GM-CSF is a naturally occurring cytokine that is present in the normal lung with important roles in pulmonary homeostasis GM-CSF is essential for normal maturation and function of alveolar macrophages resident inflammatory cells that are responsible for initial defense against pneumonia Alveolar epithelial cells line the gas exchange surface of the lung Acute lung injury and subsequent abnormal healing is linked to delayed repair of damage to the epithelium following initial injury This can then lead to pulmonary fibrosis GM-CSF has potent effects on alveolar epithelial cells promoting proliferation and limiting epithelial cell death Thus GM-CSF has a distinctive combination of activities that make it an excellent candidate for a therapeutic intervention in ALIARDS Preliminary studies for this project demonstrate that GM-CSF can protect experimental animals against acute lung injury can decrease susceptibility to pneumonia and is protective against pulmonary fibrosis following acute lung injury There is extensive experience with the administration of recombinant human GM-CSF to human patients this biological is approved by the FDA and has been well-tolerated in trials involving critically ill patients This project is based on the hypothesis that administration of GM-CSF will improve clinical outcomes for patients with ALIARDS
DESIGN NARRATIVE
With the assent of the attending physician informed consent will be obtained from the patient or next of kin as soon as possible after case identification Physiologic measurements and specimen collection will begin at the time of entry into the study Three days after the patient has met criteria for ALIARDS or at entry into the study whichever is later heshe will be randomized to receive recombinant human GM-CSF 250 mcgM2 or placebo administered by slow intravenous infusion once daily for 14 days
This study will allow entry of patients who have fulfilled criteria for ALIARDS for up to 7 days Treatment will be initiated after patients have met criteria for at least 3 days Treatment with GM-CSF may prove both safe and effective within the first 1-2 days of lung injury However the present study will not address that question It is unlikely that the opportunity for improved outcome will be lost by delaying therapy for up to 3 days based on the proposed mechanisms by which GM-CSF might benefit this patient population Similarly the decision to treat for 14 days will allow for improved outcome in patients with non-resolving ARDS by reducing the incidence of ventilator-associated pneumonia and by decreasing pathologic fibroproliferation
The primary endpoint for this study will be the duration of mechanical ventilation Additional important endpoints will include changes in the severity of physiologic derangements of respiratory gas exchange non-respiratory organ failure and incidence of ventilator-associated pneumonia Additional assessments designed to determine the mechanism of benefit of GM-CSF treatment will include measures of lung epithelial cell integrity and measures of alveolar macrophage lung inflammatory cell function
Respiratory failure due to ALIARDS remains a major health problem despite significant progress in intensive care unit care and ventilator management ALIARDS is characterized by unacceptably high mortality despite enormous expenditure of health care resources Survivors face long-term consequences that may affect their quality of life New therapies are needed to improve early survival and to decrease long-term sequelae of this syndrome GM-CSF is a naturally occurring cytokine that is present in the normal lung with important roles in pulmonary homeostasis GM-CSF is essential for normal maturation and function of alveolar macrophages resident inflammatory cells that are responsible for initial defense against pneumonia Alveolar epithelial cells line the gas exchange surface of the lung Acute lung injury and subsequent abnormal healing is linked to delayed repair of damage to the epithelium following initial injury This can then lead to pulmonary fibrosis GM-CSF has potent effects on alveolar epithelial cells promoting proliferation and limiting epithelial cell death Thus GM-CSF has a distinctive combination of activities that make it an excellent candidate for a therapeutic intervention in ALIARDS Preliminary studies for this project demonstrate that GM-CSF can protect experimental animals against acute lung injury can decrease susceptibility to pneumonia and is protective against pulmonary fibrosis following acute lung injury There is extensive experience with the administration of recombinant human GM-CSF to human patients this biological is approved by the FDA and has been well-tolerated in trials involving critically ill patients This project is based on the hypothesis that administration of GM-CSF will improve clinical outcomes for patients with ALIARDS
DESIGN NARRATIVE
With the assent of the attending physician informed consent will be obtained from the patient or next of kin as soon as possible after case identification Physiologic measurements and specimen collection will begin at the time of entry into the study Three days after the patient has met criteria for ALIARDS or at entry into the study whichever is later heshe will be randomized to receive recombinant human GM-CSF 250 mcgM2 or placebo administered by slow intravenous infusion once daily for 14 days
This study will allow entry of patients who have fulfilled criteria for ALIARDS for up to 7 days Treatment will be initiated after patients have met criteria for at least 3 days Treatment with GM-CSF may prove both safe and effective within the first 1-2 days of lung injury However the present study will not address that question It is unlikely that the opportunity for improved outcome will be lost by delaying therapy for up to 3 days based on the proposed mechanisms by which GM-CSF might benefit this patient population Similarly the decision to treat for 14 days will allow for improved outcome in patients with non-resolving ARDS by reducing the incidence of ventilator-associated pneumonia and by decreasing pathologic fibroproliferation
The primary endpoint for this study will be the duration of mechanical ventilation Additional important endpoints will include changes in the severity of physiologic derangements of respiratory gas exchange non-respiratory organ failure and incidence of ventilator-associated pneumonia Additional assessments designed to determine the mechanism of benefit of GM-CSF treatment will include measures of lung epithelial cell integrity and measures of alveolar macrophage lung inflammatory cell function
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P50HL074024 | NIH | None | httpsreporternihgovquickSearchP50HL074024 |