The Effect of 6-Methyl-Prednisolone on Organ Dysfunction and Mortality of Patients With Unresolving Multiple Organ Dysfunction Syndrome
试验速览
- 阶段
- 4 期
- 入组人数
- 240
- 试验地点
- 6
- 主要终点
- All cause ICU and 28-day mortality
研究概览
简要总结
Background: Systemic corticosteroids are considered in patients with an adverse clinical course suffering from conditions like the acute respiratory distress syndrome (ARDS) and septic shock. Treated patients not only show improved respiratory function, but also hemodynamic status and overall multiple organ dysfunction score.
Objective: To evaluate the safety and effectiveness of 6-methyl-prednisolone on the clinical course of multiple organ dysfunction syndrome (MODS).
Design: Multi-center, double-blind, randomized, placebo-controlled.
Intervention: Intravenous administration of 6-methyl-prednisolone or placebo (aqueous solution). The duration of the study medication administration protocol is 32 days (1).
Primary Endpoints:
- All cause Intensive Care Unit (ICU) and 28-day mortality
- Organ dysfunction score on days 4, 7, 14, and 28 of the protocol.
详细描述
Background:
Worldwide intensive care physicians consider administering systemic corticosteroids in patients with an adverse clinical course suffering from conditions like the acute respiratory distress syndrome (ARDS) and septic shock. Data from recent small studies performed in patients with unresolving ARDS (1;2) suggest survival benefits associated with rescue therapy with relatively prolonged courses of corticosteroids. Treated patients not only show improved respiratory function, but also hemodynamic status and overall multiple organ dysfunction score. It has been suggested that that the integrity of the hypothalamic-pituitary-adrenal axis may be impaired in this patient subset (3;4)
Objective(s):
To evaluate the safety and effectiveness of a non-selective anti-inflammatory strategy, i.e. 6-methyl-prednisolone, on persistent and unresolving inflammatory states, i.e. multiple organ dysfunction syndrome, on the degree of organ dysfunction and mortality.
Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main Inclusion Criteria:
- •Patients with established, unresolving, refractory MODS, in whom all reversible and treatable causes of persistent MODS have been treated or ruled out:
- •Patients under endotracheal intubation and mechanical ventilation for at least 7 days.
- •Aggregate Multiple Organ Dysfunction Score (5) of greater than 8 over the first seven days of mechanical ventilation and greater than 5 on the day of inclusion.
- •Written informed consent to participate in the trial signed by next of kin or other authorized person.
- •Additional Inclusion Criteria:
- •Main cause or disease at admission: Adequate "source control" is required and refers to optimal, complete, and definitive surgical and/or medical therapy.
- •Infections:
- •Infectious causes of persistence of MODS have reasonably been ruled out on clinical or other grounds (infectious endocarditis, undrained abscesses like sinusitis, empyema or abdominal pus). Consider sampling for culture of broncho-alveolar lavage fluid, protected specimen brush or other (empyema fluid, lung tissue) in order to rule out respiratory infection, as well as intra-vascular catheter change and culture.
- •Present or previous infections, either documented or strongly suspected, have been treated for at least 3 days before inclusion.
- •Supportive Care: Optimal hemodynamic, renal, hematologic, nutritional "supportive care" is provided.
排除标准
- •Decision not to provide full support.
- •Immune status and steroid therapy.
- •Steroid therapy
- •Currently indicated for chronic or concurrent disease (meningitis, auto-immune disease, asthma, acute exacerbation of chronic obstructive pulmonary disease [COPD], or other). Inhaled steroids are allowed.
- •Administered during current admission (> 20 mg/day of 6-methyl-prednisolone or equivalent for >48 hours).
- •Chronic steroid therapy prior to current admission (> 20 mg of 6-methyl-prednisolone or equivalent/day for > 1 month during previous 3 months).
- •Other immune-suppressive therapy within the previous 6 months.
- •Known AIDS.
- •Neutropenia < 500/mcl.
- •Preceding organ transplantation.
- •Irreversible and or ultimately fatal clinical conditions like metastatic malignant disease or cardiogenic shock caused by coronary artery disease.
- •Presence of invasive fungal infection
- •Other significant pre-existing underlying chronic diseases:
- •Severe parenchymal liver disease (Child-Pugh grade C)
- •Severe and irreversible acute or chronic central nervous system disease.
- •Severe end-stage chronic obstructive pulmonary disease (home oxygen or more than 1 exacerbation in previous year)
- •End-stage renal disease (Chronic dialysis).
- •Age less than 18 years.
- •Pregnancy.
- •Morbid obesity: body mass index above
- •Recent (last 3 months) upper gastrointestinal [GI] hemorrhage.
- •Extensive burns (>30% body surface area [BSA])
- •Known allergy to steroids.
- •Written informed consent not available.
研究组 & 干预措施
Active
IV 6-methyl-prednisolone
干预措施: 6-methyl-prednisolone (Drug)
Comparator
IV Placebo
干预措施: 6-methyl-prednisolone (Drug)
结局指标
主要结局
All cause ICU and 28-day mortality
时间窗: 28 days
Organ dysfunction score on days 4, 7, 14, and 28 of the protocol
时间窗: Days 4, 7, 14, and 28.
次要结局
- Mortality(28 days)
- Morbidity: Duration of mechanical ventilation and endotracheal intubation (also a surrogate for acute steroid myopathy)(28 days)
- Length of ICU-stay(28 days)
- Complications of steroid therapy(28 days)
- Infections acquired during the protocol(28 days)
- Other complications (hyperglycemia, GI bleeding, acute myopathy, pneumothorax)(28 days)
- Adrenal reserve as evaluated by adrenocorticotropic hormone (ACTH) test.(Baseline)