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

NCT05076435 | Completed Phase 2

• 3 other identifiers: RECEM00012021-000224-351-10-72-163-21
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 3

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.

Conditions

Sepsis

Keywords

Sepsis; Hypotension; IV fluid therapy; Fluid resuscitation; Emergency Department; Crystalloids

Outcome Measures

Primary Outcomes (1)

• 24-hour crystalloid iv. fluids

  total amount of all administered intravenous, crystalloid fluids within 24 hours of randomization

  24 hours from randomization

Secondary Outcomes (7)

• Protocol violations

  24 hours from randomization

• Screened-vs.-randomized-ratio

  Through study completion, an average of 1 year

• Time to inclusion

  Through study completion, an average of 1 year

• Lost-to-follow-up-rate

  24 hours from randomization

• Accumulated serious adverse reactions (SARs + SUSARs)

  7 days from randomization

Study Arms (2)

Restrictive fluid administration

EXPERIMENTAL

No IV fluids unless one of the extenuating circumstances occur; 1. In case of severe hypoperfusion or severe circulatory impairment defined by either: 1) Lactate≥4 mmol/L, 2) Hypotension (systolic BP \< 90 mmHg), 3) Mottling beyond the kneecap (mottling score \>2) OR 4) Urinary output\<0.1 mL/kg bodyweight/h (only in the first 4hrs after randomization) then a bolus of 250 ml of IV crystalloid solution may be given followed by re-evaluation 2. In case of overt fluid losses (e.g. vomiting, large aspirates,) IV fluid may be given to correct for the loss, but not above the volume lost. 3. In case the oral/enteral route for water or electrolyte solutions is contraindicated or has failed, IV fluids may be given to: Correct dehydration or electrolyte deficiencies Ensure a total fluid input of 1 L in 24hrs 4. IV fluids may be given as carrier for medication, but with lowest possible volume

Drug: Isotonic crystalloids

Usual care (standard care)

ACTIVE COMPARATOR

There will be no upper limit for the use of either IV or oral/enteral fluids 1. IV fluids should be given in the case of hypoperfusion or circulatory impairment and should be continued as long as hemodynamic variables improve including static or dynamic variable(s) as chosen by the clinicians. These criteria are based on the Surviving Sepsis Campaign guideline. 2. IV fluids should be given as maintenance if the ICU has a protocol recommending maintenance fluid 3. IV fluids should be given to substitute expected or observed loss, dehydration or electrolyte derangements

Drug: Isotonic crystalloids

Interventions

Isotonic crystalloids DRUG

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.

Restrictive fluid administration; Usual care (standard care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unplanned emergency department admission
• Age ≥ 18 years
• Sepsis defined as
• suspected infection by the treating clinician AND
• blood cultures drawn AND
• IV antibiotics administered or planned AND
• An infection related increase of SOFA\*-score ≥ 2 from baseline
• 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

You may not qualify if:

• ≥ 500 ml of fluids given prior to randomization
• Invasively ventilated or vasopressors initiated at the time of screening
• Known or suspected severe bleeding judged by the treating clinician
• Known or suspected pregnancy (women aged \<45 years will have a pregnancy test performed before enrollment)
• Prior enrollment in the trial
• Patients, who the clinician expect not to survive the next 24-hours

Sponsors & Collaborators

• Marie Kristine Jessen, MD: lead
• University of Aarhus: collaborator
• Aarhus University Hospital: collaborator
• Viborg Regional Hospital: collaborator
• Randers Regional Hospital: collaborator

Study Sites (3)

Department of Emergency Medicine, Aarhus University Hospital

Aarhus, Central Jutland, 8200, Denmark

Location

Department of Emergency Medicine, Regional Hospital Randers

Randers, Central Jutland, 8930, Denmark

Location

Department of Emergency Medicine, Regional Hospital Viborg

Viborg, Central Jutland, 8800, Denmark

Location

Related Publications (2)

• Jessen MK, Andersen LW, Thomsen MH, Kristensen P, Hayeri W, Hassel RE, Messerschmidt TG, Solling CG, Perner A, Petersen JAK, Kirkegaard H. Restrictive fluids versus standard care in adults with sepsis in the emergency department (REFACED): A multicenter, randomized feasibility trial. Acad Emerg Med. 2022 Oct;29(10):1172-1184. doi: 10.1111/acem.14546. Epub 2022 Aug 5.

  PMID: 35652491 DERIVED

• Jessen MK, Andersen LW, Thomsen MH, Kristensen P, Hayeri W, Hassel RE, Perner A, Petersen JAK, Kirkegaard H. Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients (REFACED Sepsis)-protocol for a multicenter, randomized, clinical, proof-of-concept trial. Pilot Feasibility Stud. 2022 Mar 29;8(1):75. doi: 10.1186/s40814-022-01034-y.

  PMID: 35351214 DERIVED

MeSH Terms

Conditions

Sepsis; Hypotension; Emergencies

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Disease Attributes

Study Officials

• Marie K Jessen, MD

  Research Center for Emergency Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 11, 2021
• First Posted: October 13, 2021
• Study Start: November 3, 2021
• Primary Completion: December 19, 2021
• Study Completion: March 19, 2022
• Last Updated: March 25, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (3)