Acute Respiratory Distress Syndrome (ARDS)Phase 3DEFENDNCT07576660
Dexamethasone Treatment for Sepsis-associated Acute Respiratory Distress Syndrome: a Multicenter, Randomised, Double-blinded, Controlled Trial
A Phase 3 study testing Dexamethasone in people with Acute Respiratory Distress Syndrome (ARDS), run by Southeast University, China at 2 sites in China.
Trial summary
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Respiratory Distress Syndrome (ARDS)
- What is being tested?
- Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,704 participants
- Where
- 2 sitesChina
- Study dates
- 27 Aug 2026to 30 Sep 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 18 years or older
- Suspected or confirmed infection
- 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
- Acute-onset ARDS, defined as ARDS diagnosed for at least 6 hours but no more than 72 hours, according to the following criteria:
- 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%.
Who cannot join
- Pregnancy
- Planned withdrawal of life-sustaining treatment within the next 24 hours
- Current hospitalization for more than 7 days before screening;
- Clinical improvement within the 48 hours before randomization, based on the investigator's overall assessment
- Highly suspected or confirmed COVID-19 infection
- 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.
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- Congestive heart failure (NYHA III-IV)
- 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
- Contraindications to short-term dexamethasone, including untreated systemic fungal infection, active tuberculosis, active viral hepatitis, or major upper gastrointestinal bleeding
- Known hypersensitivity to dexamethasone
- Participation in another interventional clinical trial within the previous 30 days
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Not yet recruiting
Zhongda Hospital, School of Medicine, Southeast University
Nanjing, Jiangsu, 210009
Jianfeng Xie, MD, +86-13770332331, xie820405@126.com
- Recruiting
Zhongda Hospital, School of Medicine, Southeast University
Nanjing
hui chen, MD, +86-18006138640, huichen.icu@gmail.com
About this study
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.
- Being tested
- Dexamethasone, Placebo
- Keywords
- Acute respiratory distress syndrome, Sepsis, Dexamethasone
- Medical subject headings
- Respiratory Distress Syndrome, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called Dexamethasone sodium phosphate injection, 5 mg/1 mL
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
| Study group | Role | What they receive |
|---|---|---|
| Dexamethasone Group | Experimental | Dexamethasone plus usual care Receives: Drug: Dexamethasone |
| Placebo Group | Placebo comparator | Placebo plus usual care Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
90-day all-cause mortality
The proportion of participants who die from any cause between randomization (day 0) and day 90 (inclusive)
Measured: From randomization (day 0) to day 90 (inclusive)
Secondary outcomes (14)
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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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)
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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.
Measured: 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.
Measured: 90 days, 6 months and 12 months after randomization
Functional Activities Questionnaire (FAQ)
Caregiver-reported outcome, higher scores indicating worse impairment.
Measured: 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.
Measured: 90 days, 6 months, 12 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2026
- Study start27 Aug 2026
- Primary completion30 Sep 2029 (estimated)
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress Syndrome (ARDS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,704 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Southeast University, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jianfeng Xie, Southeast University, China
- Investigators
- Jianfeng Xie, MD, Principal investigator, Southeast University, Zhongda Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07576660
- Sponsor's protocol ID
- DEFEND Trial
- Acronym
- DEFEND
- Status last verified
- Jun 2026
- First submitted
- 25 Apr 2026
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
[1] MATTHAY M A, ARABI Y, ARROLIGA A C, et al. A New Global Definition of Acute Respiratory Distress Syndrome[J]. American Journal of Respiratory and Critical Care Medicine, 2024, 209(1): 37-47. [2] BELLANI G, LAFFEY J G, PHAM T, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries[J]. JAMA, 2016, 315(8): 788. [3] LIU L, YANG Y, GAO Z, et al. Practice of diagnosis and management of acute respiratory distress syndrome in mainland China: a cross-sectional study[J]. Journal of Thoracic Disease, 2018, 10(9): 5394-5404. [4] MATTHAY M A, ZEMANS R L, ZIMMERMAN G A, et al. Acute respiratory distress syndrome[J]. Nature Reviews Disease Primers, 2019, 5(1): 18. [5] MEDURI G U, GOLDEN E, FREIRE A X, et al. Methylprednisolone infusion in early severe ARDS[J]. Chest, 2007, 131(4): 954-963. [6] ANNANE D, SÉBILLE V, BELLISSANT E. Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome*:[J]. Critical Care Medicine, 2006, 34(1): 22-30. [7] TONGYOO S, PERMPIKUL C, MONGKOLPUN W, et al. Hydrocortisone treatment in early sepsis-associated acute respiratory distress syndrome: Results of a randomized controlled trial[J]. Critical Care, 2016, 20(1): 329. [8] GRASSELLI G, CALFEE C S, CAMPOROTA L, et al. ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies[J]. Intensive Care Medicine, 2023, 49(7): 727-759. [9] VILLAR J, FERRANDO C, MARTÍNEZ D, et al. Dexamethasone treatment for the acute respiratory distress syndrome: A multicentre, randomised controlled trial[J]. The Lancet Respiratory Medicine, 2020, 8(3): 267-276. [10] CHRIGUER R S, ROSELINO A M, DE CASTRO M. Glucocorticoid sensitivity and proinflammatory cytokines pattern in pemphigus[J]. Journal of Clinical Immunology, 2012, 32(4): 786-793.