A Comparative Study of Glucocorticoids Efficacy in Acute Respiratory Distress Syndrome

NCT ID: NCT06496997

Last Updated: 2025-01-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-01
• Study Completion Date: 2025-09-30

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 patient's 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.

Conditions

Acute Respiratory Distress Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1

100 ARDS patients

Group Type: EXPERIMENTAL

Methylprednisolone

Intervention Type: DRUG

Methylprednisolone at a dose of 1 mg/kg/day (an average dose of 70 mg/day based on 70 kg body weight)

Group 2

100 ARDS patients

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: DRUG

Dexamethasone at an equivalent dose of 13 mg/day

Group 3

100 ARDS patients

Group Type: EXPERIMENTAL

Hydrocortisone

Intervention Type: DRUG

Hydrocortisone at an equivalent dose of 350 mg/day

Interventions

Methylprednisolone

Methylprednisolone at a dose of 1 mg/kg/day (an average dose of 70 mg/day based on 70 kg body weight)

Intervention Type: DRUG

Dexamethasone

Dexamethasone at an equivalent dose of 13 mg/day

Intervention Type: DRUG

Hydrocortisone

Hydrocortisone at an equivalent dose of 350 mg/day

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

We include patients receiving mechanical ventilation for hypoxemic respiratory failure if they met the diagnostic criteria for ARDS according to the American-European Consensus definition, as later reclassified on the basis of the 2012 Berlin criteria for the diagnosis of ARDS, defined as:

1. Presence of acute hypoxemic respiratory failure (an arterial oxygen partial pressure to fraction of inspired oxygen ratio (PaO2/FiO2) of ≤ 300 mm Hg, requiring supplemental oxygen administrated by simple face mask, nasal cannula, or other similar oxygen-delivery device to maintain oxygen saturation at greater than 93% within the first 48 h of the onset of ARDS)

2. Onset within 7 days of insult, or new (within 7 days) or worsening respiratory symptoms

3. Bilateral opacities on chest x-ray or CT not fully explained by effusions, lobar or lung collapse, or nodules

4. Cardiac failure not the primary cause of acute respiratory failure

Exclusion Criteria

We exclude patients with acute hypoxemic respiratory failure caused by congestive heart failure

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fayoum University

OTHER

Sponsor Role: lead

Responsible Party

Mahmoud Ezzat Musa Abdel Tawab

Teaching assistant in Clinical Pharmacy Department-Faculty of Pharmacy-Fayoum University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mahmoud Ezzat Elkmash, Teaching Assistant

Role: PRINCIPAL_INVESTIGATOR

Faculty of Pharmacy - Fayoum University

Raghda Roshdy Hussein, Assistant Professor

Role: STUDY_DIRECTOR

Faculty of Pharmacy - Beni Suef University

Marwa Kamal Tolba, Assistant Professor

Role: STUDY_DIRECTOR

Faculty of Pharmacy - Fayoum University

Marian Sobhi Saeed, Lecturer

Role: STUDY_DIRECTOR

Faculty of Pharmacy - Beni Suef University

Mona Ibrahim Ahmed, Lecturer

Role: STUDY_DIRECTOR

Faculty of Medicine - Fayoum University

Locations

Fayoum University

Al Fayyum, , Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Mahmoud Ezzat Elkmash, Teaching assistant

Role: CONTACT

mam54@fayoum.edu.eg

+201094123841

Marwa Kamal Tolba, Assistant Professor

Role: CONTACT

mka05@fayoum.edu.eg

+201067789982

Other Identifiers

Steroids Efficacy in ARDS

Identifier Type: -

Identifier Source: org_study_id