Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,563
- 试验地点
- 49
- 主要终点
- Death Before Discharge Home by Day 90
研究概览
简要总结
Multicenter, prospective, phase 3 randomized non-blinded interventional trial of fluid treatment strategies in the first 24 hours for patients with sepsis-induced hypotension. The aim of the study is to determine the impact of a restrictive fluids strategy (vasopressors first followed by rescue fluids) as compared to a liberal fluid strategy (fluids first followed by rescue vasopressors) on 90-day in-hospital mortality in patients with sepsis-induced hypotension.
详细描述
Primary Hypothesis: Restrictive (vs liberal) fluid treatment strategy during the first 24 hours of resuscitation for sepsis-induced hypotension will reduce 90-day in-hospital mortality.
- We will emphasize early screening and protocol initiation, and enroll a maximum of 2320 patients with suspected sepsis-induced hypotension.
- All patients will receive at least 1 liter of fluids prior to meeting study inclusion criteria (and no more than 3 liters prior to randomization).
- Patients will be enrolled within 4 hours of meeting study inclusion criteria
- Any type of isotonic crystalloid (normal saline, ringers lactate, or a balanced solution such as plasmalyte) is permitted.
- Restrictive Fluids (Early Vasopressors) Group
- Norepinephrine will be used as preferred vasopressor and titrated to achieve mean arterial pressure (MAP) between 65 mmHg and 75 mmHg
- "Rescue fluids" may be administered as 500ml boluses if predefined rescue criteria are met
- Liberal Fluids (Fluids First)
- 2 liter infusion upon enrollment (may forego second liter if MAP/SBP and heart rate are normalized and clinical assessment if patient is fluid replete after the first liter).
- Administer 500ml fluid boluses for fluid triggers until 5 liters administered or development of clinical signs of acute volume overload develop
- "Rescue vasopressors" may be administered after 5 liters of fluid, for development of acute volume overload, or if other predefined rescue criteria are met
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
- None
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
- •Age ≥ 18 years
- •A suspected or confirmed infection (broadly defined by administration or planned administration of antibiotics)
- •Sepsis-induced hypotension defined as systolic blood pressure < 100 mmHg or MAP < 65 mmHg after a minimum of at least 1 liter of fluid (*Fluids inclusive of pre-hospital fluids; blood pressure must be below any known or reported pre-morbid baseline).
排除标准
- •More than 4 hours elapsed since meeting inclusion criteria or 24 hours elapsed since admission to the hospital
- •Patient already received 3 liters of intravenous fluid (includes prehospital volumes)
- •Unable to obtain informed consent
- •Known pregnancy
- •Hypotension suspected to be due to non-sepsis cause (e.g. hemorrhagic shock)
- •Blood pressure is at known or reported baseline level
- •Severe Volume Depletion from an acute condition other than sepsis. In the judgment of the treating physician, the patient has an acute condition other than sepsis causing (or indicative) of *severe volume depletion; Examples include: Diabetic ketoacidosis, high volume vomiting or diarrhea, hyperosmolar hyperglycemic state, and nonexertional hyperthermia (heat stroke); severe is defined by the need for substantial intravenous fluid administration as part of routine clinical care
- •Pulmonary edema or clinical signs of new fluid overload (e.g. bilateral crackles, new oxygen requirement, new peripheral edema, fluid overload on chest x-ray)
- •Treating physician unwilling to give additional fluids as directed by the liberal protocol
- •Treating physician unwilling to use vasopressors as directed by the restrictive protocol.
- •Current or imminent decision to withhold most/all life-sustaining treatment; this does not exclude those patients committed to full support except cardiopulmonary resuscitation
- •Immediate surgical intervention planned such that study procedures could not be followed
- •Prior enrollment in this study
研究组 & 干预措施
Restrictive Fluids
The general approach will be to use vasopressors to treat hypotension as opposed to intravenous fluids. Maintenance fluids should not be used.
干预措施: Early Vasopressors (Drug)
Liberal Fluids
The general approach is to use fluid boluses to treat hypotension.
干预措施: Early Fluids (Other)
结局指标
主要结局
Death Before Discharge Home by Day 90
时间窗: From randomization to discharge home up to and including day 90.
The primary outcome was death from any cause before discharge home by day 90. Point estimates were from Kaplan-Meier curves. There were 109 deaths and 5 patients with censored data the restrictive fluid group and 116 deaths and 4 patients with censored data in the liberal group. We defined home as the same setting or a setting similar to the one where the patient resided before becoming ill. Thus, if a patient originated from a private residence and was discharged from the hospital to a rehabilitation setting, we assessed for vital status until return to the private residence.Vital status was determined using any of the following methods: medical record review, phone calls to patient, proxy or healthcare facility, review of obituaries, or information from the Centers for Disease Control and Prevention's National Death Index (NDI).
次要结局
- Vasopressor Free Days(From study day 2 through day 28)
- New Intubation With Invasive Mechanical Ventilation by 28 Days(28 days after randomization)
- Organ Support Free Days(28 days after randomization)
- Renal Replacement Free Days(28 days after randomization)
- ICU Free Days(28 days after randomization)
- Kidney Disease: Change in Creatinine-based Global Outcomes (KIDGO) Score Between Baseline and 72 Hours(72 hours after randomization)
- Hospital Free Days to Discharge Home(28 days after randomization)
- Death From Any Cause at Any Location by Day 90(From randomization to and including day 90)
- Development of ARDS(7 days after randomization)
- Ventilator Free Days (VFD)(28 days after randomization)
- Initiation of Renal Replacement Therapy(28 days after randomization)
- New Onset Atrial or Ventricular Arrhythmia(28 days after randomization)
- Change in SOFA (Sepsis Related Organ Failure Assessment) Score(72 hours after randomization)
研究者
Boyd Taylor Thompson
PETAL CCC Prinicipal Investigator
Massachusetts General Hospital