Hydrocortisone and Fludrocortisone for Critical Illness-related Corticosteroid Insufficiency
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,092
- 试验地点
- 1
- 主要终点
- number of ventilator- and vasopressor-free days
研究概览
简要总结
The study aims at assessing the efficacy and the safety of hydrocortisone combined with fludrocortisone compared to placebo in ICU adults with critical illness related corticosteroid insufficiency.
详细描述
The hypothalamic-pituitary-adrenal axis together with the noradrenergic/vasopressinergic system are the main systems of host response to stress. In 2008 the scientific community described a syndrome called critical illness related corticosteroids insufficiency (CIRCI) in which body homeostasis is lost owing to insufficient cortisol production or bioactivity in tissues. Recent updates of international guidelines have spelled out the pathophysiology, diagnosis and management of CIRCI. The prevalence of CIRCI varies according to case mix and severity of illness. The combination of hydrocortisone and fludrocortisone improved outcomes in septic shock, a condition often complicated with CIRCI. However, there is insufficient evidence on the efficacy of corticosteroids in patients with CIRCI and without septic shock. The hypothesis of the study is that the hydrocortisone-fludrocortisone association will improve ventilation and vasopressor free survival in ICU patients with Critical illness related Corticosteroid Insufficiency.
Patients with a SOFA score ≥ 4 will be screened for CIRCI. Patients suffering from CIRCI will be randomized to receive hydrocortisone and fludrocortisone or their placebo. Patients without CIRCI will receive standard of care and will be followed up during 90 days (cohort-observational study).
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
- •Adult (≥ 18 years);
- •Hospitalized in an intensive care unit;
- •SOFA score ≥ 4, for at least 6 consecutive hours;
- •Informed written consent from patient or from legally authorized next of kin, or emergency deferred consent;
- •Affiliation to a social security system or to a universal health coverage (Couverture Maladie Universelle, CMU).
排除标准
- •Any suspected or proven acute adrenal insufficiency (As defined in international guidelines; basal cortisol < 5 μg/dL or peak (60) cortisol <18 μg/dL)
- •Expected death or withdrawal of life-sustaining treatments within 48 hours
- •Known chronic adrenal insufficiency
- •Concomitant treatment that inhibits cortisol production
- •Septic shock (Singer Jama 2016)
- •Active tuberculosis or fungal infection
- •Active viral hepatitis or active infection with herpes viruses
- •Hypersensitivity or contraindication to hydrocortisone, fludrocortisone or Synacthène® or any of their excipients ( SmPC)
- •Patient needing either anti-inflammatory corticosteroids or substitutive hydrocortisone for any reason (Such as those suffering from COVID-19 pneumonia requiring oxygen therapy).
- •Current treatment by more than 15 mg/d of prednisone (or equivalent) for more than 30 days
- •Diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome
- •Pregnant or breastfeeding woman
- •Moribund patient
- •Previously enrolled in this study
- •Participation to another interventional study that focuses on CIRCI and/or corticoid drugs and/or that addresses a similar primary endpoint as Hornbill ( ventilator- and vasopressor-free survival )
- •Patient under guardianship or tutorship
- •Note: Included patients for whom acute adrenal insufficiency would be detected in the Synacthen ® test performed as part of the research for the diagnosis of CIRCI will not be randomized since they should be treated by corticosteroids.
研究组 & 干预措施
Active
For CIRCI patients: hydrocortisone + fludrocortisone therapy.
干预措施: Investigational products administration (Drug)
Placebo
For CIRCI patients: hydrocortisone placebo + fludrocortisone placebo
干预措施: Placebo administration (Drug)
结局指标
主要结局
number of ventilator- and vasopressor-free days
时间窗: at day 30
number of ventilator- and vasopressor-free days within 30 days (deaths assigned zero days) after randomisation.
次要结局
- Safety endpoints - hospital-acquired infections proportion(daily up to 30 days)
- Safety endpoints - hyperglycemia(daily up to 30 days)
- Mortality rates(at day 30, 90 and 180)
- Safety endpoints - corticosteroids administration requiring(daily up to 30 days)
- Rate of ventilation(at day 30)
- Withhold and/or withdraw proportion(up to 3 months)
- duration of hospitalization of stay(daily up to 30 days)
- response to glucocorticoids(up to 3 months)
- Number of days alive free of mechanical ventilation(at day 30)
- Number of days alive with SOFA < 4(daily un to 30 days)
- Safety endpoints - hypernatremia(daily up to 30 days)
- Safety endpoints - Gastroduodenal bleeding(daily up to 30 days)
- Change in quality of life(up to Day 30 and 90)
- Number of days alive without vasopressors(at day 30)
- ICU duration(up to 3 months)
- Rate of re-admission to the ICU(daily up to 30 days)
- Safety endpoints - serious adverse events associated with corticosteroids(daily up to 30 days)
- Rate of ventilation and vasopressors free survival at day 90(at day 90)
- Renal replacement therapy (RRT)-free days(up to day 30)
- Vasopressors free days(at day 30)