Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients

Sepsis Clinical Trial

— REFACED Sepsis  

Official title:

Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients - a Multicenter, Randomized Clinical Feasibility Trial (REFACED Sepsis)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05076435
• Other study ID #: RECEM0001
• Secondary ID: 2021-000224-351-
• Status: Completed
• Phase: Phase 2
• Start date: November 3, 2021
• Est. completion date: March 19, 2022

Study information

• Verified date: March 2022
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: March 19, 2022
• Est. primary completion date: December 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 exclusion criteria:

1. = 500 ml of fluids given prior to randomization

2. Invasively ventilated or vasopressors initiated at the time of screening

3. Known or suspected severe bleeding judged by the treating clinician

4. Known or suspected pregnancy (women aged <45 years will have a pregnancy test performed before enrollment)

5. Prior enrollment in the trial

6. Patients, who the clinician expect not to survive the next 24-hours

Related Conditions & MeSH terms

• Emergencies
• Sepsis
• Toxemia

Intervention

Drug:
• Isotonic crystalloids
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.

Locations

Country	Name	City	State
Denmark	Department of Emergency Medicine, Aarhus University Hospital	Aarhus	Central Denmark Region
Denmark	Department of Emergency Medicine, Regional Hospital Randers	Randers	Central Denmark Region
Denmark	Department of Emergency Medicine, Regional Hospital Viborg	Viborg	Central Denmark Region

Sponsors (5)

Lead Sponsor	Collaborator
Marie Kristine Jessen, MD	Aarhus University Hospital, Randers Regional Hospital, University of Aarhus, Viborg Regional Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	24-hour crystalloid iv. fluids	total amount of all administered intravenous, crystalloid fluids within 24 hours of randomization	24 hours from randomization
Secondary	Protocol violations	Feasibility measure: Number of patients with major protocol violations	24 hours from randomization
Secondary	Screened-vs.-randomized-ratio	Feasibility measure: Number of patients screened vs included	Through study completion, an average of 1 year
Secondary	Time to inclusion	Feasibility measure: Time from admission to inclusion/randomization (hours)	Through study completion, an average of 1 year
Secondary	Lost-to-follow-up-rate	Feasibility measure: Number of patients lost to follow up in terms of 24-hour fluids	24 hours from randomization
Secondary	Accumulated serious adverse reactions (SARs + SUSARs)	Feasibility measure: Accumulated serious adverse reactions and events (SAEs + SARs+ SUSARs) within 7 days in-hospital	7 days from randomization
Secondary	Total 24-hour fluids	Total fluids (oral and intravenous) at 24 hours	24 hours from randomization
Secondary	Mortality	In-hospital, 30- and 90-days mortality	Total of 90-days