A Randomised Blinded Placebo Controlled Trial of Hydrocortisone in Critically Ill Patients With Septic Shock
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 3,800
- 试验地点
- 70
- 主要终点
- All cause mortality at 90 days after randomisation
研究概览
简要总结
The purpose of this study is to find out whether adult patients admitted to the Intensive Care Unit with septic shock who are given hydrocortisone compared to placebo (a dummy solution), will have an improved rate of survival 90 days later.
Septic shock is the result of an infection, which triggers a complex response by the body (the inflammatory response) that causes a decrease in blood pressure and subsequently one or more organ systems to fail when blood supply to these organs is reduced. This may result in poor recovery and death. About a quarter of the people who suffer septic shock that is not rapidly reversed, will die.
When patients are admitted to Intensive Care with sepsis and/or septic shock they receive a number of therapies. These include fluids given through a drip, antibiotics, drugs to boost your blood pressure and other organ systems.
In addition to these therapies, steroids (hydrocortisone) are sometimes administered. Whether steroids are useful or not in the treatment of severe infections has been studied for more than 50 years. Previous research has suggested that the use of low dose steroid may have shortterm benefits in improving the circulation. However, there is no agreement amongst doctors around the world about whether treatment with or without low dose steroids improves the overall recovery and survival in patients with septic shock. This study would allow doctors to make informed decisions about whether the addition of low dose steroid therapy is better for patients with septic shock in intensive care.
The study will include 3800 intensive care patients who have septic shock. Each enrolled patient will be randomised to receive either Hydrocortisone 200mg or placebo daily for 7 days as a continuous intravenous infusion while in intensive care. The patient will be followed for 90 days. If the patient is discharged prior to 90 days a telephone call will be made for the followup information. At six months the patient will be contacted again for completion of a quality of life questionnaire.
详细描述
Primary Objective To evaluate the impact of intravenous hydrocortisone versus placebo on all cause mortality at 90 days in critically ill patients with septic shock. The hypothesis is that hydrocortisone, compared to placebo, reduces 90-day all-cause mortality in patients admitted to an ICU with septic shock. 'Shock' is defined as the need for vasopressors or inotropes to maintain a systolic blood pressure > 90 millimetres of mercury (mmHg), or mean arterial blood pressure > 60mmHg or a mean arterial pressure (MAP) target set by the treating clinician for maintaining perfusion. 'Septic shock' is shock that is secondary to sepsis
Secondary Objectives To assess the impact of intravenous hydrocortisone versus placebo on the recovery from, and the complications of, septic shock and the development of treatment related adverse reactions.
Study Design This study is a multi centre, randomised, blinded, placebo controlled trial comparing intravenous hydrocortisone with placebo in critically ill patients with septic shock.
Randomisation will be achieved via a secure interactive web based system using permuted block minimisation. Randomisation will be stratified by participating site and by operative or non-operative admission to the ICU.
The primary endpoint for this trial will be death from all causes at 90 days.
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
- •Aged 18 years or older
- •Documented site of infection, or strong suspicion of infection, with 2 of the 4 clinical signs of inflammation:
- •Core temperature > 38°C or < 35°C
- •Heart rate > 90 beats per minute
- •White cell count > 12 x 109/L or < 4 x 109/L or > 10% immature neutrophils
- •Respiratory rate > 20 breaths per minute, or PaCO2 < 32 mmHg, or mechanical ventilation.
- •Being treated with mechanical ventilation at the time of randomisation
- •Being treated with vasopressors or inotropes to maintain a systolic blood pressure > 90mmHg, or mean arterial blood pressure > 60mmHg, or a MAP target set by the treating clinician for maintaining perfusion
- •Administration of vasopressors or inotropes for = 4 hours and present at time of randomisation.
排除标准
- •Met all inclusion criteria more than 24 hours ago
- •Clinician expects to prescribe systemic corticosteroids for an indication other than septic shock (not including nebulised or inhaled corticosteroid)
- •Patients treated with etomidate
- •Patients receiving treatment with Amphotericin B for systemic fungal infections at time of randomisation
- •Patients with documented cerebral malaria at the time of randomisation
- •Patients with documented strongyloides infection at the time of randomisation
- •Death is deemed inevitable or imminent during this admission and either the attending physician, patient or surrogate legal decision maker is not committed to active treatment
- •Death from underlying disease is likely within 90 days
- •Patient has been previously enrolled in the ADRENAL study.
研究组 & 干预措施
Hydrocortisone
干预措施: Hydrocortisone (Drug)
Sterile air filled vial
干预措施: Sterile air filled vial (Drug)
结局指标
主要结局
All cause mortality at 90 days after randomisation
时间窗: 90 days after randomisation
次要结局
- Development of bacteraemia(2 and 14 days post randomisation)
- Duration of ICU stay(Up to 90 days after randomisation)
- Bleeding requiring blood transfusions received in the ICU(Up to 90 days after randomisation)
- All-cause mortality at 28 days and 6 months after randomisation(28 days and 6 months after randomisation)
- Duration of hospital stay(Up to 90 days after randomisation)
- Recurrence of shock(Up to90 days after randomisation)
- Frequency and duration of mechanical ventilation(Up to 90 days after randomisation)
- Quality of Life assessment at 6 months.(6 months.)
- Time to resolution of shock(MAP goal for >24 hours without vasopressors or inotropes. Up to 90 days after randomisation.)
- Duration of renal replacement therapy(Up to 90 days after randomisation)