A Factorial Trial of Glucocorticoid Therapy in Acute Respiratory Distress Syndrome: Optimizing Dosing Regimen and Developing Biomarker-guided Treatment
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 120
- 主要终点
- Ventilator-free survival
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Moderate to severe ARDS with a P/F ratio < 200 mmHg
- •On invasive mechanical ventilation
- •The onset of ARDS < 72 hours
排除标准
- •Age <20 years
- •Receiving systemic glucocorticoid therapy
- •Uncontrolled gastrointestinal bleeding
- •Terminal cancer
- •Post-operation or with large wound
- •Considered by the primary care doctor to be either definitely indicated or definitely contraindicated for glucocorticoid therapy
- •Anticipating to receive chemotherapy and immunotherapy in 3 months
- •Uncontrolled fungal infection
- •Post solid organ or bone marrow transplant
- •Severe influenza without anti-viral therapy
研究组 & 干预措施
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.
干预措施: Intravenous glucocorticoid therapy (Drug)
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.
干预措施: Intravenous glucocorticoid therapy (Drug)
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.
干预措施: Intravenous glucocorticoid therapy (Drug)
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.
干预措施: Intravenous glucocorticoid therapy (Drug)
结局指标
主要结局
Ventilator-free survival
时间窗: 28 days
Ventilator-free survival between control and intervention arms
次要结局
- Rapid oxygenation improvement(3 days)
- ICU mortality(Length of ICU stay up to 28 days)
- Blood glucose level(10 days)
- Hospital mortality(Length of hospital stay up to 60 days)
- Lymphocytopenia(7 days)
- Glucocorticoid treatment duration and ventilator-free survival(28 days)
- Successful liberation from mechanical ventilation(Up to 60 days)
- Hyperglycemia(10 days)
- Glucocorticoid dose and ventilator-free survival(28 days)
- 60-day mortality(60 days)
- Oxygenation on day 7(7 days)