Denna sida har översatts automatiskt och översättningens korrekthet kan inte garanteras. Vänligen se engelsk version för en källtext.

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

24 mars 2022 uppdaterad av: Marie Kristine Jessen, MD

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

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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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

Studietyp

Interventionell

Inskrivning (Faktisk)

124

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Danmark
    • Central Denmark Region
      • Aarhus, Central Denmark Region, Danmark, 8200
        • Department of Emergency Medicine, Aarhus University Hospital
      • Randers, Central Denmark Region, Danmark, 8930
        • Department of Emergency Medicine, Regional Hospital Randers
      • Viborg, Central Denmark Region, Danmark, 8800
        • Department of Emergency Medicine, Regional Hospital Viborg

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Restrictive fluid administration

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
Läkemedel: 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.
Aktiv komparator: Usual care (standard care)

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
Läkemedel: 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.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
24-hour crystalloid iv. fluids
Tidsram: 24 hours from randomization
total amount of all administered intravenous, crystalloid fluids within 24 hours of randomization
24 hours from randomization

Sekundära resultatmått

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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Marie Kristine Jessen, MD

Samarbetspartners

Aarhus University Hospital
University of Aarhus
Viborg Regional Hospital
Randers Regional Hospital

Utredare

  • Huvudutredare: Marie K Jessen, MD, Research Center for Emergency Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Denmark

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

3 november 2021

Primärt slutförande (Faktisk)

19 december 2021

Avslutad studie (Faktisk)

19 mars 2022

Studieregistreringsdatum

Först inskickad

11 september 2021

Först inskickad som uppfyllde QC-kriterierna

30 september 2021

Första postat (Faktisk)

13 oktober 2021

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

25 mars 2022

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

24 mars 2022

Senast verifierad

1 mars 2022

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • RECEM0001
  • 2021-000224-35 (EudraCT-nummer)
  • 1-10-72-163-21 (Annan identifierare: The Committee on Health Research Ethics, Central Denmark Region)

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

NEJ

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Nej

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

Prenumerera