Dexamethasone Treatment for Sepsis-associated Acute Respiratory Distress Syndrome: a Multicenter, Randomised, Double-blinded, Controlled Trial

Phase 3RecruitingNCT07576660

Southeast University, China1,704 enrolled

Overview

Acute respiratory distress syndrome (ARDS) is a major cause of acute hypoxemic respiratory failure in critically ill patients and is associated with substantial mortality. Current management is largely supportive, and no pharmacologic therapy has been shown consistently to reduce mortality in a broad population of patients with ARDS. Inflammation plays a central role in the pathogenesis of ARDS. Excessive inflammatory activation contributes to alveolar-capillary injury, impaired gas exchange, and progression of organ dysfunction. Glucocorticoids may mitigate these processes and have been associated in some studies with improved clinical outcomes, including shorter duration of mechanical ventilation. However, the effect of glucocorticoids on survival remains uncertain. ARDS is a heterogeneous syndrome with diverse etiologies, and treatment response may vary according to the underlying cause. A post hoc analysis of the Dex-ARDS trial suggested that the treatment effect of glucocorticoids may be greater in ARDS caused by pneumonia or extrapulmonary sepsis. In a cross-sectional survey of 135 patients with ARDS from 20 ICUs in China, pneumonia- and extrapulmonary sepsis-associated ARDS accounted for 77.6% of cases, indicating that these are the predominant etiologic subtypes encountered in clinical practice in China. More importantly, compared with ARDS attributable to other causes, pneumonia- and extrapulmonary sepsis-associated ARDS has been associated with higher mortality, suggesting a greater disease burden, worse prognosis, and a more urgent need for improved treatment strategies. On this basis, the present trial will enroll patients with ARDS caused by sepsis, including pneumonia and extrapulmonary sepsis. The primary hypothesis of this study is that, among patients with sepsis-associated ARDS, dexamethasone plus usual care, as compared with placebo plus usual care, will reduce 90-day all-cause mortality. We therefore designed a multicenter, randomized, double-blind, controlled trial to evaluate the clinical efficacy of dexamethasone in patients with sepsis-associated ARDS. The primary objective is to compare dexamethasone plus usual care with placebo plus usual care with respect to 90-day all-cause mortality.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Interventions

DexamethasoneDRUG

Participants assigned to dexamethasone will receive 20 mg intravenously as soon as possible after randomization. Beginning after 10:00 am on the next calendar day following randomization, dexamethasone 20 mg will be administered once daily through day 5, followed by dexamethasone 10 mg once daily from Day 6 to Day 10.

PlaceboDRUG

Participants assigned to the placebo group will receive 0.9% sodium chloride injection as matching placebo, administered according to the same schedule as dexamethasone

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age 18 years or older 2. Suspected or confirmed infection 3. Receipt of invasive mechanical ventilation with a positive end-expiratory pressure (PEEP) of at least 5 cm H₂O, noninvasive positive-pressure ventilation with a PEEP of at least 5 cm H₂O, or high-flow nasal oxygen therapy with a flow rate of at least 30 L/min 4. Acute-onset ARDS, defined as ARDS diagnosed for at least 6 hours but no more than 72 hours, according to the following criteria: (1) New or worsening respiratory symptoms or respiratory failure (2) Pulmonary infiltrates on chest radiography or computed tomography, or B-lines or consolidation on lung ultrasonography, not fully explained by pleural effusion, lobar or whole-lung collapse or atelectasis, or pulmonary nodules. Patients with unilateral pulmonary infiltrates, B-lines, or consolidation are eligible (3) Respiratory failure not fully explained by cardiac failure or fluid overload (4) Hypoxemia defined as PaO₂/FiO₂ of 300 mm Hg or less, or SpO₂/FiO₂ of 315 or less, with SpO₂ no greater than 97%. Exclusion Criteria: 1. Pregnancy 2. Planned withdrawal of life-sustaining treatment within the next 24 hours 3. Current hospitalization for more than 7 days before screening; 4. Clinical improvement within the 48 hours before randomization, based on the investigator's overall assessment 5. Highly suspected or confirmed COVID-19 infection 6. Severe chronic obstructive pulmonary disease, defined as a PaCO₂ ≥ 60 mmHg in a stable condition, or the need for long-term oxygen therapy, excluding CPAP/BiPAP prescribed exclusively for sleep-disordered breathing. 7. Congestive heart failure (NYHA III-IV) 8. A definite clinical indication for high-dose corticosteroids at screening, defined as a maximum daily dose exceeding hydrocortisone 200 mg or an equivalent glucocorticoid dose 9. Contraindications to short-term dexamethasone, including untreated systemic fungal infection, active tuberculosis, active viral hepatitis, or major upper gastrointestinal bleeding 10. Known hypersensitivity to dexamethasone 11. Participation in another interventional clinical trial within the previous 30 days

