Adjunctive Fludrocortisone in Septic Shock: a Multicenter, Double-blind, Randomized, Placebo-controlled Pilot Trial (AFLUDROS-1)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 32
- 试验地点
- 5
- 主要终点
- Number of Protocol deviations < 15%
研究概览
简要总结
Sepsis is a life-threatening condition caused by the body's dysregulated response to an infection. While corticosteroids are known to help stabilize blood pressure in septic shock, their ability to reduce mortality is still debated. Recent analyses suggest that combining fludrocortisone with hydrocortisone may be more effective at saving lives than hydrocortisone alone.
To test this hypothesis, a large, definitive international trial is needed. However, this research proposal is for a smaller pilot study (Phase II) involving 32 critically ill patients. The primary goal of this pilot is to determine the feasibility of conducting the subsequent large-scale trial that would compare hydrocortisone alone against the combination therapy and potentially change medical practice.
详细描述
Design: Pilot, multicenter, randomized, double-blind, placebo-controlled trial on use of adjunctive fludrocortisone in critically ill patients with septic shock.
Objective: Determine feasibility of conducting a large, international, multicenter, double-blind, randomized, placebo controlled efficacy trial of adjunctive fludrocortisone to improve septic shock mortality.
Setting: 6 intensive care units (ICU) in Hong Kong, Australia and Singapore. Participants: 32 adult participants with suspected or confirmed septic shock within 24 hours of onset of shock and mechanical ventilation. Exclusion criteria are pregnancy, limitation of therapy, prescribed fludrocortisone for other medical condition, fludrocortisone cannot be administered within 24 hours of shock onset.
Interventions: Enteral 100 mcg fludrocortisone daily or placebo for up to 7 days or until death or discharge from ICU, whichever comes first.
Main outcome measures: Primary outcome is fulfillment of all pre-specified endpoints of feasibility criteria: protocol deviation <15%, lost of concealment <10%, drop out rate <10% and missing data <10%. Secondary outcomes include monthly recruitment rate, time to resolution of shock, 28-day mortality, days alive and free from organ support, severe electrolyte abnormality.
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
- •suspected or confirmed adult sepsis as defined by ≥ 2 increase in Sequential Organ Failure Assessment (SOFA) score due to infection
- •≥0.25 μg/kg/min of noradrenaline infusion or vasoactive-inotropic score (VIS) ≥25 to maintain mean arterial pressure (MAP) ≥65 mmHg for at least 1 hour
- •onset of septic shock within 24 hours
- •shock due to infection with no other proven or apparent cause
- •hypoperfusion defined as arterial or venous lactate concentration >2.0 mmol/L
- •mechanical ventilation
排除标准
- •fludrocortisone cannot be administered within 24 hours of onset of septic shock
- •death is deemed imminent or inevitable by treating clinicians
- •limitation of therapy
- •an underlying disease process with a life expectancy of less than 90 days
- •pregnancy (confirmed or suspected)
- •receiving immunomodulatory agents including hydrocortisone > 300mg/day
- •enteral medication cannot be administered
- •prescribed fludrocortisone for other medical condition
- •contraindication to hydrocortisone or fludrocortisone
研究组 & 干预措施
Fludrocortisone
干预措施: Fludrocortisone 100 mcg daily (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Protocol deviations < 15%
时间窗: End of study approximately 20 months
Defined as \<15% of recruited subjects that had at least one protocol deviation during the duration of intervention
Number of Lost of concealment < 10%
时间窗: End of study approximately 20 months
Defined as \<10% of recruited subjects that lost blinding of allocations to either the patient, clinical or trial statistician
Number of Drop out < 10%
时间窗: End of study approximately 20 months
Defined as \<10% of recruited subjects who drop out of the study after recruitment
Number of Missing data < 10%
时间窗: End of study approximately 20 months
Defined as \<10% of data with missing values for each data category including lost to follow up
次要结局
- Number of Monthly Recruitment(End of study approximately 20 months)
- Time to resolution of shock(Until patient discharge from ICU)
- 28-day mortality(First 28 days after enrollment)
- Days alive and vasopressor-free until day 28(First 28 days after enrollment)
- Days alive and ventilator-free until day 28(First 28 days after enrollment)
- Days alive and dialysis-free until day 28(First 28 days after enrollment)
- Days alive and free from organ support(First 28 days after enrollment)
- Number of new onset infections(First 28 days after enrollment)
- Severe electrolyte abnormality(First 7 days after enrollment)
研究者
Lowell Ling
Associate Professor
Chinese University of Hong Kong