Ignite Creation Date:
2024-07-17 @ 11:04 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06496997
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-15
First Post:
2024-07-04
Brief Title:
A Comparative Study of Glucocorticoids Efficacy in Acute Respiratory Distress Syndrome
Sponsor:
Fayoum University
Organization:
Fayoum University
Study Overview
Official Title:
A Comparative Study of Glucocorticoids Efficacy in Acute Respiratory Distress Syndrome
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
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:
The aim of the work is to compare the efficacy of equivalent doses of methylprednisolone dexamethasone and hydrocortisone in patients with ARDS
Detailed Description:
Acute respiratory distress syndrome ARDS is a secondary disease that follows-usually within 6-48 h-a primary disease of multifactorial etiology most frequently pneumonia and extrapulmonary sepsis associated with severe systemic inflammation Inflammatory mediators released into the systemic circulation systemic inflammation from the site of infection reach the broad pulmonary capillary surface producing severe and diffuse inflammatory exudate of the pulmonary lobules and resulting in hypoxemic respiratory failure
In ARDS systemic inflammation is activated by the nuclear factor-κB NF-κB signaling system and downregulated by activated glucocorticoid receptor α GRα In these patients inadequate endogenous glucocorticoid-activated GRα-mediated downregulation of proinflammatory transcription factor NF-κB in circulating and tissue cells leads to higher initial levels and persistent elevation over time of plasma and bronchoalveolar lavage markers of inflammation hemostasis and tissue repair Inadequate intracellular GRα-mediated anti-inflammatory activity for the severity of the patients illness was recently termed critical illness-related corticosteroid insufficiency CIRCI Experimental and clinical research shows that CIRCI can be improved with quantitatively and temporally adequate glucocorticoid administration
Glucocorticoids are commonly used in patients with acute respiratory distress syndrome ARDS or at-risk for ARDS with proposed mechanisms including reduction of local lung inflammation and dampening of systemic immune responses
Clinical trials of glucocorticoids in patients with ARDS or at-risk from a pulmonary infection have had mixed results with some studies suggesting benefit and others showing no beneficial effects Notably the glucocorticoid agent dose and duration has varied widely between studies increasing the challenge of interpreting discordant findings
In animal models of ARDS glucocorticoids decreased the expression of pro-inflammatory mediators in lung tissue including TNF-a IL-1a IL-1b IL-6 and IL-12 p40 and reduces lung injury through the reduction of oxygen radicals produced by neutrophils Beyond their anti-inflammatory effects during the acute phase of inflammation glucocorticoids also contributed to the resolution of inflammation trough reprogramming effects on macrophages
Glucocorticoids have been administered during two distinct phases of ARDS during the early stage of ARDS when inflammation is expected to be most important and during late phase of ARDS when lung fibrosis predominates The biological and pathological characteristics of these two entities differ greatly explaining the observed conflicting results in the effects of glucocorticoids in these two distinct conditions
The early phase of ARDS is characterized by major alveolar inflammation Thus glucocorticoids potent anti-inflammatory agents are theoretically expected to be relevant treatment for ARDS
Late-stage ARDS is characterized histologically by ongoing inflammation with fibroproliferation presence of hyaline membranes and persistent diffuse alveolar damage leading to prolonged mechanical ventilation and a higher risk of death The largest multicenter placebo-controlled trial found no evidence for beneficial effects of glucocorticoids initiated for late-stage ARDS
In ARDS systemic inflammation is activated by the nuclear factor-κB NF-κB signaling system and downregulated by activated glucocorticoid receptor α GRα In these patients inadequate endogenous glucocorticoid-activated GRα-mediated downregulation of proinflammatory transcription factor NF-κB in circulating and tissue cells leads to higher initial levels and persistent elevation over time of plasma and bronchoalveolar lavage markers of inflammation hemostasis and tissue repair Inadequate intracellular GRα-mediated anti-inflammatory activity for the severity of the patients illness was recently termed critical illness-related corticosteroid insufficiency CIRCI Experimental and clinical research shows that CIRCI can be improved with quantitatively and temporally adequate glucocorticoid administration
Glucocorticoids are commonly used in patients with acute respiratory distress syndrome ARDS or at-risk for ARDS with proposed mechanisms including reduction of local lung inflammation and dampening of systemic immune responses
Clinical trials of glucocorticoids in patients with ARDS or at-risk from a pulmonary infection have had mixed results with some studies suggesting benefit and others showing no beneficial effects Notably the glucocorticoid agent dose and duration has varied widely between studies increasing the challenge of interpreting discordant findings
In animal models of ARDS glucocorticoids decreased the expression of pro-inflammatory mediators in lung tissue including TNF-a IL-1a IL-1b IL-6 and IL-12 p40 and reduces lung injury through the reduction of oxygen radicals produced by neutrophils Beyond their anti-inflammatory effects during the acute phase of inflammation glucocorticoids also contributed to the resolution of inflammation trough reprogramming effects on macrophages
Glucocorticoids have been administered during two distinct phases of ARDS during the early stage of ARDS when inflammation is expected to be most important and during late phase of ARDS when lung fibrosis predominates The biological and pathological characteristics of these two entities differ greatly explaining the observed conflicting results in the effects of glucocorticoids in these two distinct conditions
The early phase of ARDS is characterized by major alveolar inflammation Thus glucocorticoids potent anti-inflammatory agents are theoretically expected to be relevant treatment for ARDS
Late-stage ARDS is characterized histologically by ongoing inflammation with fibroproliferation presence of hyaline membranes and persistent diffuse alveolar damage leading to prolonged mechanical ventilation and a higher risk of death The largest multicenter placebo-controlled trial found no evidence for beneficial effects of glucocorticoids initiated for late-stage ARDS
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None