Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis
Purpose
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.
Condition
- Septic Shock
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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).
Exclusion Criteria
- 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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Other Restrictive Fluids |
The general approach will be to use vasopressors to treat hypotension as opposed to intravenous fluids. Maintenance fluids should not be used. |
|
Other Liberal Fluids |
The general approach is to use fluid boluses to treat hypotension. |
|
More Details
- Status
- Completed
- Sponsor
- Massachusetts General Hospital
Study Contact
Detailed Description
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. 1. 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. 2. 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 3. 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