Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis — CLOVERS  

Septic Shock Clinical Trial

Official title: Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis

Status Completed

Clinical Trial 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.

Clinical Trial 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 ;

Related Conditions & MeSH terms

• Sepsis
• Septic Shock

• NCT number: NCT03434028
• Study type: Interventional
• Source: Massachusetts General Hospital
• Status: Completed
• Phase: Phase 3
• Start date: March 7, 2018
• Completion date: August 24, 2022