Outcomes

Primary Outcomes

90-day all-cause mortality

The proportion of participants who die from any cause between randomization (day 0) and day 90 (inclusive)

Time frame: From randomization (day 0) to day 90 (inclusive)

Secondary Outcomes

Ventilator-free days through day 28

The number of days from randomization (day 0) to day 28 (inclusive) during which the patient is alive and successfully liberated from invasive mechanical ventilation

Time frame: From randomization (day 0) to day 28 (inclusive)

Vasopressor-free days through day 28

The number of days from randomization (day 0) to day 28 (inclusive) during which the patient is alive and successfully discontinued from vasopressor therapy

Time frame: From randomization (day 0) to day 28 (inclusive)

Renal replacement therapy-free days through day 28

The number of days from randomization (day 0) to day 28 (inclusive) during which the patient is alive and does not require renal replacement therapy

Time frame: From randomization (day 0) to day 28 (inclusive)

28-day all-cause mortality

The proportion of participants who die from any cause between randomization (day 0) and day 28 (inclusive)

Time frame: From randomization (day 0) to day 28 (inclusive)

In-hospital mortality

The proportion of participants who die from any cause between randomization (day 0) and hospital discharge (inclusive). If a patient remains hospitalized for more than 90 days, 90-day mortality will be used as in-hospital mortality

Time frame: Time Frame: From randomization (day 0) up to hospital discharge, assessed up to 90 days

6-month all-cause mortality

The proportion of participants who die from any cause between randomization (day 0) and 6 months (inclusive)

Time frame: From randomization (day 0) to 6 months (inclusive)

12-month all-cause mortality

The proportion of participants who die from any cause between randomization (day 0) and 12 months

Time frame: From randomization(day 0) to 12 months

Hospital-free days through day 90

The number of days from randomization (day 0) to day 90 (inclusive) during which the patient is alive and does not require hospitalization

Time frame: From randomization (day 0) to day 90 (inclusive)

Decision to withhold or withdraw active treatment during hospitalization

The proportion of participants in whom active treatment is withheld or withdrawn between randomization (day 0) and hospital discharge (inclusive)

Time frame: Time Frame: From randomization (day 0) up to hospital discharge, assessed up to 90 days

Telephone Interview for Cognitive Status-Modified (TICS-m)

Cognitive status was assessed using a Chinese modified version of the Telephone Interview for Cognitive Status-modified (TICS-m). Higher scores indicate better cognitive performance

Time frame: 90 days, 6 months and 12 months after randomization

Post-Traumatic Stress Disorder (PTSD)

Psychological outcomes will be assessed with the Post-traumatic Stress Disorder Checklist-Civilian Version (PCL-C, Chinese version). Respondents indicate how much they have been bothered by a symptom over the past month using a 5-point scale, with higher scores indicating more severe levels of PTSD.

Time frame: 90 days, 6 months and 12 months after randomization

Health-related quality of life (EQ-5D-5L)

Health-related quality of life assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) instrument at 90 days, 6months and 12 months after randomization. The EQ-5D-5L measures health across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

Time frame: 90 days, 6 months and 12 months after randomization

Functional Activities Questionnaire (FAQ)

Caregiver-reported outcome, higher scores indicating worse impairment.

Time frame: 90 days, 6 months, 12 months after randomization

Activities of daily living (ADL) score

Assessed using the Barthel Index, including feeding, bathing, grooming, dressing, bowel control, bladder control, toileting, chair/bed transfer, ambulation, and stair climbing, higher scores indicate greater independence.

Time frame: 90 days, 6 months, 12 months after randomization

Dexamethasone Treatment for Sepsis-associated Acute Respiratory Distress Syndrome: a Multicenter, Randomised, Double-blinded, Controlled Trial

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts