Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA UCSF
Dates
study started
estimated completion

Description

Summary

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.

Official Title

Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis

Details

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

Keywords

Septic Shock Fluid management Sepsis-induced hypotension vasopressors Sepsis Vasoconstrictor Agents Early Vasopressors Early Fluids Restrictive Fluids Liberal Fluids

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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).

You CAN'T join if...

  • 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

Locations

  • UCSF Fresno accepting new patients
    Fresno California 93701 United States
  • Ronald Reagan UCLA accepting new patients
    Los Angeles California 90095 United States
  • UCSF San Francisco accepting new patients
    San Francisco California 94143 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Massachusetts General Hospital
ID
NCT03434028
Phase
Phase 3
Study Type
Interventional
Last Updated