Steroid Use in Pediatric Fluid and Vasoactive Infusion Dependent Shock - Pilot Study (STRIPES)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 7
- 主要终点
- Patient Accrual Rate Over One Year (% of Target Sample Size Achieved)
研究概览
简要总结
Approximately 20,000 children per year in North America present to the hospital with severe shock. Children who develop this condition have very low blood pressures and as a result may suffer damage to their internal organs and may even die. Some children with this condition may significantly benefit from the use of steroids but steroids in such patients may also have potential side effects. Therefore it is important to study the use of steroids carefully in these children. The STRIPES research program will examine the effectiveness and safety of steroids in children. Before conducting a large, randomized controlled trial (RCT), a pilot study (STRIPES Pilot Study) will be conducted in multiple sites across Canada. The STRIPES Pilot Study will allow testing of the STRIPES study protocol in a smaller group of patients.
详细描述
This study is a multi-centre pilot RCT to determine the feasibility of doing a full trial on the effect of steroids versus placebo in children with fluid and vasoactive infusion dependent shock. The principal investigator and colleagues recently published two articles on this topic which were selected as the Feature Article and Feature Review in the June edition of Pediatric Critical Care Medicine. Both of these publications strongly support the interest in this area and the accompanying editorial strongly supported the need for a well-designed RCT.
RATIONALE: Approximately 20,000 children per year present to emergency departments, pediatric wards and intensive care units in North America with fluid and vasoactive infusion dependent shock. This severe type of shock results in significant morbidity and carries a 2-10% mortality rate depending on the setting in which it occurs. This form of shock is thought to arise from dysfunction of the hypothalamic-pituitary-adrenal axis through a variety of mechanisms and has been referred to as relative adrenal insufficiency or critical illness related adrenal insufficiency. Many clinicians believe that corticosteroids improve outcomes in such patients and therefore use them when confronted with a critically ill child with fluid and vasoactive infusion dependent shock. However, the effectiveness and safety of steroid replacement therapy in pediatric shock remain to be demonstrated.
OBJECTIVES - PILOT STUDY: Before embarking on a multi-centre definitive trial to address the questions listed above, the STRIPES Pilot Study has 3 specific feasibility objectives: 1) To estimate the rate of patient recruitment and understand barriers to recruitment; 2) To assess adherence to our specific treatment protocol; and 3) To document the frequency of and understand the reasons for open label steroid use.
OBJECTIVES - FULL RCT: Following successful completion of the STRIPES Pilot Study, the next phase will be a large, multi centre RCT to answer the following questions: 1) What is the effect of hydrocortisone versus placebo on the time to discontinuation of vasoactive agents among pediatric patients with fluid and vasoactive infusion dependent shock?; and 2) In patients with fluid and vasoactive infusion dependent shock, what is the effect of hydrocortisone versus placebo on i) pediatric intensive care unit (PICU) mortality; ii) duration of mechanical ventilation; iii) new onset of organ dysfunction; iv) PICU length of stay; and v) incidence of adverse events?
RESEARCH PLAN: The STRIPES Pilot Study is designed as a pragmatic, multi-centre, double blind, RCT of intravenous hydrocortisone versus intravenous placebo in fluid and vasoactive infusion dependent shock. This study aims to enroll 72 patients from 7 pediatric centres across Canada over a one year period. Patients will be recruited from the Emergency Department and the PICU within 6 hours of being stared on a vasoactive agent. Research ethics board approval will be obtained from all participating centres and application for deferred consent will be made at 5 sites. Health Canada approval is not required as hydrocortisone is approved for use in children at the doses and for the indication for which it is being used in this 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
- 1 Day 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children newborn to 17 years
- •On any dose of any vasoactive infusion for between 1 to 6 hours
排除标准
- •Patients who have known or suspected hypothalamic, pituitary or adrenal disease
- •Patients who are currently receiving steroids for the treatment of shock/suspected shock prior to randomization
- •Patients who are expected to have treatment withdrawn
- •Patients who are premature infants (<38 weeks corrected gestational age)
- •Patients who are pregnant
- •Patients post cardiac surgery
- •Patient who received their first dose of vasoactive infusion >24 hours after PICU admission
- •Patient who is no longer on vasoactive infusion at the time of study enrollment, and/or is expected to no longer be on vasoactive infusion at the time the first dose of study drug will be administered
- •Patients for whom primary cardiogenic shock is strongly suspected
- •Patients for whom spinal shock is strongly suspected
- •Patients for whom hemorrhagic or hypovolemic shock is strongly suspected
- •Patients who were previously enrolled in the STRIPES study
- •Patients who receive a vasoactive agent for reasons not related to shock
- •Physician refusal
研究组 & 干预措施
Hydrocortisone
Patients randomized to the hydrocortisone arm will receive a 2 mg/kg hydrocortisone IV bolus on enrolment followed by 1 mg/kg of hydrocortisone IV q6h until the patient has not had an escalation in therapy for at least 12 hours. If the patient meets these criteria their hydrocortisone will be weaned to 1 mg/kg every 8 hours which will be continued until they are off all vasoactive infusions for 12 hours. If following the initial hydrocortisone wean, the patient requires fluid boluses and/or an increase in their vasoactive infusion(s), their hydrocortisone will be increased back to 1 mg/kg of hydrocortisone IV q6h until they meet stability criteria again. Duration of treatment will range from a minimum of 20 hours to a maximum of 7 days of study drug.
干预措施: Hydrocortisone (Drug)
Placebo
Patients randomized to the placebo arm will receive a placebo solution consisting of normal saline equivalent in volume to the appropriate dose of hydrocortisone. Hydrocortisone and placebo will be identical in appearance, volume and smell as hydrocortisone is made up in normal saline and dissolves completely with no visible precipitate. The dosing regimen will be identical to the hydrocortisone arm.
干预措施: Placebo (Other)
结局指标
主要结局
Patient Accrual Rate Over One Year (% of Target Sample Size Achieved)
时间窗: 1 year
The total number of participants recruited over the recruitment period to both arms (this was a feasibility outcome that was analyzed for the full cohort and, as stated a priori in the study protocol was not compared between study arms). Our goal is to recruit 72 patients over one year . However, we will consider patient accrual rate to be adequate if we recruit 60 patients from seven sites within this time period.
次要结局
- 1a. Time to Administration of the First Dose of Study Drug(8 hours from starting vasoactive medication)
- Number of Patients Started on Open Label Steroids by the Treating Physician(7 days)
- 1b. Weaning of Study Drug to q8h When Patient is Hemodynamically Stable(7 days)
- Time to Discontinuation of Vasoactive Infusions(Daily during hospital admission (up to 28 days))
- 1c. Discontinuation of Study Drug When Off All Vasoactive Medications(7 days)
- Number of Participants With Incidence of Adverse Events and Mortality in the Full Cohort(Daily during hospital admission (up to 28 days))
- Percentage of Patients for Whom Blood Samples Are Sent, and Successfully Received and Analyzed in Their Respective Labs(End of the study recruitment phase (up to 1.5 years))
研究者
Kusum Menon
Senior Investigator, CHEO Research Institute; Associate Professor, University of Ottawa; Physician, Division of Critical Care
Children's Hospital of Eastern Ontario