Phase 3
N=1,563
Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis
Septic Shock
Bottom Line
View on ClinicalTrials.gov: NCT03434028 ↗Enrolled (actual)
1,563
Serious AEs
2.4%
Results posted
Jul 2023
Primary outcome: Primary: Death Before Discharge Home by Day 90 — 14; 14.9 percentage of participants — p=0.61
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Early Vasopressors (Drug); Early Fluids (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Massachusetts General Hospital
- Primary completion
- May 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Death Before Discharge Home by Day 90 |
14; 14.9 | 0.61 |
| SECONDARY Organ Support Free Days |
24; 23.6 | — |
| SECONDARY Ventilator Free Days (VFD) |
23.4; 22.8 | — |
| SECONDARY Renal Replacement Free Days |
24.1; 23.9 | — |
| SECONDARY Vasopressor Free Days |
22; 21.6 | — |
| SECONDARY ICU Free Days |
22.8; 22.7 | — |
| SECONDARY Hospital Free Days to Discharge Home |
16.2; 15.4 | — |
| SECONDARY New Intubation With Invasive Mechanical Ventilation by 28 Days |
77; 87 | — |
| SECONDARY Initiation of Renal Replacement Therapy |
24; 24 | — |
| SECONDARY Kidney Disease: Change in Creatinine-based Global Outcomes (KIDGO) Score Between Baseline and 72 Hours |
0.35; 0.34 | — |
| SECONDARY Change in SOFA (Sepsis Related Organ Failure Assessment) Score |
-0.7; -0.8 | — |
| SECONDARY Development of ARDS |
19; 20 | — |
| SECONDARY New Onset Atrial or Ventricular Arrhythmia |
59; 67 | — |
| SECONDARY Death From Any Cause at Any Location by Day 90 |
172; 169 | — |
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
Data sourced from ClinicalTrials.gov (NCT03434028). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.