SepsisPhase 2REFACED SepsisNCT05076435
Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients
A Phase 2 study testing Isotonic crystalloids in people with Sepsis, run by Marie Kristine Jessen, MD at 3 sites in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Isotonic crystalloids
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 3 sitesDenmark
- Study dates
- 3 Nov 2021to 19 Mar 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 17Show fewer
- 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
- Exclusion Criteria: We will exclude patients fulfilling any of following exclusion criteria:
- ≥ 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
Who cannot join
None listed.
Trial locations and contacts
3 sites in 1 country.
Denmark3 sites
Department of Emergency Medicine, Aarhus University Hospital
Aarhus, Central Jutland, 8200
Department of Emergency Medicine, Regional Hospital Randers
Randers, Central Jutland, 8930
Department of Emergency Medicine, Regional Hospital Viborg
Viborg, Central Jutland, 8800
About this study
Official title: 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.
Read the 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
- Conditions
- Sepsis
- Being tested
- Isotonic crystalloids
- Keywords
- Sepsis, Hypotension, IV fluid therapy, Fluid resuscitation, Emergency Department, Crystalloids
- Medical subject headings
- Sepsis, Hypotension, Emergencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isotonic crystalloidsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Isotonic crystalloids |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-hour crystalloid iv. fluids
total amount of all administered intravenous, crystalloid fluids within 24 hours of randomization
Measured: 24 hours from randomization
Secondary outcomes (7)
Protocol violations
Feasibility measure: Number of patients with major protocol violations
Measured: 24 hours from randomization
Screened-vs.-randomized-ratio
Feasibility measure: Number of patients screened vs included
Measured: Through study completion, an average of 1 year
Time to inclusion
Feasibility measure: Time from admission to inclusion/randomization (hours)
Measured: Through study completion, an average of 1 year
Lost-to-follow-up-rate
Feasibility measure: Number of patients lost to follow up in terms of 24-hour fluids
Measured: 24 hours from randomization
Accumulated serious adverse reactions (SARs + SUSARs)
Feasibility measure: Accumulated serious adverse reactions and events (SAEs + SARs+ SUSARs) within 7 days in-hospital
Measured: 7 days from randomization
Total 24-hour fluids
Total fluids (oral and intravenous) at 24 hours
Measured: 24 hours from randomization
Mortality
In-hospital, 30- and 90-days mortality
Measured: Total of 90-days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2021
- Study start3 Nov 2021
- Primary completion19 Dec 2021
- Study completion19 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marie Kristine Jessen, MD
- Sponsor type
- University, hospital or other
- Collaborators
- University of Aarhus, Aarhus University Hospital, Viborg Regional Hospital, Randers Regional Hospital
- Responsible party
- Sponsor-investigator, Marie Kristine Jessen, MD, University of Aarhus
- Investigators
- Marie K Jessen, MD, Principal investigator, Research Center for Emergency Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05076435
- Sponsor's protocol ID
- RECEM0001
- Other IDs
- 2021-000224-35, 1-10-72-163-21
- Acronym
- REFACED Sepsis
- Status last verified
- Mar 2022
- First submitted
- 11 Sep 2021
- Last updated
- 25 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35652491Jessen 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.
PubMed 35351214
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients - a Multicenter, Randomized Clinical Feasibility Trial (REFACED Sepsis)
- ClinicalTrials.gov ID
- NCT05076435
- Acronym / sponsor ID
- REFACED Sepsis / RECEM0001
- Conditions
- Sepsis
- Keywords
- Sepsis, Hypotension, IV fluid therapy, Fluid resuscitation, Emergency Department, Crystalloids
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 124 participants (actual)
- Lead sponsor
- Marie Kristine Jessen, MDUniversity, hospital or other
- Collaborators
- University of Aarhus, Aarhus University Hospital, Viborg Regional Hospital, Randers Regional Hospital
- Study start
- 3 Nov 2021 (actual)
- Primary completion
- 19 Dec 2021 (actual)
- Study completion
- 19 Mar 2022 (actual)
- First posted
- 13 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Restrictive fluid administration | Experimental | Drug: Isotonic crystalloidsNo 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 |
| Usual care (standard care) | Active comparator | Drug: Isotonic crystalloidsThere 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Unplanned emergency department admission
- Age ≥ 18 years
- Sepsis defined as
- Expected hospital stay > 24 hours as deemed by treating clinician
- Further more the patient must fulfill criteria for enrollment in an acute study according to Danish law
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isotonic crystalloidsTypes 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. | Drug | Restrictive fluid administration, Usual care (standard care) |
Primary outcome
24-hour crystalloid iv. fluids
Time frame: 24 hours from randomization
total amount of all administered intravenous, crystalloid fluids within 24 hours of randomization
7 secondary outcomes
Protocol violations
Time frame: 24 hours from randomization
Screened-vs.-randomized-ratio
Time frame: Through study completion, an average of 1 year
Time to inclusion
Time frame: Through study completion, an average of 1 year
Lost-to-follow-up-rate
Time frame: 24 hours from randomization
Accumulated serious adverse reactions (SARs + SUSARs)
Time frame: 7 days from randomization
Total 24-hour fluids
Time frame: 24 hours from randomization
Mortality
Time frame: Total of 90-days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2022.
- Derived from this study: PubMed 35652491Jessen 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.
- Derived from this study: PubMed 35351214Jessen 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.
- Individual participant dataSharing planned: No
Related trials for Sepsis
Not yet recruitingPhase 2/3
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CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
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A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
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Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
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Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marie K Jessen, MD principal investigator
Research Center for Emergency Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Denmark
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isotonic crystalloids in people with Sepsis, run by Marie Kristine Jessen, MD at 3 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-hour crystalloid iv. fluids (time frame: 24 hours from randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05076435, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2022.