Sepsis
Conditions
Keywords
Sepsis, Hypotension, IV fluid therapy, Fluid resuscitation, Emergency Department, Crystalloids
Brief summary
This is an investigator-initiated, multicenter, randomized, parallel-group, open-labeled, feasibility trial investigating volumes of fluid within 24 hours in 124 patients with sepsis allocated to two different IV fluid regimens enrolled at three emergency departments in Central Region Denmark. The primary outcome is total intravenous, crystalloid fluid volume within 24 hours and key secondary outcomes include protocol violations, total fluids (intravenous and oral) within 24 hours, SAEs/SUSARs, and inhospital-, 30- and 90-day mortality.
Detailed description
BACKGROUND: Sepsis is common in emergency department (ED) patients. Traditionally, intravenous (IV) fluids are used to optimise the circulation, and the use of higher volumes is recommended by international guidelines, but there are no recommendations for sepsis without hypotension or shock. Studies in septic shock seem to favour fluid restriction. Whether this is true in sepsis without hypotension/shock is unknown. OBJECTIVES: The aim of the REFACED Sepsis trial is to test if an IV fluid restrictive protocol in ED patients with sepsis is feasible, i.e., if the protocol decreases the IV fluid volumes administered. DESIGN: REFACED Sepsis is a multicenter, randomized, parallel-group, open-labeled, feasibility trial POPULATION: ED patients with sepsis expected to be admitted for ≥ 24 hours EXPERIMENTAL INTERVENTION: In the IV fluid restriction group no IV fluids should be given unless one of the below mentioned occurs; A fluid bolus of 250 ml isotonic crystalloid may be given within 15 minutes if one of the following occurs (hypoperfusion criteria): * Lactate concentration ≥ 4 mmol/l (arterial or venous blood gas/blood sample) * Hypotension (systolic BP \< 90 mmHg) * Mottling beyond edge of kneecap (i.e., Mottling score \>2)53 * Severe oliguria, i.e., diuresis \< 0.1 ml/kg/h, during the first 4 hours of admission All patients will be ensured min. 1 L of oral/intravenous fluids in 24 hours and electrolytes can be corrected. CONTROL INTERVENTION: In the usual care group there will be no upper limit for the use of IV fluids. OUTCOMES: The primary outcome is 24-hour intravenous crystalloid fluid administration. Key secondary outcomes are: Feasibility measures: Number of patients with major protocol violations, Number of patients screened vs included, Time from admission to inclusion, Number of patients lost to follow up in terms of 24-hour fluids, Accumulated serious adverse reactions and events (SAEs + Suspected Unexpected Serious Adverse Reaction (SUSARs)) within 48 hours in-hospital, Total fluids (oral and intravenous) at 24 hours, TRIAL-SIZE: 124 patients will be randomized to restrictive fluid administration or usual care within 24 hours of randomization
Interventions
Types of fluids in both intervention groups: * Fluids used for electrolyte disturbances: Fluids should be chosen to substitute the specific deficiency * Fluids given to substitute overt loss: Isotonic crystalloids are to be used. If large amounts of ascites are tapped, then human albumin may be used. * Blood products are only to be used on specific indications including severe bleeding, severe anaemia and prophylactic in case of severe coagulopathy.
Sponsors
University of Aarhus
Aarhus University Hospital
Viborg Regional Hospital
Randers Regional Hospital
Marie Kristine Jessen, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All of the below must be fulfilled: 1. Unplanned emergency department admission 2. Age ≥ 18 years 3. Sepsis defined as 1. suspected infection by the treating clinician AND 2. blood cultures drawn AND 3. IV antibiotics administered or planned AND 4. An infection related increase of SOFA\*-score ≥ 2 from baseline 4. Expected hospital stay \> 24 hours as deemed by treating clinician * Sequential Organ Failure Assessment (SOFA) Score Further more the patient must fulfill criteria for enrollment in an acute study according to Danish law
Exclusion criteria
We will exclude patients fulfilling any of following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour crystalloid iv. fluids | 24 hours from randomization | total amount of all administered intravenous, crystalloid fluids within 24 hours of randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Screened-vs.-randomized-ratio | Through study completion, an average of 1 year | Feasibility measure: Number of patients screened vs included |
| Time to inclusion | Through study completion, an average of 1 year | Feasibility measure: Time from admission to inclusion/randomization (hours) |
| Lost-to-follow-up-rate | 24 hours from randomization | Feasibility measure: Number of patients lost to follow up in terms of 24-hour fluids |
| Protocol violations | 24 hours from randomization | Feasibility measure: Number of patients with major protocol violations |
| Total 24-hour fluids | 24 hours from randomization | Total fluids (oral and intravenous) at 24 hours |
| Mortality | Total of 90-days | In-hospital, 30- and 90-days mortality |
| Accumulated serious adverse reactions (SARs + SUSARs) | 7 days from randomization | Feasibility measure: Accumulated serious adverse reactions and events (SAEs + SARs+ SUSARs) within 7 days in-hospital |
Countries
Denmark
Outcome results
None listed