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

31 sierpnia 2026 zaktualizowane przez: Jianfeng Xie, Southeast University, China

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.

Przegląd badań

Status

Rekrutacyjny

Warunki

Interwencja / Leczenie

Typ studiów

Interwencyjne

Zapisy (Szacowany)

1704

Faza

  • Faza 3

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

Lokalizacje studiów

  • Chiny
      • Nanjing, Chiny
        • Rekrutacyjny
        • Zhongda Hospital, School of Medicine, Southeast University
        • Kontakt:
    • Jiangsu
      • Nanjing, Jiangsu, Chiny, 210009
        • Jeszcze nie rekrutacja
        • Zhongda Hospital, School of Medicine, Southeast University
        • Kontakt:

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

  • Dziecko
  • Dorosły
  • Starszy dorosły

Akceptuje zdrowych ochotników

Nie

Opis

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

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Poczwórny

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Dexamethasone Group
Dexamethasone plus usual care
Lek: Dexamethasone
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.
Inne nazwy:
  • Dexamethasone sodium phosphate injection, 5 mg/1 mL
Komparator placebo: Placebo Group
Placebo plus usual care
Lek: Placebo
Participants assigned to the placebo group will receive 0.9% sodium chloride injection as matching placebo, administered according to the same schedule as dexamethasone

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
90-day all-cause mortality
Ramy czasowe: From randomization (day 0) to day 90 (inclusive)
The proportion of participants who die from any cause between randomization (day 0) and day 90 (inclusive)
From randomization (day 0) to day 90 (inclusive)

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Ventilator-free days through day 28
Ramy czasowe: From randomization (day 0) to day 28 (inclusive)
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
From randomization (day 0) to day 28 (inclusive)
Vasopressor-free days through day 28
Ramy czasowe: From randomization (day 0) to day 28 (inclusive)
The number of days from randomization (day 0) to day 28 (inclusive) during which the patient is alive and successfully discontinued from vasopressor therapy
From randomization (day 0) to day 28 (inclusive)
Renal replacement therapy-free days through day 28
Ramy czasowe: From randomization (day 0) to day 28 (inclusive)
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
From randomization (day 0) to day 28 (inclusive)
28-day all-cause mortality
Ramy czasowe: From randomization (day 0) to day 28 (inclusive)
The proportion of participants who die from any cause between randomization (day 0) and day 28 (inclusive)
From randomization (day 0) to day 28 (inclusive)
In-hospital mortality
Ramy czasowe: Time Frame: From randomization (day 0) up to hospital discharge, assessed up to 90 days
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: From randomization (day 0) up to hospital discharge, assessed up to 90 days
6-month all-cause mortality
Ramy czasowe: From randomization (day 0) to 6 months (inclusive)
The proportion of participants who die from any cause between randomization (day 0) and 6 months (inclusive)
From randomization (day 0) to 6 months (inclusive)
12-month all-cause mortality
Ramy czasowe: From randomization(day 0) to 12 months
The proportion of participants who die from any cause between randomization (day 0) and 12 months
From randomization(day 0) to 12 months
Decision to withhold or withdraw active treatment during hospitalization
Ramy czasowe: Time Frame: From randomization (day 0) up to hospital discharge, assessed up to 90 days
The proportion of participants in whom active treatment is withheld or withdrawn between randomization (day 0) and hospital discharge (inclusive)
Time Frame: From randomization (day 0) up to hospital discharge, assessed up to 90 days
Telephone Interview for Cognitive Status-Modified (TICS-m)
Ramy czasowe: 90 days, 6 months and 12 months after randomization
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
90 days, 6 months and 12 months after randomization
Post-Traumatic Stress Disorder (PTSD)
Ramy czasowe: 90 days, 6 months and 12 months after randomization
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.
90 days, 6 months and 12 months after randomization
Health-related quality of life (EQ-5D-5L)
Ramy czasowe: 90 days, 6 months and 12 months after randomization
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.
90 days, 6 months and 12 months after randomization
Functional Activities Questionnaire (FAQ)
Ramy czasowe: 90 days, 6 months, 12 months after randomization
Caregiver-reported outcome, higher scores indicating worse impairment.
90 days, 6 months, 12 months after randomization
Activities of daily living (ADL) score
Ramy czasowe: 90 days, 6 months, 12 months after randomization
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.
90 days, 6 months, 12 months after randomization
Hospital-free days through day 90
Ramy czasowe: From randomization (day 0) to day 90 (inclusive)
The number of days from randomization (day 0) to day 90 (inclusive) during which the patient is alive and does not require hospitalization
From randomization (day 0) to day 90 (inclusive)

Inne miary wyników

Miara wyniku
Opis środka
Ramy czasowe
Incidence of weaning success through day 28
Ramy czasowe: From randomization (day 0) to day 28 (inclusive)

For intubated patients, successful weaning was defined as survival without reintubation within 7 days after extubation, or liberation from invasive mechanical ventilation with ICU discharge within 7 days.

For tracheostomized patients, successful weaning was defined as spontaneous breathing via tracheostomy without mechanical ventilation for at least 7 consecutive days, or liberation from invasive mechanical ventilation with ICU discharge within 7 days.

Reintubation for diagnostic purposes (e.g., bronchoscopy) or planned surgical procedures (e.g., wound debridement, abdominal lavage, internal fixation of fractures, tracheostomy) was not considered weaning failure.
From randomization (day 0) to day 28 (inclusive)
Incidence of gastrointestinal bleeding through day 28
Ramy czasowe: From randomization (day 0) to day 28 (inclusive)
The proportion of participants who developed acute gastrointestinal bleeding requiring transfusion of more than 1 unit of packed red blood cells within 24 hours
From randomization (day 0) to day 28 (inclusive)
Incidence of secondary bloodstream infection through day 28
Ramy czasowe: From randomization (day 0) to day 28 (inclusive)
The proportion of participants who developed secondary bloodstream infection through day 28
From randomization (day 0) to day 28 (inclusive)
Incidence of VAP through day 28
Ramy czasowe: From randomization (day 0) to day 28 (inclusive)
The proportion of participants who developed ventilator-associated pneumonia through day 28
From randomization (day 0) to day 28 (inclusive)
Incidence of hyperglycemia events through day 28
Ramy czasowe: From randomization (day 0) to day 28 (inclusive)
The proportion of participants who had hyperglycemia events (blood glucose level >180 mg/dl) through day 28
From randomization (day 0) to day 28 (inclusive)

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Southeast University, China

Śledczy

  • Główny śledczy: Jianfeng Xie, MD, Southeast University, Zhongda Hospital

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

  • [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.

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

27 sierpnia 2026

Zakończenie podstawowe (Szacowany)

30 września 2029

Ukończenie studiów (Szacowany)

30 września 2030

Daty rejestracji na studia

Pierwszy przesłany

25 kwietnia 2026

Pierwszy przesłany, który spełnia kryteria kontroli jakości

4 maja 2026

Pierwszy wysłany (Rzeczywisty)

8 maja 2026

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

2 września 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

31 sierpnia 2026

Ostatnia weryfikacja

1 czerwca 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • DEFEND Trial

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

NIE

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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