Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis
a study on Septic Shock
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.
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 (See Protocol Schema Appendix A)
- 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) Group (See Protocol Schema Appendix A)
- Additional 2 liter intravenous fluid bolus upon enrollment
- 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
Septic Shock Fluid management Sepsis-induced hypotension vasopressors Sepsis Shock, Septic Vasoconstrictor Agents
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
- UCSF Fresno not yet accepting patients
Fresno, California, 93701, United States
- UCSF San Francisco accepting new patients
San Francisco, California, 94143, United States
- Stanford University Hospital not yet accepting patients
Stanford, California, 94305, United States
- Ronald Reagan UCLA not yet accepting patients
Los Angeles, California, 90095, United States
- accepting new patients
- Start Date
- Completion Date
- Massachusetts General Hospital
- Phase 3
- Study Type
- Last Updated
- March 13, 2018
Please contact me about this study
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If you do not hear from the study team, please call 888-689-8273 and tell them you’re interested in study number NCT03434028.