Glucocorticoid Therapy for Acute Respiratory Distress Syndrome

A Factorial Trial of Glucocorticoid Therapy in Acute Respiratory Distress Syndrome: Optimizing Dosing Regimen and Developing Biomarker-guided Treatment

Acute respiratory distress syndrome (ARDS) is a clinical syndrome of inflammatory lung injury characterized by increased pulmonary vascular permeability, loss of aerated lung tissue, severe hypoxemia and impaired compliance. Despite the advance in the critical care technology, the mortality of ARDS remains high in the last decades. Glucocorticoids have profound anti-inflammatory actions through the pleiotropic effects of the glucocorticoid receptor, which are considering a promising pharmacological therapy to mitigate the inflammatory lung injury and subsequent fibrosis in ARDS. Previous clinical trials have repeatedly tested the efficacy of glucocorticoid therapy in ARDS; however, the data about hard outcomes, such as mortality, are inconsistent between these studies. Investigators designed a 3x2 factorial trial of glucocorticoid therapy in ARDS to test the effects of glucocorticoid dosages (dose 0, dose 0.5 mg/kg, and dose 1 mg/kg of methylprednisolone equivalence) and durations (prolonged and short duration) on the treatment efficacy. In addition, investigators will measure the change of inflammatory biomarkers for post-hoc analysis to explore whether biomarkers could be used to guide patient selection and steroid tapering.

Study Overview

• Status: Withdrawn
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Intravenous glucocorticoid therapy

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Moderate to severe ARDS with a P/F ratio < 200 mmHg
2. On invasive mechanical ventilation
3. The onset of ARDS < 72 hours

Exclusion Criteria:

1. Age <20 years
2. Receiving systemic glucocorticoid therapy
3. Uncontrolled gastrointestinal bleeding
4. Terminal cancer
5. Post-operation or with large wound
6. Considered by the primary care doctor to be either definitely indicated or definitely contraindicated for glucocorticoid therapy
7. Anticipating to receive chemotherapy and immunotherapy in 3 months
8. Uncontrolled fungal infection
9. Post solid organ or bone marrow transplant
10. Severe influenza without anti-viral therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Standard care without glucocorticoid therapy.
Experimental: Low dose and long treatment duration; Methylprednisolone equivalent dose 0.5 mg/kg/day for 5 days, followed by 0.25 mg/kg/day for 5 days.	Drug: Intravenous glucocorticoid therapy; Betamethasone, dexamethasone, or methylprednisolone
Experimental: Low dose and short treatment duration; Methylprednisolone equivalent dose 0.5 mg/kg/day for 4 days,, followed by 0.25 mg/kg/day for 3 days.	Drug: Intravenous glucocorticoid therapy; Betamethasone, dexamethasone, or methylprednisolone
Experimental: Moderate dose and long treatment duration; Methylprednisolone equivalent dose 1 mg/kg/day for 5 days, followed by 0.5 mg/kg/day for 5 days.	Drug: Intravenous glucocorticoid therapy; Betamethasone, dexamethasone, or methylprednisolone
Experimental: Moderate dose and short treatment duration; Methylprednisolone equivalent dose 1 mg/kg/day for 4 days, followed by 0.5 mg/kg/day for 3 days.	Drug: Intravenous glucocorticoid therapy; Betamethasone, dexamethasone, or methylprednisolone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-free survival	Ventilator-free survival between control and intervention arms	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucocorticoid dose and ventilator-free survival	Ventilator-free survival between low-dose and moderate-dose glucocorticoid groups	28 days
Glucocorticoid treatment duration and ventilator-free survival	Ventilator-free survival between long treatment duration and short treatment duration groups	28 days
ICU mortality	Between-group difference in mortality at ICU discharge	Length of ICU stay up to 28 days
Hospital mortality	Between-group difference in mortality at hospital discharge	Length of hospital stay up to 60 days
60-day mortality	Between-group difference in mortality by day 60	60 days
Oxygenation on day 7	Proportion of patients with a P/F ratio > 200 mmHg on day 7	7 days
Rapid oxygenation improvement	Change in P/F ratios between day 1 and day 3	3 days
Successful liberation from mechanical ventilation	Median time to successful liberation from mechanical ventilation	Up to 60 days
Lymphocytopenia	Proportion of lymphocytopenia on day 7	7 days
Blood glucose level	Peak blood glucose level during treatment	10 days
Hyperglycemia	Proportion of patients with hyperglycemia during treatment	10 days

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2022
• Primary Completion (Estimated): January 31, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: January 2, 2022
• First Submitted That Met QC Criteria: May 30, 2022
• First Posted (Actual): June 2, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 16, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Corticosteroid; Acute Respiratory Distress Syndrome; Glucocorticoid
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucocorticoids
• Other Study ID Numbers: 202012189MINB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No