Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis
Condition: Septic Shock
MeSH terms: Sepsis
Intervention: Early Vasopressors; Early Fluids
Intervention description: 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.; Additional 2 liter intravenous fluid 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. Any type of isotonic crystalloid (normal saline, ringers lactate, balanced solution such as plasmalyte) is permitted.
Intervention MeSH terms: Norepinephrine; Vasoconstrictor Agents
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1563.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Fluid management; Sepsis-induced hypotension; vasopressors

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.
    

Eligibility criteria:

        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