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

2026年8月31日 更新者：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.

調査の概要

状態

募集

条件

介入・治療

研究の種類

介入

入学 (推定)

1704

段階

  • フェーズ 3

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究場所

  • 中国
      • Nanjing、中国
        • 募集
        • Zhongda Hospital, School of Medicine, Southeast University
        • コンタクト：
    • Jiangsu
      • Nanjing、Jiangsu、中国、210009
        • まだ募集していません
        • Zhongda Hospital, School of Medicine, Southeast University
        • コンタクト：

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 子
  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

説明

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

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：4倍

武器と介入

参加者グループ / アーム
介入・治療
実験的：Dexamethasone Group
Dexamethasone plus usual care
薬：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.
他の名前：
  • Dexamethasone sodium phosphate injection, 5 mg/1 mL
プラセボコンパレーター：Placebo Group
Placebo plus usual care
薬：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

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
90-day all-cause mortality
時間枠：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)

二次結果の測定

結果測定
メジャーの説明
時間枠
Ventilator-free days through day 28
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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)

その他の成果指標

結果測定
メジャーの説明
時間枠
Incidence of weaning success through day 28
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Southeast University, China

捜査官

  • 主任研究者：Jianfeng Xie, MD、Southeast University, Zhongda Hospital

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

  • [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.

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2026年8月27日

一次修了 (推定)

2029年9月30日

研究の完了 (推定)

2030年9月30日

試験登録日

最初に提出

2026年4月25日

QC基準を満たした最初の提出物

2026年5月4日

最初の投稿 (実際)

2026年5月8日

学習記録の更新

投稿された最後の更新 (実際)

2026年9月2日

QC基準を満たした最後の更新が送信されました

2026年8月31日

最終確認日

2026年6月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • DEFEND Trial

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

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いいえ

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いいえ

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